This year, James M Berger, of Johns Hopkins University School of Medicine will return to Harvard to present the Doty Lecture, “Still Unscrambling the Puzzle of Biological Machines: The Replisome Continues to Surprise,” on Thursday, April 10, at 12 pm in Lecture Hall B-103 of the Northwest Building. Nancy Kleckner, the Herchel Smith Professor of Molecular Biology in MCB, will introduce him.
Cellular life is predicated on molecular machines that preserve, express, and propagate genetic information. The physical mechanisms by which disparate classes of biological nano-motors, switches, and timers harvest chemical energy and transform it into appropriate functional output remain poorly understood. Even in long-studied biochemical systems, remarkable and unexpected molecular solutions to solving complex enzymatic and mechanical problems continue to be uncovered.
Doty Lecturer James Berger is the world leader in dissecting these problems to reveal general principles across different systems and over evolutionary time. Among multiple lines of research, Berger’s work currently focuses on two areas: (i) topoisomerases (enzymes that alter DNA topology), with respect to structural dynamics, mechanochemical coupling and links to cancer and cancer treatment, and (ii) the complex multi-component machines that mediate initiation and progression of DNA replication. His lecture will consider this latter subject.
Berger obtained his PhD in 1995 in MCB’s predecessor Department, Biochemistry and Molecular Biology. As a joint PhD student with James Wang (discoverer of the first topoisomerase) and Steven Harrison (structural biologist par excellence, now at HMS), he provided the first crystal structure of the major central portion of DNA Topoisomerase II, thereby allowing to elucidate its fundamental “two-gate” mechanism of action. In 1998, after post-doctoral work with Peter Kim at MIT, Berger joined the faculty at U.C. Berkeley, where he became Professor of Biochemistry and Molecular Biology. In 2013 he migrated to Johns Hopkins University as Professor of Biophysics and Biophysical Chemistry and, recently, Vice-Dean for Basic Research.
Paul Doty was the Mallinckrodt Professor of Biochemistry Emeritus and also Director, Emeritus, of the Belfer Center for Science and International Affairs, which he founded at the John F. Kennedy School of Government in 1974. As a biochemist, Doty elucidated the structure and function of large molecules, ranging from the polymers in plastics and fibers, to polypeptides and polynucleotides. He is perhaps best known for demonstrating the denaturation of the double-stranded DNA molecule and its reuniting through hybridization, a technique that helped open the era of recombinant DNA research.
As an advocate for arms control, Doty led and participated in many initiatives to bring Russian and American scientists together in pursuit of international security, making more than 40 trips to the Soviet Union. He was a member of the President’s Science Advisory Committee (PSAC) during the Kennedy Administration. After retirement, he continued his work in this area, including serving as a board member of the Soros International Science Foundation that provided critical research support to Russian scientists in the 1990s. He passed away on December 5, 2011.
Paul Mead Doty (1920-2011) Science Retrospective, PDF
by Matthew Meselson
