Roger Y. Tsien
Wolf Prize Laureate in Medicine 2004
Roger Y. Tsien
Affiliation at the time of the award:
University of California San Diego, USA
“for his seminal contribution to the design and biological application of novel fluorescent and photolabile molecules to analyze and perturb cell signal transduction”.
Professor Roger Y. Tsien has made unique contributions to two major areas of research, biomolecular engineering and signal transduction. Biomolecular engineering is the rational design, synthesis, and improvement of artificial molecules to interact with or modify biological systems in a controlled manner. Tsien’s contributions began with the rational design and synthesis of extremely useful calcium chelators and indicators for intracellular applications. His group pioneered, or improved, biologically useful indicators for sodium and for cAMP, membrane potential indicators, chelators that release or take up Ca2+ upon photoactivation, organic molecules to release nitric oxide intracellularly upon photoactivation, a general approach to making membrane-permeant, extracellularly-effective derivatives of phosphate-containing intracellular messengers and caged molecules that can perturb signal transduction with unprecedented three-dimensional spatial resolution.
He is also a leader in protein engineering, particularly in understanding and improving the Green Fluorescent Protein (GFP), a remarkable macromolecule that spontaneously synthesizes a fluorophore inside itself and thus enables strong visible fluorescence to be encoded genetically. Most of the huge number of applications of GFP in cell biology use mutations discovered in Prof. Tsien’s lab, to confer improved spectral properties, or altered colors. His group has used pairs of differently colored GFPs to build transfectable fluorescent indicators of cytosolic and organellar Ca2+ and to monitor dynamic protein-protein interactions in individual live cells. Prof. Tsien’s fluorescent indicators enable ultra-high-throughput the screening of large numbers of candidate compounds on mammalian cells. These are revolutionizing the pharmaceutical drug discovery process.
Tsien is also a leader in the cell biology signal transduction. His major accomplishments in this area include: the first direct measurements of the important increase in cytosolic free Ca2+ associated with immune cell activation secretion and the cell cycle; pioneer investigations on the occurrence and mechanism of Ca2+ oscillations; evidence that a major function of such oscillations may be to optimize gene expression; the discovery that intracellular Ca2+ gradients (and perhaps localized protein kinase C activation) may predict and control the directionality of toxin secretion from cytotoxic T lymphocytes. Elucidation of primary intracellular signaling pathways, involving synergism between nitric oxide, cGMP and Ca2+ for the induction of cerebellar long-term depression, one of the most important cellular models for mammalian synaptic plasticity.