Arthur L. Horwich
Yale School of Medicine and Howard Hughes Medical Institute
2020 Breakthrough Prize in Life Sciences
For discovering functions of molecular chaperones in mediating protein folding and preventing protein aggregation.
I am thrilled to receive a Breakthrough Prize with my collaborator Ulrich Hartl, celebrating basic research. A miraculous mutant in single-celled baker’s yeast led to the discovery of an unexpected machine of Nature, that assists proteins to fold to their active forms. I’m grateful to my parents who nurtured my love of science with books and ham radio parts; my mentors, Mike Czech, Tony Hunter, Walter Eckhart and Leon Rosenberg, for teaching me how to design, execute and interpret experiments. With Mike I learned one fall morning in 1972 about Christian Anfinsen’s indelibly beautiful experiment observing spontaneous refolding of ribonuclease. I could never have imagined adding kinetic help mediated by a molecular machine to that picture. I thank my collaborators Helen Saibil, Paul Sigler and Kurt Wüthrich for helping bring it all to light, and my wonderful students, postdocs and other collaborators. To name a few, Ming Cheng found the yeast mutant, Kerstin Braig grew the first well-diffracting GroEL crystal, Zbyszek Otwinowski solved that crystal form, and Jonathan Weissman and Hays Rye dissected the reaction cycle. I’m grateful to Wayne Fenton and Krystyna Furtak, 35 years of hands on the experiments, and to my family, my wife Martina, and Mikey, Annie and Dave, who have supported me unwaveringly.