Linda Buck_生物行

Dr. Linda Buck

Fred Hutchinson Cancer Research Center
Basic Sciences Division
Full Member

Howard Hughes Medical Institute
Investigator

University of Washington
Physiology and Biophysics
Affiliate Professor

Mailing Address
1100 Fairview Ave. N, A3-020
Seattle, Washington 98109-1024
United States
Contact Information
Phone: (206) 667-6316
Fax: (206) 667-1031
lbuck@fhcrc.org

Qualifications
Professor, Harvard Medical School, Neurobiology
Ph.D., University of Texas Southwestern Medical Center at Dallas, Immunology
Postdoctoral Fellow, Columbia University, Neurobiology, Molecular Biology

Expertise and Research Interests
THE SENSING OF ODORS AND PHEROMONES

Humans and other mammals can detect thousands of different chemicals present in the external environment. These chemicals are perceived as odors or tastes, or they act as pheromones, stimulating specific behaviors or physiological effects in conspecifics. The discriminatory power of the olfactory system is immense. Even a slight change in the structure of an odorant can alter its perceived odor, for example, from orange to sweaty.

How do mammals detect such an enormous diversity of chemicals-and how does the brain translate those chemicals into perceptions and behaviors? To explore these questions, we have used a combination of molecular, genetic, and cellular approaches to first determine the molecular bases of chemosensory detection and then examine how chemosensory stimuli are represented, or encoded, in the brain.

In initial studies, we identified the odorant receptor (OR) family, a family of ~1000 different receptors that are responsible for detecting odorants in the nose. In later studies, we found three smaller chemosensory receptor families, one for pheromones, one for bitter tastes, and one for sweet tastes. In addition to providing insight into the molecular basis of olfactory and taste detection, these receptor families have provided molecular tools for exploring the neural mechanisms underlying perception.

Our experiments indicate that the OR family is used in a combinatorial fashion to encode odor identities. Each OR detectsnumerous odorants, but different odorants are recognized by different combinations of ORs. Changing the concentration of an odorant, or slightly altering its structure, changes its receptor code, providing an explanation for the ability of such changes to alter a chemical's perceived odor.
In other studies, we found that OR inputs are roughly organized into four zones in the nose and then reorganized into a stereotyped sensory map in the olfactory bulb of the brain. To examine odor coding at higher levels of the olfactory system, we developed a genetic method for visualizing neural circuits. Using this technique, we found a quite different sensory map in the olfactory cortex. This map is virtually identical in different individuals. The patterning of OR inputs in the brain provide insight into the way in which chemical stimuli give rise to perceptions, emotions, and memories. We are currently developing new genetic approaches to further elucidate how chemicals are translated into perceptions and to uncover the neural circuits and cells that mediate fear and aggression, responses that can be elicited by odors and pheromones.

THE DETERMINATION OF LIFESPAN

Our lab is also interested in the mechanisms underlying aging and lifespan. We are particularly intrigued by the possibility that there is a central control of lifespan in which a subset of body cells influences aging in the body as a whole. We are taking two approaches to this question. First, we are conducting a high throughput screen for chemicals that extend lifespan in C. elegans, which will be followed by target identification and characterization. Second, we are using genetic tracers in mice to investigate the cellular and molecular mechanisms that regulate one landmark of aging, puberty.

Publications
Malnic B, Godfrey PA, and Buck LB. The human olfactory receptor gene family. Proc. Natl. Acad. Sci. (USA). in press, 2004

Godfrey PA, Malnic B, and Buck LB. The mouse olfactory receptor gene family. Proc. Natl. Acad. Sci. (USA). in press, 2004

Ranganathan R and Buck LB. Olfactory axon pathfinding: who is the pied piper?. Neuron. 35: 599-600, 2002

Zou Z, Horowitz LF, Montmayeur JP, Snapper S, Buck LB. Genetic tracing reveals a stereotyped sensory map in the olfactory cortex. Nature. 414(6860): 173-9, Nov 2001

Sam M, Vora S, Malnic B, Ma W, Novotny MV, Buck LB. Neuropharmacology. Odorants may arouse instinctive behaviours. Nature. 412(6843): 142, Jul 2001

Montmayeur JP, Liberles SD, Matsunami H, Buck LB. A candidate taste receptor gene near a sweet taste locus. Nature Neuroscience. 4(5): 492-8, May 2001

Matsunami H, Montmayeur JP, Buck LB. A family of candidate taste receptors in human and mouse. Nature. 404(6778): 601-4, Apr 2000

Buck LB. The molecular architecture of odor and pheromone sensing in mammals. Cell. 100(6): 611-8, Mar 2000

Malnic B, Hirono J, Sato T, Buck LB. Combinatorial receptor codes for odors. Cell. 96(5): 713-23, Mar 1999

Horowitz LF, Montmayeur JP, Echelard Y, Buck LB. A genetic approach to trace neural circuits. Proceedings of the National Academy of Sciences (USA). 96(6): 3194-9, Mar 1999

Matsunami H, Buck LB. A multigene family encoding a diverse array of putative pheromone receptors in mammals. Cell. 90(4): 775-84, Aug 1997

Berghard A, Buck LB, Liman ER. Evidence for distinct signaling mechanisms in two mammalian olfactory sense organs. Proceedings of the National Academy of Sciences (USA). 93(6): 2365-9, Mar 1996

Berghard A, Buck LB. Sensory transduction in vomeronasal neurons: evidence for G alpha o, G alpha i2, and adenylyl cyclase II as major components of a pheromone signaling cascade. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience.. 16(3): 909-18, Feb 1996

Sullivan SL, Adamson MC, Ressler KJ, Kozak CA, Buck LB. The chromosomal distribution of mouse odorant receptor genes. Proceedings of the National Academy of Sciences (USA). 93(2): 884-8, Jan 1996

Buck LB. Information coding in the mammalian olfactory system. Cold Spring Harbor Symposia On Quantitative Biology. 61: 147-55, 1996

Buck LB. Information coding in the vertebrate olfactory system. Annual Review of Neuroscience. 19: 517-44, 1996

Buck LB. Unraveling chemosensory diversity. Cell. 83(3): 349-52, Nov 1995

Sullivan SL, Bohm S, Ressler KJ, Horowitz LF, Buck LB. Target-independent pattern specification in the olfactory epithelium. Neuron. 15(4): 779-89, Oct 1995

Sullivan SL, Ressler KJ, Buck LB. Spatial patterning and information coding in the olfactory system. Current Opinion in Genetics & Development. 5(4): 516-23, Aug 1995

Ressler KJ, Sullivan SL, Buck LB. Information coding in the olfactory system: evidence for a stereotyped and highly organized epitope map in the olfactory bulb. Cell. 79(7): 1245-55, Dec 1994

Liman ER, Buck LB. A second subunit of the olfactory cyclic nucleotide-gated channel confers high sensitivity to cAMP. Neuron. 13(3): 611-21, Sep 1994

Ressler KJ, Sullivan SL, Buck LB. A molecular dissection of spatial patterning in the olfactory system. Current Opinion in Neurobiology. 4(4): 588-96, Aug 1994

Ressler KJ, Sullivan SL, Buck LB. A zonal organization of odorant receptor gene expression in the olfactory epithelium. Cell. 73(3): 597-609, May 1993

Ngai J, Dowling MM, Buck L, Axel R, Chess A. The family of genes encoding odorant receptors in the channel catfish. Cell. 72(5): 657-66, Mar 1993

Buck LB. The olfactory multigene family. Current Opinion in Neurobiology. 2(3): 282-8, Jun 1992

Buck LB. The olfactory multigene family. Current Opinion in Genetics & Development. 2(3): 467-73, Jun 1992

Buck L, Axel R. A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell. 65(1): 175-87, Apr 1991

Hynes MA, Gitt M, Barondes SH, Jessell TM, Buck LB. Selective expression of an endogenous lactose-binding lectin gene in subsets of central and peripheral neurons. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience.. 10(3): 1004-13, Mar 1990

Weber DA, Buck LB, Delohery TM, Agostino N, Pernis B. Class II MHC molecules are spontaneously internalized in acidic endosomes by activated B cells. The Journal of Molecular and Cellular Immunology : Jmci. 4(5): 255-66; discussion 2, 1990

Weiss KR, Bayley H, Lloyd PE, Tenenbaum R, Kolks MA, Buck L, Cropper EC, Rosen SC, Kupfermann I. Purification and sequencing of neuropeptides contained in neuron R15 of Aplysia californica. Proceedings of the National Academy of Sciences (USA). 86(8): 2913-7, Apr 1989

Buck LB, Bigelow JM, Axel R. Alternative splicing in individual Aplysia neurons generates neuropeptide diversity. Cell. 51(1): 127-33, Oct 1987

Buck L, Stein R, Palazzolo M, Anderson DJ, Axel R. Gene expression and the diversity of identified neurons. Cold Spring Harbor Symposia On Quantitative Biology. 48 Pt 2: 485-92, 1983

Buck LB, Yuan D, Vitetta ES. A dichotomy between the expression of IgD on B cells and its requirement for triggering such cells with two T-independent antigens. 149(4): 987-92, Apr 1979
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