SCOL Project: The Origins of Cellular Life
Our central goal is to define realistic pathways for the emergence of the first cells on the early Earth; our approach to this problem is to find ways of synthesizing simple living cells in the laboratory. During the past five years we have made considerable progress in understanding how simple cellular systems could have arisen spontaneously on the early Earth. For example, we have demonstrated multiple pathways for the growth and division of membrane vesicles, which mimic the cell membrane of primitive cells. We have also made considerable progress towards the copying of short fragments of RNA in a purely chemical manner, i.e., without enzymes, and we have shown that RNA copying chemistry can proceed inside membrane vesicles. However, copying sequences long enough to be useful to a primitive cell remains a formidable challenge, so most of our effort is directed towards solving this puzzle. We are taking a fourfold approach to this problem: first, by developing a more complete picture of the mechanism of RNA copying chemistry, we hope to identify simple and robust means of making the process more efficient; second, by identifying appropriate sources of chemical energy, we hope to keep the copying chemistry running steadily instead of slowing and stopping with time; third, we will explore strategies to enable multiple cycles of replication; and fourth, by exploring alternative genetic polymers, we hope to learn the fundamental requirements for the replication of informational polymers.
Jack Szostak received his B.Sc. from McGill University in Montreal in 1972, and then conducted his graduate research under the supervision of Ray Wu at Cornell University, Ithaca, N.Y., obtaining his Ph.D. in 1977. Szostak moved to the Sidney Farber Cancer Institute and Harvard Medical School in 1979, and then to Massachusetts General Hospital in 1984. During the 1980s he carried out research on the genetics and biochemistry of DNA recombination, which led to the double-strand-break repair model for meiotic recombination. At the same time Szostak made fundamental contributions to our understanding of telomere structure and function and the role of telomere maintenance in preventing cellular senescence. For this work Szostak shared, with Elizabeth Blackburn and Carol Greider, the 2006 Albert Lasker Basic Medical Research Award and the 2009 Nobel Prize in Physiology or Medicine.
In the 1990s Szostak and his colleagues developed in vitro selection as a tool for the isolation of functional RNA, DNA and protein molecules from large pools of random sequences. His laboratory used in vitro selection and directed evolution to isolate and characterize numerous nucleic acid sequences with specific ligand binding and catalytic properties. For this work, Szostak was awarded, along with Gerald Joyce, the 1994 National Academy of Sciences Award in Molecular Biology and the 1997 Sigrist Prize from the University of Bern. In 2000, Szostak was awarded the Medal of the Genetics Society of America, and in 2008 Szostak received the Dr. H.P. Heineken Prize in Biophysics and Biochemistry.
From 2000 to the present, Szostak’s research interests have focused on the laboratory synthesis of self-replicating systems and the origin of life. For this work he received the Harold Urey Medal from the International Society for the Study of the Origin of Life in 2011.
Szostak is an Investigator of the Howard Hughes Medical Institute, professor of genetics at Harvard Medical School, professor of chemistry and chemical biology at Harvard University, and the Alex Rich Distinguished Investigator in the Department of Molecular Biology and the Center for Computational and Integrative Biology at Massachusetts General Hospital. Szostak is a member of the National Academy of Sciences and the American Philosophical Society, and a fellow of the New York Academy of Sciences, the American Academy of Arts and Sciences and the American Association for the Advancement of Science.