Biologist Randy Schekman Wins Lasker Award for Basic Medical Research

By Genevieve Shiffrar

November 26, 2002

The most prestigious awards for biological scientists, outside of the Nobel Prize, are the Albert Lasker Medical Research Awards given by the Albert and Mary Lasker Foundation. This year, Cell and Developmental Biology Professor Randy Schekman from the Department of Molecular and Cell Biology garnered this high honor for his work in understanding how cells transport proteins beyond their membrane walls to communicate with other cells.

This process, known as secretion, is critical to the functioning of healthy cells. A wide range of diseases, from botulism to Parkinson's, stem from problems in this system. A variety of treatments has been developed or have been improved, and more advances are being made regularly as a result of Professor Schekman's findings. To name two examples, the Chiron Corporation now uses yeast to produce both insulin for diabetes and a vaccine for hepatitis B.

Download a Real Audio* file to hear Randy Schekman describe this research and the future of the Health Sciences Initiative. See also the Bear in Mind: Conversations with the Chancellor site for an annotated version of this discussion.

Professor Schekman, who is also an investigator for the Howard Hughes Medical Institute, shares the Albert Lasker Award for Basic Medical Research with James E. Rothman of the Sloan-Kettering Institute. While Schekman used genetic analyses of yeast to explore secretion, Rothman used biochemical methods on mammalian cells to understand the process. For nearly thirty years, their research has complimented each other in extraordinary ways, such that many of the discoveries of one scientist depended upon previous findings of the other scientist, and vise versa.

Every cell creates thousands of proteins destined for special jobs outside the cell. If secreted from a pancreas cell for example, a protein hormone could signal cells to absorb glucose from blood. We know this protein as insulin. If released by a nerve cell, a neurotransmitter could be intended to affect mood.

But before these proteins serve their functions, each must be assembled in a strict series of steps within the cell. They travel in a number of different containers, known as organelles, where they are modified and sorted for distinct destinations within the cell. Vesicles pinch from the organelles to serve as transport carriers for the proteins. These vesicles detach from one organelle and reattach on the next organelle in the production line or they attach onto the cell's surface membrane for the protein's transfer outside the cell.

While scientists understood this basic paradigm before Randy Schekman and Jim Rothman, these men made more clear how it really works: how the vesicles are constructed, how they know where to go, and how they fuse with other cell parts. These questions are essential, for if anything should go wrong, death of the cell, or of the organism, can result. For example, in a rare form of hemophilia, the vesicles cannot collect a subset of proteins responsible for blood clotting. Without the release of the protein payload, blood clots cannot complete and a small cut can become life threatening.

Exploring secretion from a genetic perspective, Randy Schekman knew that yeast cells exposed to chemicals that cause mutations may acquire genetic abnormalities that would compromise secretion and lead to the cell's death. He and then-graduate student Peter Novick studied cells that were mutant but had not yet died. These cells would die at high temperatures, but would stay alive at lower temperatures. This allowed the researchers to study under an electron microscope the compromised cells. They observed organelles swollen with proteins, unable to transfer their load. From this discovery, Schekman identified the first two genes responsible for secretion.

Schekman found a much easier way to discover additional defective genes than looking for mutants one at a time. He realized that cells with genetic mutations that block secretion would weigh more than normal cells because of the accumulation of unreleased proteins. By spinning yeast cells in a centrifuge, mutant cells fell to the bottom. Through this technique, Schekman and his colleagues were able to identify 21 more genes responsible for secretion, as well as the specific order in which the steps in secretion were achieved.

These discoveries have such profound and far-reaching influence in basic and applied biological studies that it is simply too soon to gauge the full impact of Randy Schekman's work.

Since more than half of the recipients of the Albert Lasker Award for Basic Medical Research later receive the Nobel Prize as well, we should not be surprised if his accomplishments become even more influential to the understanding basic biological processes and the medical treatments for diseases.

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Related Resources:

• Randy Schekman: A passion for yeast (Media Relations)
• UC Berkeley cell biologist receives Lasker Award for cell secretion research important to biotech industry (Media Relations, September 22, 2002)

*Free RealPlayer software to listen to audio files is available from Real Audio.