Nobel pursuit

Oct. 15, 2012, 1:10 a.m.
Nobel pursuit
Brian Kobilka, M.D. co-winner of the 2012 Nobel Prize in Chemistry. (LINDA A. CICERO/Stanford News Service)

“What’s unique about Brian? Genuine Passion.”

Fourth-year graduate student Andrew Kruse works in Brian Kobilka’s lab, where everyone agrees that Kobilka, the recent recipient of the Nobel Prize in chemistry, is a one-of-a-kind.

“Brian does a lot of work in lab himself,” Kruse said, who argued that Kobilka stands out from professors of his caliber because of the time he personally puts into his lab. “He helps with everything, even the more challenging tasks, like harvesting crystals.”

Kobilka and his former postdoctoral advisor, Robert Lefkowitz, were awarded the 2012 Nobel Prize in chemistry on Oct. 10 for their work on G protein-coupled receptors (GPCRs) – a large family of receptor proteins found on the surface of cells. These receptors detect adrenaline, dopamine, serotonin and histamine and then transmit this signal from one part of the body to another.

“They’re really important targets for existing therapeutics…around 40 to 50 percent of current pharmaceuticals work on G protein-coupled receptors,” Kobilka said. “There is this potential for other G protein-coupled receptors to be used therapeutically, so they’ve been targets for drug discovery.”

“Brian always says you have to love your molecule,” said Aashish Manglik, a biophysics graduate student who has been with Kobilka’s lab for two and a half years. He compared Kobilka to the protein he is famous for: the adrenaline receptor beta-adrenergic.

“Brian has a low-key personality; I think the beta-adrenergic receptor is more ‘come on, let’s go.’ He’s very driven, but he’s not over the top,” he said.

Kobilka, who currently serves as chair of the molecular and cellular physiology department at the School of Medicine, made his first major contribution to the study of GPCRs by isolating the gene that codes for the receptor that responds to adrenaline: the beta-adrenergic receptor. This find led to the discovery of the common structural features of all GPCRs.

The career of the man behind the protein began when he was an undergraduate at the University of Minnesota-Duluth (UMD) where he met his wife, Tong Sun Kobilka (nee Thian), through a shared interest in biology.

“We met in my first biology class, basic intro…she was a year older than I was; she was upset because the freshmen got the first pick of the classes,” he recalled. The Kobilkas went on to do research together in a developmental biology lab at UMD. Tong, a physician, now researches in Brian’s lab several days a week.

UMD professors Robert Carlson and Conrad Firling (in whose class Kobilka and Thian first met) collaborated to set up an interdisciplinary program, through which Kobilka went on to receive his Bachelor of Science degrees in biology and chemistry. The program was the first of its kind, and was set up so Kobilka could do interdisciplinary research in chemistry and molecular biology for his honors research project.

Dedicated to his work, Kobilka has other passions as well.

“He cycled from northern Minnesota to the Rockies in less than 10 days,” remembers Firling, Kobilka’s first college biology professor, “and called me collect to tell me about his trip and that he won our bet.”

“I started when I was 14; I went from Minnesota to Yellowstone with a friend,” Kobilka, an avid long-distance cyclist, said. “Nowadays, you wouldn’t let a 14-year-old do something like that.”

At 57, Kobilka still bikes to work through the campus morning traffic. The Kobilkas’ 28-year-old daughter Megan, a Santa Clara University graduate, plans to become a high school English teacher. Their son, Jason, 31, is a Dartmouth graduate who creates apps for Apple products.

Kobilka went on to get his medical degree, cum laude, from Yale University School of Medicine, followed by a residency in internal medicine at Washington University School of Medicine. He then chose to move to research rather than pursue a career in cardiology, becoming a research fellow and eventually an assistant professor at the Duke University School of Medicine. It was at Duke as a postdoctoral student that he isolated the beta-adrenergic receptor coding-gene.

“I pretty much fell in love with the process and the people [in the lab],” Kobilka said. “Clinical medicine was very interesting yet very different in this respect.”

Kobilka wholeheartedly committed to his postdoctoral fellowship at Duke under Lefkowitz, who would later become his longtime collaborator and mentor.

“He had a big impact on my interest in science,” Kobilka said. “My enthusiasm, he had a way of bringing it up. It was a great experience.”

In 1989, Kobilka moved his research to Stanford.

“Stanford has been a really remarkable place. I’m not really sure how I managed to land here but I did,” he said in a press conference on the morning of Oct. 10. “And I was telling someone this morning, I think it was the only place that offered me a job.”

To this, Philip Pizzo, dean of the School of Medicine responded, “Foresight, foresight!”

Kobilka pointed out that the size of his old lab at Duke was much larger than his current one at the Beckman Center on campus. His old lab hosted between 25 and 30 researchers, whereas his current lab hosts 10.

“At Stanford the groups are smaller, but what’s particularly interesting about Stanford is that the Medical School campus and the undergraduate sciences are all together,” he said.

Kobilka made his latest discoveries, including the breakthrough mapping of GPCR structures, at Stanford. In 2011, his team captured an image of this receptor at the exact moment that it is activated by a hormone and sends a signal into the cell.

“I remember the very first time we could see the helices of the receptor,” said William Weis, professor in the School of Medicine and an early collaborator. “That was the most exciting time because then we knew we really had it.”

Far from resting on his Nobel Prize, Kobilka is still looking to pursue the proteins he studied at Duke in the 1980s. He recently submitted a research program project grant “for the support of a broadly based multidisciplinary research program.”

“We’ve just submitted a grant to try and take what we’re learning about structures and develop structure-based approaches for drug discovery.”

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