Richard Axel

Richard Axel (born July 2, 1946, New York City) is an American neuroscientist whose work on the olfactory system won him and Linda B. Buck, a former post-doctoral scientist in his research group, the Nobel Prize in Physiology or Medicine in 2004.

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In their landmark paper published in 1991, Buck and Axel cloned olfactory receptors, showing that they belong to the family of G protein coupled receptors. By analyzing rat DNA, they estimated that there were approximately one thousand different genes for olfactory receptors in the mammalian genome. This research opened the door to the genetic and molecular analysis of the mechanisms of olfaction. In their later work, Buck and Axel have shown that each olfactory receptor neuron remarkably only expresses one kind of olfactory receptor protein and that the input of from all neurons expressing the same receptor is collected by a single dedicated glomerulus of the olfactory bulb.

Born in New York City, New York, Axel graduated from Stuyvesant High School in 1963,^[1] received his A.B. in 1967 from Columbia University, and his M.D. in 1971 from Johns Hopkins University. He returned to Columbia later that year and became a full professor in 1978. Richard Axel is known to be a great aficionado of opera and was referred to as an 'opera addict' by the Nobel prize winner Eric Kandel. Axel attended Joan Sutherland's debut performance at New York's Metropolitan Opera with his high school friend Jerold Brenowitz, who later became a heart surgeon.

During the late 1970s, Axel, along with microbiologist Saul J. Silverstein, and geneticist Michael H. Wigler, discovered a technique of cotransformation, a process which allows foreign DNA to be inserted into a host cell to produce certain proteins. Patents, now colloquially referred to as the "Axel patents", covering this technique were filed for February 1980 and were issued in August 1983. As a fundamental process in recombinant DNA research as performed at pharmaceutical and biotech companies, this patent proved quite lucrative for Columbia University, earning it almost $100 million a year at one time, and a top spot on the list of top universities by licensing revenue. The Axel patents expired in August 2000.

Axel's primary research interest is on how the brain interprets the sense of smell, specifically mapping the parts of the brain that are sensitive to specific olfactory receptors. He holds the titles of University Professor at Columbia University, Professor of Biochemistry and Molecular Biophysics and of Pathology at Columbia University's College of Physicians and Surgeons, and Investigator of the Howard Hughes Medical Institute. He also taught for Duke University's Program in Genetics and Genomics.^[2]

Key Papers

• A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell. 1991 Apr 5;65(1):175-87.

This is the paper in which Linda Buck & Richard Axel first describe the discovery of the odorant receptors, which was the basis for their shared Nobel Prize.

• The transfer and stable integration of the HSV thymidine kinase gene into mouse cells. Cell. 1978 May;14(1):133-41.

• Altering genotype and phenotype by DNA-mediated gene transfer. Science. 1980 Sep 19;209(4463):1414-22.

These are the papers describing DNA transfection, a critical tool for the entire revolution in biology, in which genes can be modified and then stably transferred into cells. This paper was the basis for the "Axel patent" which at one time brought Columbia University as much as $100 million per year.

The rest of the papers are in chronological order

• Presence in human breast cancer of RNA homologous to mouse mammary tumour virus RNA. Nature. 1972 Jan 7;235(5332):32-6.

• Type C virus from cell cultures of chemically induced rat hepatomas. Science. 1972 Dec 8;178(65):1098-100.

• In situ hybridization to study the origin and fate of identified neurons. Science. 1983 Nov 18;222(4625):800-8

• Functional interaction between human T-cell protein CD4 and the major histocompatibility complex HLA-DR antigen. Nature. 1987 Aug 13-19;328(6131):626-9.

• Molecular characterization of a functional cDNA encoding the serotonin 1c receptor. Science. 1988 Jul 29;241(4865):558-64

• A soluble form of CD4 (T4) protein inhibits AIDS virus infection. Nature. 1988 Jan 7;331(6151):82-4.

• Ectopic expression of the serotonin 1c receptor and the triggering of malignant transformation. Science. 1989 Jun 2;244(4908):1057-62.

• Crystal structure of an HIV-binding recombinant fragment of human CD4. Nature. 1990 Nov 29;348(6300):419-26.

• The level of CD8 expression can determine the outcome of thymic selection. Cell. 1992 Jun 26;69(7):1089-96

• The family of genes encoding odorant receptors in the channel catfish. Cell. 1993 Mar 12;72(5):657-66

• Coding of olfactory information: topography of odorant receptor expression in the catfish olfactory epithelium. Cell. 1993 Mar 12;72(5):667-80.

• Spatial segregation of odorant receptor expression in the mammalian olfactory epithelium. Cell. 1993 Jul 30;74(2):309-18

• Allelic inactivation regulates olfactory receptor gene expression. Cell. 1994 Sep 9;78(5):823-34.

• Topographic organization of sensory projections to the olfactory bulb. Cell. 1994 Dec 16;79(6):981-91

• A novel family of genes encoding putative pheromone receptors in mammals. Cell. 1995 Oct 20;83(2):195-206.

• Visualizing an olfactory sensory map. Cell. 1996 Nov 15;87(4):675-86.

• Genes expressed in neurons of adult male Drosophila. Cell. 1997 Feb 21;88(4):459-69.

• Odorant receptors govern the formation of a precise topographic map. Cell. 1998 Apr 3;93(1):47-60.

• A spatial map of olfactory receptor expression in the Drosophila antenna. Cell. 1999 Mar 5;96(5):725-36

• A map of pheromone receptor activation in the mammalian brain. Cell. 1999 Apr 16;97(2):209-20.

• An olfactory sensory map in the fly brain. Cell. 2000 Jul 21;102(2):147-59.

• Genetic ablation and restoration of the olfactory topographic map. Cell. 2000 Nov 10;103(4):609-20.

• A chemosensory gene family encoding candidate gustatory and olfactory receptors in Drosophila. Cell. 2001 Mar 9;104(5):661-73.

• Spatial representation of the glomerular map in the Drosophila protocerebrum. Cell. 2002 Apr 19;109(2):229-41.

• Two-photon calcium imaging reveals an odor-evoked map of activity in the fly brain. Cell. 2003 Jan 24;112(2):271-82

• Axonal ephrin-As and odorant receptors: coordinate determination of the olfactory sensory map. Cell. 2003 Aug 8;114(3):311-22.

• Mice cloned from olfactory sensory neurons. Nature. 2004 Mar 4;428(6978):44-9. Epub 2004 Feb 15

• Odorant receptors on axon termini in the brain. Science. 2004 Jun 4;304(5676):1468.

• Gene switching and the stability of odorant receptor gene choice. Cell, 117, 801–815

• Interchromosomal interactions and olfactory receptor choice. Cell. 2006 Jul 28;126(2):403-13.

References

1. ^ Eisner, Robin (Winter 2005). Richard Axel: One of the Nobility in Science. Columbia University. Retrieved on 2007-10-31.
2. ^ Distinguished Lecture Series. Retrieved on 2007-10-31.