Hershko has been a summer investigator at the Marine Biological Laboratory since 1991. He was drawn to the MBL when he became interested in learning more about the role that ubiquitin plays in the cell division cycle.
"Many important regulators of the cell cycle are degraded in a programmed fashion, which allows the cell cycle to progress," explains Hershko. The first of these proteins, known as cyclin B, was discovered by Tim Hunt, Joan Ruderman, and their colleagues working independently at the MBL in the early 1980s. (Dr. Hunt won the Nobel Prize in 2001 for this discovery.)
By 1989, MBL scientists had developed a means of studying cyclins and the cell cycle in the test tube using the eggs of local surf clams as models. It turned out to be exactly the system that Hershko needed to study what role, if any, ubiquitin played in the process. In collaboration with Robert Palazzo, now at Rensselear Polytechnic Institute, Hershko determined that cyclin is degraded by the ubiquitin system during the cell cycle. Working with Joan Ruderman of Harvard University, he later identified a specific ubiquitin ligating complex that "targets cyclin B for degradation at the end of mitosis"-the final phase of cell division.
Today Hershko is studying that ubiquitin ligating complex in both clam eggs and cultured human cells in hopes of learning even more about cell division in general and cancer more specifically.
"Changes in the mechanisms that control the activity of this complex lead to chromosome instability, and ultimately to cancer," Hershko says. "Thus, work done at the MBL on the mechanisms of cell division in clam eggs may provide novel insights into their aberration in human cancer."
At the MBL, Hershko is also leading an effort to sequence some of the surf clam's active genes-an effort, Hershko says, that is vital to the future of his research. "We are reach
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Contact: Pamela Clapp Hinkle
pclapp@mbl.edu
508-289-7276
Marine Biological Laboratory
6-Oct-2004