Marine Biological Laboratory summer investigator wins Nobel Prize in Chemistry

10/06/04

MBL embryology course alumnus, Irwin Rose, shares award

October 6, 2004-The Royal Swedish Academy of Sciences announced today that Avram Hershko, a summer researcher at the Marine Biological Laboratory in Woods Hole, Massachusetts, had been awarded the Nobel Prize in Chemistry for "the discovery of ubiquitin-mediated protein degradation." Dr. Hershko, a professor of biochemistry at the Technion-Israel Institute of Technology in Haifa, Israel, shares the award with Aaron Ciechanover also of the Technion, and Irwin Rose of the University of California, Irvine. Dr. Rose is an alumnus of the MBL's Embryology course.

This year's Nobel Prize in Chemistry honors the discovery of the ubiquitin system of regulated protein degradation, a fundamental process that influences key cellular events such as the cell cycle, malignant transformation, and responses to inflammation and immunity.

Ubiquitin is a protein found within cells that targets other proteins for elimination. Scientists have long known that all cells manufacture and subsequently discard an array of proteins involved in a variety of cellular processes. Although many scientists over the years have focused their research on learning more about how cells make proteins, until recently few have explored how cells go about discarding proteins, and the impact that process has on disease.

More than twenty-five years ago, Avram Hershko took a road less traveled in science and began studying how cells rid themselves of unwanted or damaged proteins. With the help of his colleagues, Hershko discovered the ubiquitin system and eventually determined that it impacts major physiological processes in the body. Scientists now know that it is involved in regulating cell division, aids in controlling embryonic development, and helps maintain the immune system. It is implicated in a number of diseases as well, including cervical cancer caused by the human papilloma virus. Because it is involved in the body's inflammatory response to invading microbes, it may also play a role in autoimmune diseases.

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 reaching a barrier in our work, unless we obtain this molecular knowledge," he said.

The effort, called the Clam Project, is the first step toward sequencing the entire clam genome, and its goal is to provide scientists with better knowledge of the clam's active DNA. Such information is crucial to the study of the basic cellular processes involved in many diseases. The scientists plan to use the new genetic information to create antibodies. And they hope to begin experiments impossible without those antibodies as soon as the project is complete. "Sequencing the clam genome will be a quantum leap for our research," said Hershko. (Read more about this project at: http://www.mbl.edu/inside/what/news/publications/labnotes/04_spring01.html

Source: Eurekalert & others

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