Asya Rolls

Krill Prize Laureate 2017

Dr. Asya Rolls

Technion – Israel Institute of Technology.

Physiological mechanisms of brain-body interactions.

The philosophical ‘mind-body problem’ examines the relationship between the mind, a mental process, and the body, a physical entity. In modern medicine, this dialog between the mental and physical state has multiple manifestations, for example, the emergence of disease following stress, or recovery in response to placebo treatment. Nevertheless, this fundamental aspect of physiology remains largely unexplored. My laboratory approaches this question by examining neuronal networks underlying specific brain-body interactions. We examine how the activity of specific brain regions, or specific neuronal ensembles correlated with defined emotional states, affects the immune system, the body’s main protective mechanism.

Using this approach, we recently uncovered a novel potential mechanism of the placebo response. For the past 50 years, most clinical trials include a placebo group to control for non-specific effects such as statistical errors, disease ontology, as well as patient expectations. This expectation of the patient for clinical improvement plays a key role in the placebo response, but it is not known how such expectation affects recovery. We used pharmacogenetics (DREADDs), a state of the art tool in neuroscience, to activate the reward system (dopaminergic neurons in the ventral tegmental area) and analyzed the effects on the immune system. We found that reward system activation strengthens the immediate, innate anti-bacterial immune response, as well as enhancing the formation of long-term immunological memory. We further showed that these effects were mediated via the sympathetic nervous system. These findings were recently published in Nature Medicine (Ben Shaanan, 2016), accompanied by a News and Views report in Nature Medicine, and were featured in Nature and Nature Neuroscience. We hypothesized that because natural rewards such as feeding and sex increase exposure to pathogens, coupling such rewarding activities with increased immunity can be of evolutionary benefit.

Our follow up study demonstrated that reward system activation can attenuate tumor growth by over 40%. We showed that these effects were mediated by an enhancement in the anti-tumor immune response, due to altered innervation to the bone marrow, the site of immune cell formation. This study proposes a potential mechanistic insight to extensive epidemiological data indicating that the patient’s mood is correlated with cancer progression (Spiegel, Lancet, 1989; Spiegel, Cancer, 2007). We expect that by uncovering the mechanisms underlying such brain-immune communication, we will be able to define means to harness the therapeutic potential embedded in the brain.

Accordingly, follow up projects in the laboratory are designed to dissect the specific effects of the peripheral nervous system on the immune compartment. We developed three strains of transgenic mice, each allowing us to control -through optogenetics- a different component of the peripheral nervous system, sympathetic, parasympathetic and serotonergic. We can now manipulate the innervation to the gut, bone marrow, lymph nodes and thymus using laser light, uncovering novel modes of communication between the nervous and immune systems.

This research direction builds on my multidisciplinary background, which places me in a unique position to investigate brain regulation of immunity. We expect this study to alter our understanding of brain-body interactions, and to set the stage for novel approaches to analyze how the state of the mind impacts physiology.

The Krill Prize Winners

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Schraga Schwartz

Winner of Krill Prize 2020

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Kfir Blum

Winner of Krill Prize 2020

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Tomer Michaeli

Winner of Krill Prize 2020

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Yuval Filmus

Winner of Krill Prize 2020

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Meirav Zehavi

Winner of Krill Prize 2020

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Idan Hod

Winner of Krill Prize 2020

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Adam Teman

Winner of Krill Prize 2020

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Yasmine Meroz

Winner of Krill Prize 2020

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Yakir Hadad

Winner of Krill Prize 2020

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Yonit Hochberg

Winner of Krill Prize 2020

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Neta Regev-Rudzki

Winner of Krill Prize 2019

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Ofer Firstenberg

Winner of Krill Prize 2019

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Amnon Bar-Shir

Winner of Krill Prize 2019

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Shahar Kvatinsky

Winner of Krill Prize 2019

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Yaron Fuchs

Winner of Krill Prize 2019

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Baruch Barzel

Winner of Krill Prize 2019

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Malachi Noked

Winner of Krill Prize 2019

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Noga Ron-Zewi

Winner of Krill Prize 2019

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Dafna Shahaf

Winner of Krill Prize 2019

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Ori Katz

Winner of Krill Prize 2019

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Itzhak Tamo

Krill Prize Laureate 2018

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Amit Sever

Krill Prize Laureate 2018

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Meital Landau

Krill Prize Laureate 2018

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Charles E. Diesendruck

Krill Prize Laureate 2018

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Yakov Babichenko

Krill Prize Laureate 2018

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Ayelet Erez

Krill Prize Laureate 2018

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Adi Salomon

Krill Prize Laureate 2018

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Elad Gross

Krill Prize Laureate 2018

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Emmanuel Levy

Krill Prize Laureate 2018

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Anat Milo

Krill Prize Laureate 2018

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Avi Shroeder

Krill Prize Laureate 2017

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Carmel Rotchild

Krill Prize Laureate 2017

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Shiri Chechik

Krill Prize Laureate 2017

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Yonatan Dubi

Krill Prize Laureate 2017

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Yoav Goldberg

Krill Prize Laureate 2017

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Zvika Brakerski

Krill Prize Laureate 2017

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Asya Rolls

Krill Prize Laureate 2017

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Nir Bar-Gill

Krill Prize Laureate 2017

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Yossi Buganim

Krill Prize Laureate 2017

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Eilon Shani

Krill Prize Laureate 2017

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Keren Censor-Hillel

Krill Prize Laureate 2016

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Netanel Lindner

Krill Prize Laureate 2016

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Maya Bar Sadan

Krill Prize Laureate 2016

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Jakub Abramson

Krill Prize Laureate 2016

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Itay Halevy

Krill Prize Laureate 2016

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Yossi Yovel

Krill Prize Laureate 2016

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Daniel Deutch

Krill Prize Laureate 2016

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Assaf Rinot 

Krill Prize Laureate 2016

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Lioz Etgar

Krill Prize Laureate 2016

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Dana Reichmann

Krill Prize Laureate 2016

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Eran Ofek

Krill Prize Laureate 2015

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Ido Amit 

Krill Prize Laureate 2015

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Barak Dayan

Krill Prize Laureate 2015

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Natalie Elia Herooty

Krill Prize Laureate 2015

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Oded Rechavi

Krill Prize Laureate 2015

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Alex Retzker

Krill Prize Laureate 2015

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Michael Schapira

Krill Prize Laureate 2015

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Sharon Ruthstein

Krill Prize Laureate 2015

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Uri Shapira

Krill Prize Laureate 2015

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Moran Bercovici

Krill Prize Laureate 2015

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Or Dunkelman

Krill Prize Laureate 2014

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Irit Gat-Viks

Krill Prize Laureate 2014

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Lilach Gilboa

Krill Prize Laureate 2014

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Eran Bouchbinder

Krill Prize Laureate 2014

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Shahal Ilani

Krill Prize Laureate 2014

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Roie Yerushalmi

Krill Prize Laureate 2014

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Daniel Podolsky

Krill Prize Laureate 2014

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Amir Yehudayoff

Krill Prize Laureate 2014

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Nathan Keller

Krill Prize Laureate 2014

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Niv Papo

Krill Prize Laureate 2014

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

David Nicolas Waldmann

Krill Prize Laureate 2013

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Tomer Volansky

Krill Prize Laureate 2013

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Nirit Dudovich

Krill Prize Laureate 2013

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Anat Levin

Krill Prize Laureate 2013

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Sagiv Shifman

Krill Prize Laureate 2013

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Itai Ynai

Krill Prize Laureate 2013

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Amit Kanigel

Krill Prize Laureate 2013

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Avinoam Zadok

Krill Prize Laureate 2013

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Jacob Hanna

Krill Prize Laureate 2013

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Jacob (kobi) Gal

Krill Prize Laureate 2013

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Yoel Shkolnisky

Krill Prize Laureate 2012

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Alex Bronstein

Krill Prize Laureate 2012

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Erez Levanon

Krill Prize Laureate 2012

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Amos Tanay

Krill Prize Laureate 2012

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Nachum Ulanovsky

Krill Prize Laureate 2012

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Ido Branslavsky

Krill Prize Laureate 2012

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Gil Alexandrowicz

Krill Prize Laureate 2012

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Louisa Meshi

Krill Prize Laureate 2012

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Amir Amedi

Krill Prize Laureate 2011

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Avishay Gal-Yam

Krill Prize Laureate 2011

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Shai Meiri

Krill Prize Laureate 2011

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Taleb Mokari

Krill Prize Laureate 2011

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Reuven Cohen

Krill Prize Laureate 2011

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Oren Cohen

Krill Prize Laureate 2011

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Yuval Shaked

Krill Prize Laureate 2011

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Ehud Altman

Krill Prize Laureate 2010

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Kinneret Keren

Krill Prize Laureate 2010

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Anne Bernheim

Krill Prize Laureate 2010

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Dan Thomas Major

Krill Prize Laureate 2010

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Eran Halperin

Krill Prize Laureate 2010

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Masha Niv

Krill Prize Laureate 2010

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Julia Kempe

Krill Prize Laureate 2009

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Nathalie Questembert-Balaban

Krill Prize Laureate 2009

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Ilan Koren

Krill Prize Laureate 2009

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Boaz Tsaban

Krill Prize Laureate 2009

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Debbie Lindell

Krill Prize Laureate 2009

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Eli C. Lewis

Krill Prize Laureate 2009

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Shiri Artstein-Avidan

Krill Prize Laureate 2008

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Ido Dagan

Krill Prize Laureate 2008

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Roy Bar-Ziv

Krill Prize Laureate 2008

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Eli Berger

Krill Prize Laureate 2008

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Yuval Dor

Krill Prize Laureate 2008

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Jeff Steinhauer

Krill Prize Laureate 2008

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Zeev Zalevsky

Krill Prize Laureate 2007

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Tal Alexander

Krill Prize Laureate 2007

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Roded Sharan

Krill Prize Laureate 2007

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Dr. Yoav Tsori

Krill Prize Laureate 2007

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Oren Froy

Krill Prize Laureate 2007

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Amir Orian

Krill Prize Laureate 2007

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Leeor Kronik

Krill Prize Laureate 2006

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Tal Pupko

Krill Prize Laureate 2006

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Itamar Simon

Krill Prize Laureate 2006

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Shulamit Levenberg

Krill Prize Laureate 2006

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Dorit Aharonov

Krill Prize Laureate 2006

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Eli Barkai

Krill Prize Laureate 2006

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Oded Regev

Krill Prize Laureate 2005

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Ehud Behar

Krill Prize Laureate 2005

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Yonina C. Eldar

Krill Prize Laureate 2005

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Yoram Louzoun

Krill Prize Laureate 2005

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Deborah Fass

Krill Prize Laureate 2005

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.

Erez Lapid

Krill Prize Laureate 2005

Dr. Eilon Shani 
Tel Aviv University
Scientific Overview:
Plant growth and development is mediated to a large extent by hormones. Plants regulate hormone response pathways at multiple levels including biosynthesis, metabolism, perception, and signaling (1-3). In addition, plants exhibit the unique ability to spatially regulate hormone distribution ( 4, 5). This ability is illustrated most clearly in the case of auxin (!AA). The combined activity of auxin influx and efflux carrier proteins generates auxin maxima and local gradients that inform developmental patterning. The regulation of the cellular localization of PIN-FORMED (PIN) efflux transporters determines the direction of auxin flow from one cell to another ( 6, 7). Until recently, little was known about the transport mechanisms and the distribution patterns of hormones other than auxin. These are exciting days for the plant hormone community as novel gibberellin (GA), abscisic acid (ABA), and cytokinin (CK) transporters have recently been identified (8-14) joining earlier findings on auxin transporters (15, 16), all are members ofNPF, ABC, or PUP families. My research group and others identified the NPFs as the first GA transporter in plants 14• Although our studies suggest that individual NPF and ABC genes have specialized functions, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes. The major reason for this is that plant genomes are highly redundant. There are huge numbers of genes encoding NPF and ABC transporters (53 and 120, respectively, in Arabidopsis) that exhibit high redundancy despite diverse substrate specificity of the encoded proteins. This redundancy, with over 80% of all protein-coding genes belonging to families, illustrates the huge challenge to the field of plant genetics in general and to the study of hormone transport specifically. On top of that, certain transporters, such as some NPFs, can transport multiple hormone substrates (GA, ABA) generating a highly robust system that is unique and interesting but puzzling (J 2, 14, 17). Furthermore, transporters with high specificity for conjugated hormones, which must balance the subcellular active hormone pools, have not been identified.
We plan to address the burning questions that emerge from this recent progress in the field, all of which are challenging due to the functional redundancy of plant hormone transporters: 1) Do closely related NPF and ABC members transport multiple substrates and what is the biological importance of such activity? 2) Why have GA exporters, which must exist to enable the movement of the hormone, not been identified? 3) Are there specialized hormone transporters for conjugated hormones and what is their contribution to the rapid hormone response at tissue and subcellular levels? 4) Do subcellularly localized hormone transporters affect the hormone response and what is subcellular hormone map?
The major goal of the lab goals is to investigate the robust and specialized functions of plant hormone transporter families. In our lab we will are using multiple-targeted artificial microRNAs and CRISPR technology to establish Arabidopsis and tomato populations, respectively, deficient in multiple redundant hormone transporters. First stage, we generated a unique targeted forward genetic approach that bypasses functional redundancy in plants with a dynamic screening range. This allows us to first target the NPF and ABC families in Arabidopsis and tomato. At a second stage, we are using targeted high-throughput screens to identify developmental redundant phenotypes. These loss-of-function phenotypes combined with hormone-mediated physiological assays, analyses of transporter expression patterns and localization, and biochemical transport assays allows us to study NPF and ABC hormone transport mechanisms, identify missing exporters, and evaluate subcellular localization of hormone transporters. Our work in the past three years has identified novel putative GA, CK, IAA and ABA hormone transporters, including CRISPR application in tomato that recovered striking GA-mediated growth defects when six novel GA transporters were knocked out in tomato, thus emphasizing the outstanding strength of our screens. Having the novel CRISPR multiple-targeted platform at our disposal is a significant achievement, since it not only contribute to our understanding of hormone transport mechanisms but will also serve as a scientific breakthrough to overcome functional redundancy in all fields of plant biology and agricultural breeding.
In addition, there is growing amount of evidence suggesting that hormone transporters localized on intracellular compartments actively regulate the subcellular distributions of hormones and hormone intermediate (J 8-20). One of the labs aims is to obtain a deeper understanding of hormones distribution in snbcellular resolution, and address the question of quantitative endogenous hormone levels in different compartments. To profile cellular hormone metabolites within discrete organelles, we are using an innovative strategy to isolate distinct cellular compartments and reveal the complete profiles of active hormone and hormone precursors and conjugates in organelles. This approach will generate the first subcellular hormone localization map and will enable the quantification and characterization of the in vivo activities of known and unidentified subcellular hormone transporters. We believe that our studies will lead to a fuller understanding of hormone transporter functions and specialized subcellular activities.