Arthur L. Horwich
|Authur L. Horwich|
|Institutions||Yale School of Medicine
Howard Hughes Medical Institute
|Alma mater||Brown University|
|Known for||uncovering chaperonin action|
|Notable awards||Hans Neurath Award, Protein Society (2001)
Gairdner International Award (2004)
Stein and Moore Award, Protein Society (2006)
Wiley Prize in Biomedical Science (2007)
Rosenstiel Award (2008)
Louisa Gross Horwitz Prize (2008) Shaw Prize (2012)
Arthur L. Horwich (born 1951) is an American biologist and Eugene Higgins Professor of Genetics and Pediatrics at Yale School of Medicine. Horwich has also been a Howard Hughes Medical Institute investigator since 1990. 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.
Horwich was born in 1951. He grew up in Oak Park, west of Chicago. In 1969, he entered Brown University as part of a new program that combined the undergraduate degree with medical school. 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. He graduated as valedictorian of the first class to complete the combined program. 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. At Salk, he worked in Walter Eckhart's laboratory alongside Tony Hunter and witnessed Hunter's discovery of tyrosine phosphorylation. 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."
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.
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
In 2003, Horwich was elected to the National Academy of Sciences. He received the 2004 Gairdner International Award "for his fundamental discoveries concerning chaperone assisted protein folding in the cell and its relevance to neurodegeneration". He received the 2007 Wiley Prize in Biomedical Science jointly with Franz-Ulrich Hartl, Managing Director of the Max Planck Institute of Biochemistry, "for their significant contribution in protein folding." He received the 2008 Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Science jointly with Franz-Ulrich Hartl "for their pioneering work in the field of protein-mediated protein folding." Also with Hartl, Horwich received the 2008 Louisa Gross Horwitz Prize for Biology or Biochemistry from Columbia University. In 2011, Horwich received the Massry Prize from the Keck School of Medicine, University of Southern California and the Albert Lasker Award for Basic Medical Research jointly with Hartl "for discoveries concerning the cell's protein-folding machinery, exemplified by cage-like structures that convert newly made proteins into their biologically active forms."
He has also received two Protein Society awards - the Hans Neurath Award in 2001 and the Stein and Moore Award in 2006.
- "Arthur L. Horwich". Yale School of Medicine. Retrieved 2008-03-18.
- "Form leads to function". Yale School of Medicine. Retrieved 2008-01-24.
- "Arthur L. Horwich, M.D". Howard Hughes Medical Institute. Retrieved 2008-01-24.
- 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. doi:10.1038/337620a0. PMID 2645524.
- Tinsley H. Davis (2004). "Biography of Arthur L. Horwich". The National Academy of Sciences, USA. Retrieved 2008-01-24.
- 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 (The National Academy of Sciences, USA) 84 (12): 4063–4067. doi:10.1073/pnas.84.12.4063. PMC 305022. PMID 3295876. Retrieved 2008-01-25.
- "2004 winners". The Gairdner Foundation. Archived from the original on 14 December 2007. Retrieved 2008-01-24.
- "Recipients Of 6th Annual Wiley Prize In Biomedical Sciences Announced By Wiley Foundation". Medical News Today. 2007-02-02. Retrieved 2008-01-24.
- "Award Winners 2008". Brandeis University. Retrieved 2008-02-01.
- "2011 Lasker Award Description". The Lasker Foundation. Retrieved 2011-09-12.
- "Past Recipients". The Protein Society. Retrieved 2008-02-01.