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Arthur L. Horwich

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Arthur L. Horwich
Born1951 (age 72–73)
NationalityAmerican
Alma materBrown University
Known foruncovering chaperonin action
Awards
Scientific career
FieldsBiology
Institutions
Notable studentsTapan K. Chaudhuri[1]

Arthur L. Horwich (born 1951) is an American biologist and Sterling Professor of Genetics and Pediatrics at the Yale School of Medicine.[2][3] Horwich has also been a Howard Hughes Medical Institute investigator since 1990.[4] His research into protein folding uncovered the action of chaperonins, protein complexes that assist the folding of other proteins; Horwich first published this work in 1989.[5][6]

For his scientific work Horwich has been awarded the Gairdner International Award (2004), Louisa Gross Horwitz Prize (2008), Lasker Award (2011),[7] Shaw Prize (2012), Albany Medical Center Prize (2016), and Breakthrough Prize (2020). He is a member of the National Academy of Sciences and the American Academy of Arts and Sciences.[8][9]

Early years

Horwich was born in 1951. He grew up in Oak Park, west of Chicago.[10] In 1969, he entered Brown University as part of a new program that combined the undergraduate degree with medical school.[10] During medical school, Horwich studied fat cell metabolism in the laboratory of John Fain. Horwich received his A.B. in biomedical sciences in 1972 and his M.D. in 1975.[2][4] He graduated as valedictorian of the first class to complete the combined program.[10] Horwich went on to do an internship and residency in pediatrics at Yale University. Midway through, Horwich was not sure about an entirely clinical future. After completing his residency, he joined the Salk Institute for Biological Studies in La Jolla, California for a postdoctoral position in molecular biology and virology.[10] At Salk, he worked in Walter Eckhart's laboratory alongside Tony Hunter and witnessed Hunter's discovery of tyrosine phosphorylation.[10] He credits this time with sharpening his skills as a scientist. He said, "Tony taught me the nuts and bolts of thinking about a problem."[10]

Research

In 1981, Horwich moved back to New Haven, Connecticut for a postdoctoral fellowship at Yale University School of Medicine. He worked in the laboratory of Leon Rosenberg.[11]

In 1984, he moved across the hall from Rosenberg's lab to start his own laboratory as an assistant professor in the department of genetics. He still collaborated with members of the Rosenberg laboratory, including Wayne Fenton. As an independent researcher, Horwich asked whether the pathway that imports an enzyme called ornithine transcarbamylase (OTC) into the mitochondria of mammalian cells also could work in yeast. In 1987, during a genetic screen in yeast, Horwich and his colleagues stumbled across a protein folding function inside mitochondria. In the mutant strain, proteins entered mitochondria from the cytosol normally but then misfolded and aggregated. They named the protein encoded by the affected gene HSP60, Heat shock protein 60, because it has a mass of 60 kDa and is produced in larger quantity in response to heat. Hsp60 is found in an 850 kDa double ring assembly, each ring containing 7 copies of Hsp60. Such assemblies, known as chaperonins, also exist in other cellular compartments and are essential components, mediating protein folding under both heat shock and normal conditions.[12]

Since 1987, Horwich and his colleagues have been studying these molecules both in vivo and in vitro, with particular emphasis on the Hsp60 homologue in E. coli known as GroEL. They and others found early on that a chaperonin-mediated folding reaction can be reconstituted in a test tube, and that has enabled structural and functional studies that have begun to explain how chaperonins work.

Awards and honors

He has also received two Protein Society awards – the Hans Neurath Award in 2001 and the Stein and Moore Award in 2006.[21]

References

  1. ^ "Tapan K. Chahudhuri- Chaperone Mediated Protein Folding, Protein Engineering and Molecular Biophysics Group".
  2. ^ a b "Arthur L. Horwich". Yale School of Medicine. Archived from the original on May 30, 2008. Retrieved March 18, 2008.
  3. ^ "Form leads to function". Yale School of Medicine. Archived from the original on May 21, 2008. Retrieved January 24, 2008.
  4. ^ a b "Arthur L. Horwich, M.D". Howard Hughes Medical Institute. Retrieved January 24, 2008.
  5. ^ Cheng, M.Y.; Hartl, F.U.; Martin, J.; Pollock, R. A.; Kalousek, F.; Neupert, W.; Hallberg, E. M.; Hallberg, R. L. & Horwich, A. L. (February 16, 1989). "Mitochondrial heat-shock protein hsp60 is essential for assembly of proteins imported into yeast mitochondria". Nature. 337 (6208): 620–625. Bibcode:1989Natur.337..620C. doi:10.1038/337620a0. PMID 2645524. S2CID 4333381.
  6. ^ Wang, Shirley S. (2009-09-14). "The Nobel Prize Will Go To..." Wall Street Journal. ISSN 0099-9660. Retrieved 2022-02-11.
  7. ^ Zimmer, Carl (2011-09-12). "Horwich Wins Lasker Award by Straddling Science and Medicine". The New York Times. ISSN 0362-4331. Retrieved 2022-02-11.
  8. ^ Davis, Tinsley H. (2004-10-19). "Biography of Arthur L. Horwich". Proceedings of the National Academy of Sciences. 101 (42): 15002–15004. doi:10.1073/pnas.0406924101. ISSN 0027-8424. PMC 524080. PMID 15479759.
  9. ^ Hahamy, Madison (2021-05-04). "14 Yale faculty recently elected to the American Academy of Arts & Sciences". Yale Daily News. Retrieved 2022-02-11.
  10. ^ a b c d e f Tinsley H. Davis (2004). "Biography of Arthur L. Horwich". Proceedings of the National Academy of Sciences. 101 (42): 15002–15004. doi:10.1073/pnas.0406924101. PMC 524080. PMID 15479759.
  11. ^ "Horwich is Higgins Professor of Cellular, Molecular Physiology". Yale
  12. ^ Cheng, M.Y.; Pollock, R.A.; Hendrick, J. P. & Horwich, A. L. (June 15, 1987). "Import and processing of human ornithine transcarbamoylase precursor by mitochondria from Saccharomyces cerevisiae". PNAS. 84 (12): 4063–4067. Bibcode:1987PNAS...84.4063C. doi:10.1073/pnas.84.12.4063. PMC 305022. PMID 3295876.
  13. ^ "2004 winners". The Gairdner Foundation. Archived from the original on December 14, 2007. Retrieved January 24, 2008.
  14. ^ "Recipients Of 6th Annual Wiley Prize In Biomedical Sciences Announced By Wiley Foundation". Medical News Today. February 2, 2007. Retrieved January 24, 2008.
  15. ^ "Award Winners 2008". Brandeis University. Archived from the original on August 20, 2007. Retrieved February 1, 2008.
  16. ^ "2011 Lasker Award Description". The Lasker Foundation. Retrieved September 12, 2011.
  17. ^ "Brown confers nine honorary degrees". Brown University. May 25, 2014. Retrieved May 27, 2014.
  18. ^ "Dr. Paul Janssen Award". Dr. Paul Janssen Award. Retrieved 2022-02-11.
  19. ^ Breakthrough Prize in Life Sciences 2020
  20. ^ Backman, Isabella. "Nakasone Prize Won By Arthur Horwich, MD". medicine.yale.edu. Retrieved 2022-02-11.
  21. ^ "Past Recipients". The Protein Society. Archived from the original on May 13, 2008. Retrieved February 1, 2008.
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