Monday, 23 September 2013 00:00

Of Torpedoes, VAMPs, and the Lasker Award—A talk with Richard Scheller

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scheller2Richard Scheller, 2013 Lasker Basic Medical Research winner:
“I still feel like I’m part of the cell biology community in my heart and my soul.”
Photo credit: Genentech

Big discoveries can turn up in unexpected places, such as neurons of the Pacific electric ray, Torpedo californica. That was the start of Richard H. Scheller's path to the 2013 Albert Lasker Basic Medical Research Award, which he received last week. Along with Thomas C. Südhof of Stanford University, Scheller won for their independent investigations into the regulatory mechanisms of neurotransmitter release.

For Scheller, a longtime ASCB member now at Genentech, his research began at Stanford University in the late 1980s with the Torpedo, a cartilaginous fish that can deliver a 45 volt shock to its prey. Scheller and his colleagues began isolating proteins from its synaptic vesicles. These vesicles are abundant in the electric organ of Torpedo, and are remarkably similar to those in the nerve-muscle junctions in mammals.

Scheller's goal was to understand how neurotransmitter release worked. Among the first proteins they isolated was a tiny one they called the vesicle associated membrane protein (VAMP). Scheller and colleagues published their discovery of VAMP-1 in 1988 in PNAS. Later, they found the partners of VAMP-1, first syntaxin and then SNAP-25, which they isolated in rats in collaboration with James Rothman at Yale.

It turned out that VAMP and its associated proteins act like twist-ties with their binding providing the energy that drives membrane fusion. VAMP-1 on synaptic vesicles and syntaxin and SNAP-25 on the neuronal membrane stick out like facing antennae. When they come in close contact, they wrap around each other and force the two membranes together, dumping neurotransmitters into the nerve synapse.

These proteins, now classified in the SNARE (soluble NSF attachment protein receptor) family, are essential for the release of neurotransmitters. (For an even more detailed account of Scheller's discoveries visit the Lasker Foundation website).

After these discoveries and 19 years as a professor at Stanford, Scheller joined the R&D team at Genentech. "I wanted to do something different and I thought that biology... had come to an age where we could think about disease in very mechanistic terms and drug discovery work would be more like basic science than it had been previously." Genentech was the perfect match, he says.

After 12 years, Scheller is now an Executive Vice President of Genentech, and remains pleased with his career path. "It's much more collaborative here; everyone at Genentech has a single purpose." He particularly loves "unblinding clinical trials... sometimes we find that people on our drug live longer than people who weren't. That's a deeply moving experience."

Despite his second career in industry, Scheller maintains his appreciation for basic science research. "I run R&D at Genentech now, but without NIH-funded work, the translational work would be in the dark ages... I am and will always be a big fan of academic basic discovery, and the funding of that work by the NIH has been the engine that has fueled pipelines of drug companies forever."

One thing Scheller misses about academia is working closely with students, fellows, and techs in the lab. "I run such a large group now that I'm a little further removed from the discoveries than I was when I had a lab at Stanford."

Though Scheller's work is far more translational than when he worked in the cell biology department at Stanford, he is still an active ASCB member and has been since 1992. "I'm a biochemist and a cell biologist, that's who I am... I still feel like I'm part of the cell biology community in my heart and my soul."

Christina Szalinski

Christina is a science writer for the American Society for Cell Biology. She earned her Ph.D. in Cell Biology and Molecular Physiology at the University of Pittsburgh.

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