“I remember walking down the hill to grab breakfast after an overnight fire drill with putting up image plates, shooting X-rays, then fetching the plates and putting them into the Fuji scanner at the F1 beamline … thinking, ‘This is really going to change our understanding of this machine.’”
This is how Arthur Horwich relates the excitement during his first data collection on the GroEL protein at the Cornell High Energy Synchrotron Source. Describing his 20-year scientific adventure with the protein-folding machine in his recent Reflections article in The Journal of Biological Chemistry, Horwich takes readers through the initial discovery of the chaperonin, its structural analyses and elucidation of its mechanism.
After his initial training in pediatrics, followed by work in cell transformation and tumor virology, Horwich went on to explore the protein-import machinery in mitochondria. This quest led him to focus on protein misfolding and to discover how the GroEL/GroES chaperonin system refolded proteins. He recollects how a simple phone call led to the fruitful partnership with Ulrich Hartl (his 2013 ASBMB Herbert Tabor Research Award co-winner) that led to this seminal discovery. In collaboration with Paul Sigler and his group of X-ray crystallographers, Horwich then elucidated the structure of the chaperonin and how it works. Through the years, using techniques like electron microscopy, nuclear magnetic resonance and fluorescence spectroscopy, he has been able to unravel the dynamics of protein folding and watch what happens inside the GroEL/GroES ring.
Horwich also writes of the “willingness, personalities and even foibles” of his team members and collaborators. He credits his mentors — Walter Eckhart, Leon Rosenberg and Tony Hunter — not only for their training but also for being great examples of scientists. He remembers Paul Sigler, who “osmotically taught me crystallography”; Helen Saibil, whose electron microscopy images “stunned and reversed our thinking” on the GroEL mechanism; and the “fearless collaborator” Kurt Wüthrich. He writes about his “experimentally fearless” graduate student Ming Cheng, Zbyszek Otwinowski’s “brilliance and daring,” the “true artist” Kerstin Braig and Jonathan Weissman’s “finicky” pet chameleons. He also gives us a glimpse into the scientific thought camps within his lab and the active scientific discussions that led to the great contributions of the Horwich group. In closing, he says the people who made up his team and collaborators “have been just as much fun as the science of working on the chaperonin system.”
Preethi Chander (firstname.lastname@example.org) earned a Ph.D. in structural biology from Purdue University and completed a postdoctoral fellowship at the National Institutes of Health.