08/19/05

Unraveling the Sense of Smell
Linda Buck, HHMI, Fred Hutchinson Cancer Research Center

Introduction by Gerald Weissmann, New York University School of Medicine


Lecture Abstract:
The mammalian olfactory system can detect and discriminate an immense variety of volatile chemicals. It also detects pheromones that stimulate instinctive behaviors. How do mammals distinguish such a large variety of chemicals? And how are those chemicals translated by the brain into diverse perceptions and behaviors? In initial studies, we identified a multigene family encoding ~1000 different odorant receptors (ORs) in the nose. We later found an unrelated family of ~140 candidate pheromone receptors in the vomeronasal organ, another olfactory structure. We found that odor identities are encoded in a combinatorial fashion, with partially overlapping combinations of ORs detecting, and thereby encoding, different odorants. We also found that the combinatorial OR inputs undergo a series of transformations as odor signals travel from the nose to the olfactory bulb and then to the olfactory cortex. Our studies showed that neurons expressing the same OR are randomly distributed in 4 zones in the nose, but their axons converge at two specific spots in the bulb, creating a stereotyped sensory map in which inputs from different ORs are segregated. In the olfactory cortex, we again found a stereotyped map of OR inputs. However, in sharp contrast to the arrangement in the bulb, different OR inputs appear to overlap in a complex pattern in the cortex. Moreover, single cortical neurons may receive combinatorial input from different ORs, potentially allowing integration of multiple components of an odorant's receptor code.


Linda Buck is an Investigator of the Howard Hughes Medical Institute in the Division of Basic Sciences at Fred Hutchinson Cancer Research Center and an Affiliate Professor of Physiology and Biophysics at the University of Washington. She received a B.S. from the University of Washington and a Ph.D. from the University of Texas Health Medical Center at Dallas, and then did postdoctoral work at Columbia University. She was previously Professor of Neurobiology at Harvard Medical School. Dr. Buck is a Member of the National Academy of Sciences. Her honors include The Takasago Award for Research in Olfaction, The LVMH Moet Science for Art Prize, The Unilever Science Award, The R.H. Wright Award in Olfactory Research, The Lewis S. Rosenstiel Award for Distinguished Work in Medical Research, The Perl/UNC Neuroscience Prize, the Gairdner Foundation International Award, and the 2004 Nobel Prize in Physiology or Medicine.

Gerald Weissmann received his M.D. from New York University (NYU) School of Medicine in 1954 and served post-doctoral fellowships in Biochemistry with Severo Ochoa (NYU) and Cell Biology with Dame Honor Fell (Cambridge). From 1973 to 2000, he served as Director of NYU School of Medicine's Division of Rheumatology and is currently Research Professor of Medicine (Emeritus) and the Director of Biotechnology Study Center at New York University School of Medicine. A former president of the American College of Rheumatology and the Harvey Society, Dr. Weissmann is also a Fellow of the AAAS and the New York Academy of Sciences. He was elected to the Accademia Nazionale dei Lincei (Rome) in 2002. Dr. Weissmann is on the Advisory Board of the Ellison Medical Foundation. He was Co-Founder (with E.C. Whitehead) and a Director of The Liposome Company in Princeton, NJ from 1982 to 2000. Dr. Weissmann has a longtime association with the MBL. He is a former investigator and instructor in the MBL's Physiology Course and is currently an MBL Trustee in the Class of 2005. Some of the honors and awards Dr. Weissmann has received include the Paul Klemperer Medal, New York Academy of Medicine in 1997; the Princeton Liposome Research Award in 1994, the Distinguished Investigator Award from the American College of Rheumatology in 1992; the MBL Centennial Award (with James Wyngaarden and DeWitt Stetten, Jr.) in 1988; the Gruber Cancer Research award (with Emil Frei, III) in 1979; and the Alessandro Robecchi International Prize for Rheumatology in 1972. His seven books of essays range from The Woods Hole Cantata (1985) to The Year of the Genome (2002). Dr. Weissmann lives in New York and has a home in Woods Hole.