| News - Friday, October 12, 2012
Stanford physiologist shares Nobel Prize in chemistry
Medical professor Brian Kobilka honored for work on composition of protein receptors
by Chris Kenrick
As Stanford leaders basked in the university's 27th Nobel Prize Wednesday, the winner, physiologist Brian Kobilka, said he was "surprised to be honored because so many people have contributed to things I've done."
Kobilka, a Palo Alto resident who chairs molecular and cellular physiology at Stanford Medical School, shared the chemistry prize for his work on G-protein-coupled receptors, which convey chemical messages across cell membranes. The co-recipient is his former mentor, Duke University professor Robert Lefkowitz, with whom he worked at Duke in the 1980s.
Made of protein, the receptors sit embedded in the cell membrane, with a portion sticking out on each side of the membrane. On the exterior side, the receptor forms a small trench in the membrane that can bind to a specific signal, such as a hormone or neurotransmitter.
When a signal binds the outside of the receptor, the receptor changes shape and a "factory" of signal molecules switches on. The process regulates heartbeat, workings of the brain and nearly every other physiologic function. Forty to 50 percent of all medications target the receptors, Kobilka said.
Kobilka, 57, and Lefkowitz, 69, worked to identify one G-protein-coupled receptor family member called the beta-adrenergic receptor. Kobilka was able to isolate the gene for the receptor to learn more about its composition.
In what he called a "eureka moment" in 2011, Kobilka and his team were the first to obtain a three-dimensional image of another receptor family member bound to its signaling molecule.
"It was so exciting to see this three-dimensional structure and finally know how these transmembrane regions interact during signaling," he said.
Kobilka credited the many people he's worked with through the years, including his wife, Kaiser physician Tong Sun Kobilka. The couple has two grown children, Jason and Megan.
"It's been a collaborative effort with researchers from around the world. I consider that this award recognizes their work as well," Kobilka said.
Kobilka graduated from the University of Minnesota at Duluth and earned an MD from Yale University in 1981, joining the Lefkowitz laboratory in 1984. Early in his career, Lefkowitz used radioactivity to understand the receptors' function and their shape in the cell wall.
Kobilka came to Stanford in 1989 from Duke to join the then-nascent Department of Molecular and Cellular Physiology.
"It was probably the only place that offered me a job," said Kobilka, who recalls himself as a "good, but not exceptional" student.
He said the proximity of Stanford Medical School to colleagues working in physics, chemistry and engineering has helped his work.
"Being at Stanford you attract really fantastic colleagues and students and postdocs. I can't tell you how many times I've thought, 'How am I going to hide the fact that I know this kid is smarter than I am and try to make him think I know something?'"
Science is hard, he said, but it's a "fantastic way to spend your life. If you persevere, you can be successful. As you go from being that young scientist to being an old scientist, you're surrounded by young people with great ideas and enthusiasm and energy, so you still feel young at any age."
At a press conference Wednesday, Oct. 10, Stanford President John Hennessy and Stanford Medical School Dean Philip Pizzo said the Nobel Prize was an affirmation of Stanford's commitment to basic science research.
"Brian's work stands at the crossroads between chemistry, structural biology and molecular medicine," Pizzo said.
"His commitment to staying focused on a problem of extraordinary complexity and to find the techniques and technologies to solve the protein's structure and function is also a testament to the value of investigator-initiated, basic science research. In a day when big teams and massive labs have become the common mediator of modern science, Brian Kobilka represents how a small group of committed scientists can illuminate deep mysteries and open doors to new solutions that will ultimately improve human life."
Of Stanford's 27 Nobel Prize winners, 17 are still living, including four from the medical school. Besides Kobilka they are Paul Berg, chemistry, 1980; Andrew Fire, physiology or medicine, 2006; and Roger Kornberg, chemistry, 2006.
Staff Writer Chris Kenrick can be emailed at ckenrick@paweekly.com. | 
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