Tsien, Roger
Chemical biology; design, synthesis, and application of molecular probes of biological function
Chemical biology; design, synthesis, and application of molecular probes of biological function
Contact Information
Professor of Chemistry and Biochemistry
Professor of Pharmacology
Office: George Palade Labs 310
Phone: 858-534-4891
Email: rtsien@ucsd.edu
Web: www.tsienlab.ucsd.edu
Group: View group members
Professor of Pharmacology
Office: George Palade Labs 310
Phone: 858-534-4891
Email: rtsien@ucsd.edu
Web: www.tsienlab.ucsd.edu
Group: View group members
Education
1977 Ph.D., University of Cambridge
1972 A.B., Harvard College
1977 Ph.D., University of Cambridge
1972 A.B., Harvard College
Awards and Academic Honors
2003
Todd Visiting Professor of Chemistry, University of Cambridge, England
2003
Konrad Bloch Lectureship, Harvard University
2003
Keith Porter Lectureship, American Society for Cell Biology
2003
Hugh Davson Distinguished Lecturer, American Physiological Society
2002
Max Delbrück Medal, Max Delbrück Centrum für Molekulare Medizin, Berlin
2002
Heineken Prize for Biochemistry and Biophysics, Royal Netherlands Academy of Sciences
2002
Christian B. Anfinsen Award, Protein Society
2002
ACS Award for Creative Invention, American Chemical Society
2000
Pearse Prize, Royal Microscopical Society
2000
Herbert Sober Lectureship, American Society for Biochemistry and Molecular Biology
1998
Elected to the National Academy of Sciences
1998
Elected to American Academy of Arts and Sciences
1998
Award for Innovation in High Throughput Screening, Society for Biomolecular Screening
1995
Gairdner Foundation International Award, Canada
1995
Elected to Institute of Medicine
1995
Basic Research Prize, American Heart Association
1995
Artois-Baillet-Latour Health Prize, Belgium
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.
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.
Primary Research Area
Biochemistry
Biochemistry
Interdisciplinary interests
Biophysics
Cellular Biochemistry
Cellular Biochemistry
Selected Publications
- 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).
- 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).
- 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).
- 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).
- 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).
- 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).
- 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).