Sharp, Phillip A.

▪ American physiologist

in full  Phillip Allen Sharp  

born June 6, 1944, Falmouth, Ky., U.S.

      American molecular biologist, awarded the 1993 Nobel Prize for Physiology or Medicine, along with Richard J. Roberts (Roberts, Richard J.), for his independent discovery that individual genes are often interrupted by long sections of DNA that do not encode protein structure.

      Sharp received a doctorate in chemistry from the University of Illinois at Urbana-Champaign in 1969. In that year he began working at the California Institute of Technology, moving to the Cold Spring Harbor Laboratory in New York in 1971. In 1974 he went to the Massachusetts Institute of Technology (MIT), where he joined the Center for Cancer Research (now the Koch Institute for Integrative Cancer Research) and conducted his prize-winning experiments.

      In 1977 Sharp and his team discovered that the messenger RNA (mRNA) of an adenovirus corresponded to four separate, discontinuous segments of DNA. They found that the segments of DNA that coded for proteins, now called exons, were separated by long stretches of DNA, now called introns, that did not contain genetic information. At the same time, a team working independently under Roberts came up with the same finding. Previously biologists had believed that genes were continuous stretches of DNA that served as direct templates for mRNA in the assembly of proteins; this model was based on studies of prokaryotic organisms such as bacteria. Following the discovery of Sharp and Roberts, it was demonstrated that the discontinuous gene structure is the most common one found in eukaryotes, among which are all higher organisms, including humans.

      In 1978 Sharp cofounded a pharmaceutical company called Biogen Ltd. (now Biogen Idec), which later developed agents to treat hairy-cell leukemia, non-Hodgkin lymphoma, and certain autoimmune disorders. Subsequent studies in the late 1970s and early 1980s, many of them carried out in Sharp's laboratory, showed that DNA transcription initially produces a precursor RNA molecule containing copies of the introns; the final mRNA molecule is produced by the removal of the introns and the splicing together of the exons. A significant proportion of genetic diseases result from mutations that arise during splicing. Biologists also believe that the discontinuous structure of genes may be an evolutionary mechanism, permitting the “reshuffling” of exons and thus the synthesis of new proteins.

      In 1988 Sharp received the Louisa Gross Horwitz Prize for his discoveries relating to RNA splicing. He served as head of the biology department at MIT from 1991 to 1999, when he earned the title Institute Professor at the Koch Institute. Following his work on introns and splicing, he began investigating the role of RNA in controlling genes. Sharp's research had direct implications on the development of new therapeutics, which led to his involvement as cofounder of Alnylam Pharmaceuticals in 2002. From 2000 to 2004 he directed the McGovern Institute for Brain Research at MIT, then returned full time to his position in the Koch Institute. In 2004 Sharp was awarded the National Medal of Science for his research and discoveries based on the application of RNA interference (RNAi) technology to genetic studies in cells. In 2006 he cofounded a small biotechnology company called Magen BioSciences, Inc., which focused on the development of drugs to treat dermatological disorders, such as psoriasis and rosacea.

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