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Roger Tsien Chemical biology; design, synthesis, and application of molecular probes of biological function
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| Contact Information |
| Office: CMM 310 |
| Phone: (858) 534-4891 |
| Fax: (858) 534-5270 |
| Email: rtsien@ucsd.edu |
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| Education and Appointments |
| 1977 |
Ph.D., University of Cambridge
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| 1972 |
A.B., Harvard College
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| Awards and Academic Honors |
| 2003 |
Hugh Davson Distinguished Lecturer, American Physiological Society |
| 2003 |
Konrad Bloch Lectureship, Harvard University |
| 2003 |
Todd Visiting Professor of Chemistry, University of Cambridge, England |
| 2003 |
Keith Porter Lectureship, American Society for Cell Biology |
| 2002 |
ACS Award for Creative Invention, American Chemical Society |
| 2002 |
Christian B. Anfinsen Award, Protein Society |
| 2002 |
Heineken Prize for Biochemistry and Biophysics, Royal Netherlands Academy of Sciences |
| 2002 |
Max Delbrück Medal, Max Delbrück Centrum für Molekulare Medizin, Berlin |
| 2000 |
Herbert Sober Lectureship, American Society for Biochemistry and Molecular Biology |
| 2000 |
Pearse Prize, Royal Microscopical Society |
| 1998 |
Elected to American Academy of Arts and Sciences |
| 1998 |
Elected to the National Academy of Sciences |
| 1998 |
Award for Innovation in High Throughput Screening, Society for Biomolecular Screening |
| 1995 |
Artois-Baillet-Latour Health Prize, Belgium |
| 1995 |
Gairdner Foundation International Award, Canada |
| 1995 |
Basic Research Prize, American Heart Association |
| 1995 |
Elected to Institute of Medicine |
| 1991 |
Young Scientist Award, Passano Foundation |
| 1991 |
W. Alden Spencer Award in Neurobiology, Columbia University |
| 1989 - |
Investigator, Howard Hughes Medical Institute |
| 1983-1986 |
Searle Scholar |
| 1982-1989 |
Appointed to faculty, University of California, Berkeley |
| 1977-1981 |
Research Fellow, Gonville and Caius College, Cambridge |
| 1972-1975 |
Marshall Scholar |
| Research Interests |
We build both small synthetic molecules and genetically encoded macromolecules, preferably working in synergy, to detect and manipulate biochemical signals. Current projects include:
1) Genetically encoded chemosensors: We have created fluorescent sensors of intracellular Ca2+ and of many serine/threonine or tyrosine protein kinase activities by fusing fluorescent proteins with modules that change conformation upon binding Ca2+ or becoming phosphorylated. These sensors open tremendous possibilities for imaging dynamic signal transduction at spatial dimensions ranging from the submicroscopic to entire transgenic organisms. Analogous indicators for redox potential, membrane potential, and synaptic transmitters are under development.
2) Organic synthetic tags targeted by molecular biology: Natural fluorescent proteins are somewhat large and limited in spectroscopic properties. We have shown that a much smaller protein motif containing four cysteines can be specifically labeled in living cells with membrane-permeant small molecules carrying two appropriately spaced arsenic substituents. Such dyes allow pulse-chase determination of the age of individual protein molecules, localization by electron microscopy, and rapid photochemically-induced inactivation. We are pursuing many biological applications as well as developing an independent system involving histidine and Zn2+ rather than cysteines and As(III).
3) Imaging specific mRNAs in intact animals and patients: We are working towards catalytic RNAs that would detect specific mRNAs via highly amplifying, noninvasive nonoptical readouts, eventually to help image and treat tumors that express key cancer-specific mRNAs.
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| Primary Research Area: |
Interdisciplinary Specialties: |
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Biochemistry
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Biophysics
Cellular Biochemistry
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| Selected Publications |
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Genetically Encoded Fluorescent Reporters of Protein Tyrosine Kinase Activities in Living Cells. With A.Y. Ting, K.H. Kain, and R.H. Klemke. Proc. Natl. Acad. Sci. USA 98, 15003 (2001).
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Multicolor and Electron Microscopic Imaging of Connexin Trafficking. With G. Gaietta, T.J. Deerinck, S.R. Adams, J. Bouwer, O. Tour, D.W. Laird, G. Sosinsky, and M.H. Ellisman. Science 296, 503 (2002).
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Partitioning of Lipid-modified Monomeric GFPs Into Membrane Microdomains of Live Cells. With D.A. Zacharias, J.D.Violin, and A.C. Newton. Science 296, 913 (2002).
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New Biarsenical Ligands and Tetracysteine Motifs for Protein Labeling In Vitro and In Vivo: Synthesis and Biological Applications. With S.R. Adams, R.E. Campbell, L.A. Gross, B.R. Martin, G.K. Walkup, Y. Yao, and J. Llopis, J. Am. Chem. Soc. 124, 6063 (2002).
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A New Form of Cerebellar Long-term Potentiation is Postsynaptic and Depends on Nitric Oxide But Not cAMP. With V. Lev-Ram, S.T. Wong, and D.R. Storm. Proc. Natl. Acad. Sci. USA 99, 8389 (2002).
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A Monomeric Red Fluorescent Protein. With R.E. Campbell, O. Tour, A.E. Palmer, P. Steinbach, G.S. Baird, and D.A. Zacharias. Proc. Natl. Acad. Sci. USA 99, 7877 (2002).
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A genetically encoded fluorescent reporter reveals oscillatory phosphorylation by protein kinase C. With J.D. Violin, J. Zhang, and A.C. Newton. J. Cell Biology 161, 899 (2003).
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