Stuart L. Schreiber, Ph.D.-Investigator, Howard Hughes Medical Institute
Dr. Schreiber is also a Professor at Harvard University where he is a Member of the Department of Chemistry and Chemical Biology and an Associate Member of the Department of Molecular and Cellular Biology. He is an Affiliate of the Department of Cell Biology at the Harvard Medical School and a Member of the Graduate Programs in Biophysics at Harvard University and in Immunology at the Harvard Medical School.
The most common way of studying protein function involves making mutations in genes that alter the function of the encoded protein. Insights into cellular protein function have also resulted from studies of cell permeable, organic molecules identified from natural sources and designed and synthesized in the laboratory. These molecules, termed ligands, alter protein function by binding to proteins directly. The Robbins Lectures will present results of studies using such molecules to understand and control intracellular signaling pathways-the chemical genetics approach. These low molecular weight ligands have been used to either activate or inactivate their protein targets. Examples are seen in studies of immunophilin-natural product complexes that led to the identification of calcineurin as a mediator of T cell receptor signaling and of FRAP as a mediator of growth factor receptor signaling. A family of cell permeable ligands that induce intracellular proteins to associate, developed in collaboration with Gerald Crabtree, has been used to regulate protein translocation, gene transcription, and signal transduction (including pathways emanating from the T cell receptor and the apoptosis-inducing fas antigen). Finally, we have been using protein-structure-based combinatorial chemistry to discover cell permeable ligands to any protein target. Such a capability is required in order for chemical genetics to have the broad generality of classical genetics-based methods for studying protein function. The methods we have developed to discover ligands rely heavily on modern asymmetric synthesis. They also rely on a new technique for placing collections of organic molecules, prepared using encoded combinatorial synthesis, and cells in nanoliter samples we call nanodroplets. Ligand discovery in nanodroplets will be discussed as a means to generalize chemical genetics and to strengthen growing bonds between chemistry, biology, and medicine.
"Chemical Approach to Understanding and Controlling the Cellular Function of Proteins", 8:00 p.m., Wednesday, January 22.
"Conditional Inactivation of Signaling Proteins using Chemical Genetics" 4:30 p.m., Thursday, January 23.
"Conditional Activation of Signaling Proteins using Chemical Genetics" 4:30 p.m., Friday, January 24.
"Discovery of Ligands for use in Chemical Genetics" 11:00 a.m., Saturday, January 25.
*The first lecture is for a general audience. All lectures are open to the public. All Lectures to be held in Seaver Auditorium, College Avenue between 6th and 7th Streets
The Fred J. Robbins Lectureship
Pomona College takes great pleasure in presenting the Robbins Lectures for 1997, thirty-sixth in the series established by Mr. Robbins to bring to Pomona College distinguished chemists to discuss their current research.
Mr. Robbins' interest in founding the lectureship came in part from his career as a metallurgical engineer and in part from his interest in creative research which developed in his capacity as Chairman and President of a major specialty steel company.
ROBBINS LECTURERS
1962 MELVIN CALVIN Photosynthesis
1963 PETER DEBYE The Nature of Molecular Forces
1964 DAVID GREEN Mitochondrion and Membrane Systems
1965 FRANCIS CRICK The Structure of DNA
1966 LINUS PAULING The Structure of the Nucleus
1967 MARSHALL NIRENBERG Deciphering the Genetic Code
1968 JOHN KENDREW The Structure of Proteins
1969 JACQUES MONOD Molecular Biology and the Kingdom of Ideas
1970 MANFRED EIGEN Dynamics of Biological Macromolecules
1971 GEORGE WALD Vision
1972 ARTHUR KORNBERG DNA and Membrane Biochemistry
1973 EFRAIM RACKER Electron Transport Coupled Phosphorylation
1974 GERALD EDELMAN Molecular Immunology
1975 JULIUS AXELROD Neurotransmitters
1976 GEORGE PORTER Rapid Kinetics
1977 DAVID BALTIMORE Molecular Genetics
1978 WILLIAM LIPSCOMB Structure and Mechanisms of Enzymes
1979 MAX PERUTZ Hemoglobin
1980 ROSALYN YALOW Radioimmunoassay
1981 CHRISTIAN ANFINSEN Structure and Function of Proteins
1982 SYDNEY BRENNER Genetics of the Nervous System
1983 PAUL BERG Eucaryotic Gene Expression
1984 GABOR SOMORJAI Surface Science of Catalysis
1985 GERALD EDELMAN Sciences of Recognition
1986 ROALD HOFFMAN Bridging Organic and Inorganic Chemistry
1987 HERBERT BROWN Boron in Organic Synthesis
1988 JOSEPH GOLDSTEIN & Revelations from Biochemistry and Human Genetics
MICHAEL BROWN
1989 JEREMY KNOWLES Enzymes
1990 YUAN LEE Chemical Reaction Dynamics
1991 GERTRUDE ELION Chemotherapy - The Search of Selectivity
1992 DONALD CRAM Molecular Recognition in Complexation
1993 HEINRICH ROHRER Science for Our Future
1994 THOMAS R. CECH RNA Catalysis
1995 RICHARD N. ZARE Shedding Light on Chemistry
1996 SHERWOOD ROWLAND The Chemistry of Earth's Atmosphere
1997 STUART L. SCHREIBER Chemical Genetics