Phillip Allen Sharp

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Phillip Allen Sharp
Phillip Sharp HD2007 with Winthrop Sears Medal.jpg
Sharp with the Winthrop-Sears Medal in 2007
Born (1944-06-06) June 6, 1944 (age 79)
Falmouth, Kentucky, U.S.
Alma mater
Spouse
Ann Holcombe
​
(m. 1964)​
Children3
Awards
Scientific career
Fields Biologist
Institutions
Doctoral students
Website web.mit.edu/sharplab
External videos
DNA exons introns.gif
Nuvola apps kaboodle.svg Meet Phillip Sharp: "What we were able to discover was that in human cells and in many other cells of higher-order organisms, the genes come in discontinuous segments", MIT

Phillip Allen Sharp (born June 6, 1944) is an American geneticist and molecular biologist who co-discovered RNA splicing. He shared the 1993 Nobel Prize in Physiology or Medicine with Richard J. Roberts for "the discovery that genes in eukaryotes are not contiguous strings but contain introns, and that the splicing of messenger RNA to delete those introns can occur in different ways, yielding different proteins from the same DNA sequence". [2] [3] [4] [5] [6] [7] He has been selected to receive the 2015 Othmer Gold Medal. [8]

Contents

Sharp's current research focuses on small RNAs and other types of non-coding RNAs. His laboratory works to identify the target mRNAs of microRNAs (miRNAs), and has discovered a class of miRNAs that are produced from sequences adjacent to transcription start sites. His laboratory also studies how miRNA gene regulation functions in angiogenesis and cellular stress. [9] [10] [11] [12]

Biography

Sharp was born in Falmouth, Kentucky, the son of Kathrin (Colvin) and Joseph Walter Sharp. [13] He married Ann Holcombe in 1964, and they have three daughters. [14]

Sharp studied at Union College and majored in chemistry and mathematics, afterwards completing his Ph.D. in chemistry at the University of Illinois at Urbana-Champaign in 1969. [15] Following his Ph.D., he did his postdoctoral training at the California Institute of Technology until 1971, where he studied plasmids. [16] Later, he studied gene expression in human cells at the Cold Spring Harbor Laboratory as a senior scientist under James D. Watson. [16]

In 1974, he was offered a position at MIT by biologist Salvador Luria. [16] He was director of MIT's Center for Cancer Research (now the Koch Institute for Integrative Cancer Research) from 1985 to 1991; head of the Biology department from 1991 to 1999; and founder and director of the McGovern Institute for Brain Research from 2000 to 2004. [15] In 1995, the FBI confirmed that Sharp received a letter from Ted Kaczynski, insinuating that Sharp would become a target of the Unabomber because of his work in genetics, stating that "it would be beneficial to your health to stop your research in genetics." [17]

He is currently MIT Professor of Biology Emeritus and member of the Koch Institute, and was an Institute Professor since 1999. [15] He is also the chair of the advisory board of the MIT Jameel Clinic. [18] [19] Sharp co-founded Biogen, Alnylam Pharmaceuticals, and Magen Biosciences, and has served on the boards of all three companies. [20]

Awards and honors

Phillip Sharp with George W. Bush, at the National Medal of Science awards in 2006. Phillip A Sharp.jpg
Phillip Sharp with George W. Bush, at the National Medal of Science awards in 2006.

In addition to the Nobel Prize, Sharp has won several notable awards, including the 2004 National Medal of Science, [21] the 1999 Benjamin Franklin Medal for Distinguished Achievement in the Sciences of the American Philosophical Society, [22] the Golden Plate Award of the American Academy of Achievement in 1981, [23] and the 1988 Louisa Gross Horwitz Prize from Columbia University together with Thomas R. Cech. [24]

Sharp is an elected member of several academic societies, including the American Academy of Arts and Sciences, [25] the American Association for the Advancement of Science, [26] the National Academy of Sciences, [27] and the Institute of Medicine of the National Academies. [28] He was elected a Foreign Member of the Royal Society (ForMemRS) in 2011. [29] [30] In 2012, he was elected the president of the American Association for the Advancement of Science. [31] He is also a Member and Chair of the Scientific Advisory Board of Fidelity Biosciences Group; a member of the Board of Advisors of Polaris Venture Partners; chairman of the Scientific Advisory Board and member of the Board of Directors of Alnylam Pharmaceuticals; advisor and investor at Longwood and Polaris Venture Funds; a member of the Boards of Directors at Syros Pharmaceuticals and VIR Biotechnology; and member and Chair of the Scientific Advisory Board at Dewpoint Biotechnology.

Pendleton County, Kentucky, Sharp's birthplace, named its current middle school after him.

Other activities

In October 2010 Sharp participated in the USA Science and Engineering Festival's Lunch with a Laureate program where middle and high school students got to engage in an informal conversation with a Nobel Prize-winning scientist over a brown-bag lunch. [32] Sharp is also a member of the USA Science and Engineering Festival's Advisory Board. [33] In 2011, he was listed at #5 on the MIT150 list of the top 150 innovators and ideas from MIT. [34]

He is an editorial advisor to Xconomy, [35] and is a member of the Board of Scientific Governors at The Scripps Research Institute. [36] He has also served on the Faculty Advisory Board of the MIT-Harvard Research Journal and MIT Student Research Association. [15]

Selected publications

See also

Related Research Articles

An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word intron is derived from the term intragenic region, i.e., a region inside a gene. The term intron refers to both the DNA sequence within a gene and the corresponding RNA sequence in RNA transcripts. The non-intron sequences that become joined by this RNA processing to form the mature RNA are called exons.

<span class="mw-page-title-main">Messenger RNA</span> RNA that is read by the ribosome to produce a protein

In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.

<span class="mw-page-title-main">RNA</span> Family of large biological molecules

Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself or by forming a template for the production of proteins. RNA and deoxyribonucleic acid (DNA) are nucleic acids. The nucleic acids constitute one of the four major macromolecules essential for all known forms of life. RNA is assembled as a chain of nucleotides. Cellular organisms use messenger RNA (mRNA) to convey genetic information that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome.

<span class="mw-page-title-main">David Baltimore</span> American biologist (born 1938)

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<span class="mw-page-title-main">Spliceosome</span> Molecular machine that removes intron RNA from the primary transcript

A spliceosome is a large ribonucleoprotein (RNP) complex found primarily within the nucleus of eukaryotic cells. The spliceosome is assembled from small nuclear RNAs (snRNA) and numerous proteins. Small nuclear RNA (snRNA) molecules bind to specific proteins to form a small nuclear ribonucleoprotein complex, which in turn combines with other snRNPs to form a large ribonucleoprotein complex called a spliceosome. The spliceosome removes introns from a transcribed pre-mRNA, a type of primary transcript. This process is generally referred to as splicing. An analogy is a film editor, who selectively cuts out irrelevant or incorrect material from the initial film and sends the cleaned-up version to the director for the final cut.

Gene silencing is the regulation of gene expression in a cell to prevent the expression of a certain gene. Gene silencing can occur during either transcription or translation and is often used in research. In particular, methods used to silence genes are being increasingly used to produce therapeutics to combat cancer and other diseases, such as infectious diseases and neurodegenerative disorders.

<span class="mw-page-title-main">H. Robert Horvitz</span> American biologist

Howard Robert Horvitz ForMemRS NAS AAA&S APS NAM is an American biologist best known for his research on the nematode worm Caenorhabditis elegans, for which he was awarded the 2002 Nobel Prize in Physiology or Medicine, together with Sydney Brenner and John E. Sulston, whose "seminal discoveries concerning the genetic regulation of organ development and programmed cell death" were "important for medical research and have shed new light on the pathogenesis of many diseases".

The RNA-induced silencing complex, or RISC, is a multiprotein complex, specifically a ribonucleoprotein, which functions in gene silencing via a variety of pathways at the transcriptional and translational levels. Using single-stranded RNA (ssRNA) fragments, such as microRNA (miRNA), or double-stranded small interfering RNA (siRNA), the complex functions as a key tool in gene regulation. The single strand of RNA acts as a template for RISC to recognize complementary messenger RNA (mRNA) transcript. Once found, one of the proteins in RISC, Argonaute, activates and cleaves the mRNA. This process is called RNA interference (RNAi) and it is found in many eukaryotes; it is a key process in defense against viral infections, as it is triggered by the presence of double-stranded RNA (dsRNA).

<span class="mw-page-title-main">Richard J. Roberts</span> British biochemist

Sir Richard John Roberts is a British biochemist and molecular biologist. He was awarded the 1993 Nobel Prize in Physiology or Medicine with Phillip Allen Sharp for the discovery of introns in eukaryotic DNA and the mechanism of gene-splicing. He currently works at New England Biolabs.

<span class="mw-page-title-main">Craig Mello</span> American biologist (b.1960)

Craig Cameron Mello is an American biologist and professor of molecular medicine at the University of Massachusetts Medical School in Worcester, Massachusetts. He was awarded the 2006 Nobel Prize for Physiology or Medicine, along with Andrew Z. Fire, for the discovery of RNA interference. This research was conducted at the University of Massachusetts Medical School and published in 1998. Mello has been a Howard Hughes Medical Institute investigator since 2000.

<span class="mw-page-title-main">Andrew Fire</span> American biologist and professor of pathology and genetics

Andrew Zachary Fire is an American biologist and professor of pathology and of genetics at the Stanford University School of Medicine. He was awarded the 2006 Nobel Prize in Physiology or Medicine, along with Craig C. Mello, for the discovery of RNA interference (RNAi). This research was conducted at the Carnegie Institution of Washington and published in 1998.

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Joan Elaine Argetsinger Steitz is Sterling Professor of Molecular Biophysics and Biochemistry at Yale University and Investigator at the Howard Hughes Medical Institute. She is known for her discoveries involving RNA, including ground-breaking insights into how ribosomes interact with messenger RNA by complementary base pairing and that introns are spliced by small nuclear ribonucleic proteins (snRNPs), which occur in eukaryotes. In September 2018, Steitz won the Lasker-Koshland Award for Special Achievement in Medical Science. The Lasker award is often referred to as the 'American Nobel' because 87 of the former recipients have gone on to win Nobel prizes.

An interrupted gene is a gene that contains expressed regions of DNA called exons, split with unexpressed regions called introns. Exons provide instructions for coding proteins, which create mRNA necessary for the synthesis of proteins. Introns are removed by recognition of the donor site and the splice acceptor site. The architecture of the interrupted gene allows for the process of alternative splicing, where various mRNA products can be produced from a single gene. The function of introns are still not fully understood and are called noncoding or junk DNA.

In molecular biology, an exonic splicing enhancer (ESE) is a DNA sequence motif consisting of 6 bases within an exon that directs, or enhances, accurate splicing of heterogeneous nuclear RNA (hnRNA) or pre-mRNA into messenger RNA (mRNA).

<span class="mw-page-title-main">RNA interference</span> Biological process of gene regulation

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<span class="mw-page-title-main">R-loop</span> Three-stranded nucleic acid structure

An R-loop is a three-stranded nucleic acid structure, composed of a DNA:RNA hybrid and the associated non-template single-stranded DNA. R-loops may be formed in a variety of circumstances and may be tolerated or cleared by cellular components. The term "R-loop" was given to reflect the similarity of these structures to D-loops; the "R" in this case represents the involvement of an RNA moiety.

Louise Tsi Chow is a professor of biochemistry and molecular genetics at the University of Alabama at Birmingham and a foreign associate with the National Academy of Sciences, known for her research on the human papillomavirus. Her research contributed to the discovery of gene splicing, and in 1993, her collaborator, Richard J. Roberts, received the Nobel Prize for the research, leading some to assert that Chow should have received the honor as well.

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Phillip D. Zamore is an American molecular biologist and developed the first in vitro system for studying the mechanism of RNA interference (RNAi). He is the Gretchen Stone Cook Professor of Biomedical Sciences and Professor of Biochemistry and Molecular Pharmacology at University of Massachusetts Chan Medical School, located in Worcester, Massachusetts. Zamore is the chair of the RNA Therapeutics Institute (RTI) at UMass Chan Medical School, established in 2009, and has been a Howard Hughes Medical Institute Investigator since 2008. 

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References

  1. ↑ The Official Site of Louisa Gross Horwitz Prize
  2. ↑ "The Nobel Prize in Physiology or Medicine 1993". Nobelprize.org. Nobel Media. Retrieved November 12, 2014.
  3. ↑ Sharp, P (2011). "Q&A: Phillip Sharp on biomedical convergence". Cancer Discovery. 1 (5): 370. doi: 10.1158/2159-8290.CD-ND11-08 . PMID   22586619.
  4. ↑ Musgrave, E (2010). "Advancing science across the disciplines: An interview with Nobel Laureate Phillip A. Sharp, PhD". Clinical and Translational Science. 3 (3): 69–70. doi:10.1111/j.1752-8062.2010.00197.x. PMC   5350715 . PMID   20590673.
  5. ↑ Sharp, P. A.; Sharp, P (2005). "Phillip Sharp discusses RNAi, Nobel Prizes and entrepreneurial science". Drug Discovery Today. 10 (1): 7–10. doi:10.1016/S1359-6446(04)03329-X. PMID   15676292.
  6. ↑ Shampo, M. A.; Kyle, R. A. (2004). "Phillip Sharp--Nobel Prize for discovery of "split genes"". Mayo Clinic Proceedings. 79 (6): 727. doi: 10.1016/s0025-6196(11)62621-9 . PMID   15182083.
  7. ↑ Raju, T. N. (2000). "The Nobel chronicles. 1993: Richard John Roberts (b 1943) Phillip a Sharp (b 1944)". Lancet. 355 (9220): 2085. doi:10.1016/s0140-6736(05)73547-9. PMID   10885388. S2CID   53265935.
  8. ↑ "Othmer Gold Medal". Science History Institute . Retrieved February 4, 2015.
  9. ↑ Autobiography at the Nobel site
  10. ↑ Sharp's Research at MIT Archived December 6, 2006, at the Wayback Machine
  11. ↑ Thackray, Arnold; Brock, David C.; Ashiya, Mona (November 20, 2003). Phillip A. Sharp, Transcript of Interviews Conducted by Arnold Thackray, David C. Brock, and Mona Ashiya at Massachusetts Institute of Technology Cambridge, Massachusetts on 28 January, 29 May, and 20 November 2003 (PDF). Philadelphia, PA: Chemical Heritage Foundation.
  12. ↑ "The Koch Institute: Phillip A. Sharp". ki.mit.edu. Retrieved February 11, 2020.
  13. ↑ "Joseph W. Sharp -- Woodhead Funeral Home, Falmouth, KY". Archived from the original on October 28, 2014. Retrieved October 8, 2013.
  14. ↑ "Phillip A. Sharp - Biographical". Nobelprize.org. Nobel Media AB. Retrieved November 12, 2014.
  15. 1 2 3 4 "Curriculum Vitae - Phillip A. Sharp, Ph.D." Sharp Lab. Retrieved November 12, 2014.
  16. 1 2 3 "Short Bio - Phillip A. Sharp". Sharp Lab. Retrieved November 12, 2014.
  17. ↑ "The Communiques of Freedom Club". The Anarchist Library. Retrieved 2021-06-24.
  18. ↑ "Regina Barzilay, James Collins, and Phil Sharp join leadership of new effort on machine learning in health". MIT News | Massachusetts Institute of Technology. 3 October 2018. Retrieved November 13, 2020.
  19. ↑ "People". J-Clinic. Retrieved November 13, 2020.
  20. ↑ Biogen Idec, Inc. (2008). "Proxy statement for annual meeting of stockholders to be held on June 19, 2008 at 9:00 A.M., local time", 7.
  21. ↑ "The President's National Medal of Science Recipient Details - Phillip A. Sharp". National Science Foundation. Retrieved November 12, 2014.
  22. ↑ "Benjamin Franklin Medal for Distinguished Achievement in the Sciences Recipients". American Philosophical Society . Retrieved November 27, 2011.
  23. ↑ "Golden Plate Awardees of the American Academy of Achievement". www.achievement.org. American Academy of Achievement.
  24. ↑ "The Louisa Gross Horwitz Prize for Biology or Biochemistry". Columbia University Medical Center. Retrieved November 12, 2014.
  25. ↑ "Alphabetical Index of Active Members" (PDF). American Academy of Arts and Sciences. November 5, 2013. Retrieved November 12, 2014.
  26. ↑ "Fellows". American Association for the Advancement of Science. Archived from the original on July 27, 2014. Retrieved November 12, 2014.
  27. ↑ "Phillip A. Sharp". National Academy of Sciences. Retrieved November 12, 2014.
  28. ↑ "Directory: IOM Member - Phillip A. Sharp, Ph.D." Institute of Medicine of the National Academies. Archived from the original on November 12, 2014. Retrieved November 12, 2014.
  29. ↑ "Professor Philip Sharp ForMemRS". London: Royal Society. Archived from the original on October 6, 2015.
  30. ↑ "Royal Society". Royal Society. Retrieved March 20, 2010.
  31. ↑ "Phillip A. Sharp, Molecular Biologist and Nobel Laureate, Chosen to Serve as AAAS President-Elect". American Association for the Advancement of Science. March 13, 2012. Retrieved November 12, 2014.
  32. ↑ "Lunch with a Laureate". Archived from the original on April 21, 2010. Retrieved December 9, 2010.. usasciencefestival.org (2010)
  33. ↑ Furthermore, Sharp participates in the Distinguished Lecture Series of the annual Research Science Institute (RSI), a summer research program for high school students held at MIT. Advisors Archived April 21, 2010, at the Wayback Machine . usasciencefestival.org
  34. ↑ "MIT 150: The Top 50". boston.com. Retrieved November 12, 2014.
  35. ↑ "About". xconomy.com. Retrieved November 12, 2014.
  36. ↑ "Board of Scientific Governors". The Scripps Research Institute. Retrieved November 12, 2014.
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