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NIDCD Grantee Buck Wins Nobel Prize for Clarification of Olfactory System
NIDCD grantee Linda B. Buck, Ph.D., has been awarded the 2004 Nobel Prize in Physiology or Medicine, announced today by the Nobel Assembly at the Karolinska Institute in Stockholm, Sweden. Dr. Buck shares the award with Dr. Richard Axel for their discoveries that clarify how the olfactory system works. Dr. Buck has received more than $3 million in research grant support over a period of more than 10 years from the National Institute on Deafness and Other Communication Disorders (NIDCD), a component of the National Institutes of Health.
Before 1991, the sense of smell was one of the most enigmatic of our senses. The basic principles of recognizing and remembering about 10,000 different odors were not clearly understood, in part because the molecules that detect different odors were not clearly established.
In 1991, Axel and Buck -- who was then a postdoctoral fellow in Axel's lab -- described jointly a very large family of about one 1000 genes that give rise to an equivalent number of olfactory receptor types. These receptors are located on the olfactory receptor cells, which occupy a small area in the upper part of the nasal epithelium.
Axel and Buck have since worked independently of each other, and they have in many elegant studies clarified the olfactory system, from the molecular level to the organization of cells.
Their pivotal discovery that receptor proteins must somehow recognize and bind odorant molecules, thereby stimulating the cell to send signals to the brain, answered several basic questions about olfaction:
- How does the system respond to the thousands of molecules of different shapes and sizes known as odorants?
- Does it use a restricted number of receptors or a large number of relatively specific receptors?
- How does the brain make use of these responses to discriminate between odors?
The string of discoveries that totally changed the study of olfaction resulted from a new emphasis on genetics. Instead of hunting for the receptor proteins directly, Axel and Buck looked for genes that encode receptor proteins found only in the olfactory epithelium. Their efforts produced nothing at first. Finally, Buck came up with what Axel called "an extremely clever twist." She made several assumptions that allowed her to zero in on a group of genes that appear to code for the odorant receptor proteins.
The discovery of mouse olfactory receptor genes has also allowed researchers to isolate and identify the genes for similar receptor proteins in other species by searching through gene libraries of DNA from these species. Odorant receptors from humans, mice, catfish, dogs, and salamanders have been identified based on similarities with mouse odorant receptor genes.
The team's most surprising finding was that there are so many olfactory receptors. The 100 different genes the researchers first identified were just the tip of the iceberg. It now appears that there are between 500 and 1,000 separate receptor proteins on rat and mouse olfactory neurons. Humans appear to have closer to 350 functional olfactory receptor proteins and types of neurons.
"These findings have made it possible to study the sense of smell with the techniques of modern molecular and cell biology and to explore how the brain discriminates among odors," said Dr. James Battey, Director of the National Institute on Deafness and Other Communication Disorders.
Dr. Buck is a principal investigator in the Department of Neurobiology of the Fred Hutchinson Cancer Research Center, Seattle, Washington. Dr. Axel is with the Howard Hughes Medical Institute at Columbia University in New York, New York. Dr. Axel is also a long-term recipient of NIH funding.
The National Institute on Deafness and Other Communication Disorders supports and conducts research and research training on normal and disordered processes of hearing, balance, smell, taste, voice, speech and language.