James E. Rothman was awarded the Dr H.P. Heineken Prize for Biochemistry and Biophysics 2000 for clarifying the mechanism of intracellular membrane fusion.
He made the historic discovery that the cell contains very small membrane-enveloped vesicles that carry a large variety of proteins between different compartments in the cytoplasm. This delivery process, which involves vesicle flow and membrane fusion, is vital for the growth and division of every cell. How this process comes about was a great mystery, and one of the great unsolved questions of biochemistry and cell biology. James Rothman discovered the molecular principles of intracellular membrane fusion and demonstrated that the specificity of fusion was dictated by the pairing of SNARE proteins between membranes. This historic discovery provided a single unified principle for understanding important physiological processes, including the release of insulin into the blood, communication between nerve cells in the brain and the entry of viruses like HIV (the AIDS virus) to infect cells. Defects in the control of these pathways are important in diabetes and most likely also in certain cancers. Currently a major effort is under way to develop a new generation of drugs to control AIDS by blocking the membrane fusion process.
Further reading
Thomas H. Söllner, Sidney W. Whiteheart, Michael Brunner, Hedlye Erdjument-Bromage, Scott Geromanos, Paul Tempst & James E. Rothman: ‘SNAP receptors implicated in vesicle targeting and fusion’, Nature 362, 318 (1993);
Walter Nickel, Thomas Weber, James A. McNew, Francesco Parlati, Thomas H. Söllner & James E. Rothman: ‘Content mixing and membrane integrity during membrane fusion driven by pairing of isolated v-SNAREs and t-SNAREs’, PNAS, 96, (22), 12571 (1999);
B. Brugger, W. Nickel, T. Weber, F. Parlati, J.A. McNew, J.E. Rothman, T. H. Söllner: ‘Putative fusogenic activity of NSE is restricted to a lipid mixture whose coalescence is also triggered by other factors’, EMBO Journal, 19 (6), 1272 (2000).
Biography
James Rothman was born in Haverhill, Massachusetts, USA, in 1950 and is an American citizen. He has a Ph.D. in Biological Chemistry (Harvard Medical School), and has worked at the Sloan-Kettering Institute in New York since 1991. In that same year he was appointed Chairman of the Programme in Cellular Biochemistry and Biophysics at the Memorial Sloan-Kettering Cancer Center, where he holds the Paul A. Marks Chair. Dr Rothman has also been vice-chairman of the Sloan Kettering Institute since 1994. Amongst his other honours, Dr Rothman has received the Gairdner Foundation International Award (1996), the King Faisal International Prize in Science (1996) and the Lounsbery Award of the National Academy of Sciences (1997). In 2013 he won the Nobel Prize in Physiology or Medicine (together with Randy W. Schekman and Thomas C. Südhof).
Video
Video interview with James Rothman, laureate of the Dr H.P. Heineken Prize for Biochemistry and Biophysics 2000