Arthur L. Horwich
Encyclopedia
Arthur L. Horwich 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 chaperonin
s, protein complexes that assist the folding of other proteins. Horwich first published this work in 1989.
, 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."
for a postdoctoral fellowship at Yale University School of Medicine. He worked in the laboratory of Leon Rosenberg.
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.
. 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. In 2011, Horwich received the Albert Lasker Basic Medical Research Award 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.
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
biologist
Biologist
A biologist is a scientist devoted to and producing results in biology through the study of life. Typically biologists study organisms and their relationship to their environment. Biologists involved in basic research attempt to discover underlying mechanisms that govern how organisms work...
and Eugene Higgins Professor of Genetics and Pediatrics at Yale School of Medicine
Yale School of Medicine
The Yale School of Medicine at Yale University is a private medical school located in New Haven, Connecticut, U.S. It was founded in 1810 as The Medical Institution of Yale College, and formally opened its doors in 1813....
. Horwich has also been a Howard Hughes Medical Institute
Howard Hughes Medical Institute
Howard Hughes Medical Institute is a United States non-profit medical research organization based in Chevy Chase, Maryland. It was founded by the American businessman Howard Hughes in 1953. It is one of the largest private funding organizations for biological and medical research in the United...
investigator since 1990. His research into protein folding
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
uncovered the action of chaperonin
Chaperonin
Chaperonins are proteins that fold and unfold other proteins. Newly made proteins usually must fold from a linear chain of amino acids into a three-dimensional form. Chaperonins belong to a large class of molecules that assist protein folding, called molecular chaperones...
s, protein complexes that assist the folding of other proteins. Horwich first published this work in 1989.
Early years
Horwich was born in 1951. He grew up in Oak ParkOak Park, Illinois
Oak Park, Illinois is a suburb bordering the west side of the city of Chicago in Cook County, Illinois, United States. It is the twenty-fifth largest municipality in Illinois. Oak Park has easy access to downtown Chicago due to public transportation such as the Chicago 'L' Blue and Green lines,...
, west of Chicago
Chicago
Chicago is the largest city in the US state of Illinois. With nearly 2.7 million residents, it is the most populous city in the Midwestern United States and the third most populous in the US, after New York City and Los Angeles...
. In 1969, he entered Brown University
Brown University
Brown University is a private, Ivy League university located in Providence, Rhode Island, United States. Founded in 1764 prior to American independence from the British Empire as the College in the English Colony of Rhode Island and Providence Plantations early in the reign of King George III ,...
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.
Bachelor of Arts
A Bachelor of Arts , from the Latin artium baccalaureus, is a bachelor's degree awarded for an undergraduate course or program in either the liberal arts, the sciences, or both...
in biomedical sciences in 1972 and his M.D.
Doctor of Medicine
Doctor of Medicine is a doctoral degree for physicians. The degree is granted by medical schools...
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
Yale University
Yale University is a private, Ivy League university located in New Haven, Connecticut, United States. Founded in 1701 in the Colony of Connecticut, the university is the third-oldest institution of higher education in the United States...
. Midway through, Horwich was not sure about an entirely clinical future. After completing his residency, he joined the Salk Institute for Biological Studies
Salk Institute for Biological Studies
The Salk Institute for Biological Studies is a premier independent, non-profit, scientific research institute located in La Jolla, California. It was founded in 1960 by Jonas Salk, the developer of the polio vaccine; among the founding consultants were Jacob Bronowski and Francis Crick. Building...
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."
Research
In 1981, Horwich moved back to New Haven, ConnecticutNew Haven, Connecticut
New Haven is the second-largest city in Connecticut and the sixth-largest in New England. According to the 2010 Census, New Haven's population increased by 5.0% between 2000 and 2010, a rate higher than that of the State of Connecticut, and higher than that of the state's five largest cities, and...
for a postdoctoral fellowship at Yale University School of Medicine. He worked in the laboratory of Leon Rosenberg.
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
Ornithine transcarbamylase
Ornithine transcarbamoylase is an enzyme that catalyzes the reaction between carbamoyl phosphate and ornithine to form citrulline and phosphate...
(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
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....
normally but then misfolded and aggregated. They named the protein encoded by the affected gene HSP60
HSP60
Heat shock proteins are generally responsible for preventing damage to proteins in response to high levels of heat. Heat shock proteins are classified into six major families based on their molecular mass: small HSPs, HSP40, HSP60, HSP70, HSP90, and HSP110...
, 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 SciencesUnited States National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
. 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
Wiley Prize
The Wiley Prize in Biomedical Sciences is intended to recognize breakthrough research in pure or applied life science research that is distinguished by its excellence, originality and impact on our understanding of biological systems and processes...
in Biomedical Science jointly with Franz-Ulrich Hartl
Franz-Ulrich Hartl
Franz-Ulrich Hartl is a German biochemist and Managing Director of the Max Planck Institute of Biochemistry. He is known for his pioneering work in the field of protein-mediated protein folding....
, Managing Director of the Max Planck Institute of Biochemistry
Max Planck Institute of Biochemistry
The Max Planck Institute of Biochemistry is a research institute of the Max Planck Society located in Martinsried, a suburb of Munich. The Institute was "founded in 1973 by the merger of three formerly independent institutes: the Max Planck Institute of Biochemistry, the Max Planck Institute of...
, "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. In 2011, Horwich received the Albert Lasker Basic Medical Research Award 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.