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. 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 ==