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A nobel experience - Brian Kobilka gets the royal treatment


A nobel experience

Brian Kobilka gets the royal treatment

On Brian Kobilka’s display is a model of one of the body’s most important proteins. Discovering this structure won him the Nobel.

Dear friends and family,

Seasons greetings from the Kobilkas and best wishes for a prosperous and fruitful New Year!

Thus begins the Kobilka family’s annual Christmas letter, an unusually eventful one this year.

In addition to the accomplishments of the two adult children —Megan running two 50-mile races and Jason taking up adult ice hockey in a San Jose league — there was also an engagement announcement for Megan (photo of the gorgeous ring included) and an announcement of Jason’s new software start-up plans.

But Dad managed to beat out even Megan’s engagement for top billing: Huge news this year dropped on us in the form of an early morning phone call (2:30 a.m.!) from Sweden in October, writes Jason, the letter writer this year, in the first paragraph.

The Swedish Royal Academy of Sciences decided that this year, Brian Kobilka would share the 2012 Nobel Prize in Chemistry with his erstwhile mentor Bob Lefkowitz (a professor at Duke University), in recognition of their extensive and invaluable body of work with GPCRs.

It was quite a Christmas letter yet it barely touched on the highlights of the whirlwind three months beginning very early on Oct. 10, 2012, when Brian Kobilka, MD, a 57-year-old physician-turned-dogged-researcher, finally picked up the phone in the dark of his Palo Alto bedroom. (He and his wife, Tong Sun Kobilka, assumed the first attempt to call them was a wrong number and ignored it.) The award led to $600,000 prize winnings and VIP treatment including meeting President Obama and hobnobbing with Supreme Court justices before going to Stockholm where they were escorted in a BMW to banquets, and wined and dined with Swedish royalty.

For the Kobilkas — a down-to-earth California family for whom visits to the haberdashery to be fitted for tails and buying ball gowns are rarely on the “to do” list — it was a sudden and dazzling introduction to the world of scientific celebrity. “Surreal” is the word that Tong Sun, also a physician and scientist, most often uses, a “never-in her-wildest-dreams” kind of thing. “All the time you are thinking, ‘This is surreal,’” says Tong Sun, who has helped run her husband’s lab since college days. This time she’s referring to meeting President Obama at the White House along with the other American Nobel laureates in November. “The President was just a foot away from us. No one said a word; all these brilliant Nobel laureates were tongue-tied. I was the only one who blurted out, ‘So Mr. President, when are you coming to visit Stanford?’ Then you hear that voice: ‘I will visit. I love Stanford!’”

Here her eyes pop, and she laughs.

And all that was before they ever stepped on the plane to Sweden to accept the award.

Brian and Tong Sun, accompanied by Megan, departed for Stockholm on Dec. 3, arriving the next day. During the flight, Brian was constantly reworking his Nobel lecture. He took the responsibility very seriously, feeling a bit nervous, he says. His goal: to summarize two decades of his work that led to the awarding of the Nobel — in under 30 minutes. He remembers little of the days leading up to the lecture except for his preparation, which stretched to about 30 hours all told.

Four days after arriving, he stepped onto the stage in Stockholm University’s Aula Magna, an arena-style lecture hall, nervous but prepared, facing a crowd of hundreds.

“I’d like to thank the Nobel committee for this great honor,” he said, standing at a podium, a giant screen behind him on the stage showing the first of a series of slides on the structural basis of G-protein-coupled receptor signaling.

“What I’d like to do is give you a brief tour through my lab’s efforts ... at understanding this really interesting signaling process,” Kobilka said into the microphone. “I’ll provide a brief overview of the noncrystallographic approaches to understand structure, then efforts to obtain crystal, then the mechanistic insights we’ve obtained from these structures.”

“More than a week of receptions, lectures and audiences with the Swedish royal family left my parents exhausted, itching to get back to work, but ultimately elated.”

Kobilka won the Nobel for his work on understanding the structure and function of G-protein-coupled receptors, or GPCRs, a large protein family of receptors that sense molecules outside the cell and convey chemical messages from those molecules into the cell’s interior. They act as molecular switches. Roughly 800 different GPCRs have been identified to date, making them one of the largest families of human proteins. They regulate the beating of our hearts, the workings of our brains and nearly every other physiological process. About 40 percent of all medications also target these receptors.

In 2011, Kobilka and his team were the first to obtain a three-dimensional image of the exact moment a G-protein-coupled receptor clasped its signaling molecule while simultaneously kicking off a cascade of hundreds of reactions inside the cell. To do so, the lab relied on a technique called X-ray crystallography to generate an image that the Nobel committee would eventually call “a molecular masterpiece.” Such knowledge, it’s hoped, will lead to the design of better drugs to activate or inhibit the receptors.

“We knew that this was really exciting work,” says Søren Rasmussen, PhD, assistant professor at the University of Copenhagen and one of two postdocs formerly in Kobilka’s lab who were invited by Brian to join the celebrations in Stockholm. “We also knew it was risky. But the feeling was more like it was just a matter of time before Brian would succeed.”

Kobilka wrapped up his lecture with a photo of his colleagues grinning after generating that long-sought image. As always, he finished his lecture with thanks to his collaborators, his fellow scientists and especially his wife, all vital to the success of the research. “In conclusion we’ve learned a lot about this interaction. There is still a lot we don’t know. .... There is still a lot of work to do in the future.” But, first, there would be a little time to celebrate.

Kobilka family Christmas letter, continued:

Our family and several of my dad’s key collaborators had the privilege of joining the Nobel entourage during the awards ceremony and banquet in Stockholm this December. More than a week of receptions, lectures and audiences with the Swedish royal family left my parents exhausted, itching to get back to work, but ultimately elated. My mother, who has also been instrumental in my dad’s success, also enjoyed her much-deserved share of the limelight, and was seated next to Prince Daniel at the royal banquet. ...

Tong Sun and Brian Kobilka at the Nobel BanquetTong Sun and Brian Kobilka at the Nobel Banquet.
Copyright © The Nobel Foundation 2012
Photo: Orasisfoto1

While Brian may have difficulty remembering, his wife has no problem relating the VIP treatment that started the minute they arrived in Sweden.

“Stockholm from the air looked beautiful with a blanket of sparkling snow,” Tong Sun wrote in an email about flying into the city. “We were met at the exit door by the secretary general of the National Academy of Sciences. There was a separate stairway for us to walk down to the tarmac where the car was parked. Brian was assigned a BMW with a driver by the name of Stefan Lindman. He took us to the VIP area of Arlanda airport where we waited until they collected our luggage. (This is how we should always travel!) Stefan drove us to the Grand Hotel where we were met by the managing director and taken directly to our suite. It is a huge suite overlooking the bay; the bedroom has a sitting and a dining area and it has a connecting study and of course a huge bathroom.”

Day two, Brian had a fitting for his tux, then finished polishing his lecture. Day three, their son, Jason, and his girlfriend arrived. There was a get-together with the laureates and their families in the Nobel Museum. The physics laureate from Colorado was held up in Frankfurt because of the weather; the literature laureate’s arrival was delayed by bad weather in Beijing. But they all eventually made it.

“It was a nice and laid-back gathering,” Tong Sun wrote.

The celebrity treatment continued the entire week — interviews with journalists on public Swedish TV, private tours of museums and castles, sitting for portraits, dinners, receptions with ambassadors. The couple most enjoyed having their entire family together, along with one of Brian’s earliest collaborators at Stanford, Bill Weiss, PhD, professor of structural biology, the two former postdocs and other research partners.

Still, the focus of the week centered on the ceremony awarding the medal and diploma, a grand affair filled with much pomp and circumstance.

The Nobel ceremony is based on a long and formal tradition. Since 1901, the prizes have been presented to the laureates at ceremonies on the same date, Dec. 10, the anniversary of inventor and industrialist Alfred Nobel’s death. The ceremony, as is also traditional, is held at the Stockholm Concert Hall, which is followed by a banquet for about 1,300 people. The Nobel laureates and the Swedish royal family are guests of honor for both events.

It’s a white tie and tails affair for men, long evening gowns for women. This December, the entrance of the royal family, bejeweled and wearing crowns, was announced by a rolling of the drums and a banging of cymbals, and then the laureates marched in. Mozart played in the background.

Kobilka was looking both nervous and proud among the other laureates. “I now ask you to step forward and receive your awards from the king,” the laureates were told. When it was Kobilka’s turn, the announcer stated: “He didn’t believe it was real until after speaking with five people on the phone with Swedish accents. It was definitely real.”

The camera panned to the Kobilka family, beaming from the audience. And after the awards were bestowed, the royal family and the laureates marched off stage to the singing of the Swedish national anthem.

“It’s a tradition that has gone on for Nobel laureates for the past 100 years,” says Rasmussen, one of those beaming in the audience. “You feel like you are part of research history.”

The Nobel diplomaThe Nobel diploma.
Copyright © The Nobel Foundation 2012; Artist: Susanne Jardeback Calligrapher: Annika Rücker Book binder: Ingemar Dackéus Photo reproduction: Lovisa Engblom

Finally, the partying began.

The banquet, a lavish affair, was held in the gigantic Blue Hall of City Hall, which was filled with long, Hogwarts-style banquet tables. Rasmussen remembers feasting on pheasant and poached pear, almond-potato purée and black cherry sorbet, and that it was amazing. The Crown Princess Victoria — a press favorite — looked glamorous in a glittering green gown. Brian, seated next to the princess, was caught on camera often, as was Tong Sun seated next to the princess’s husband, Prince Daniel.

“Both are very nice people,” Tong Sun says. “Prince Daniel was a commoner until he married the princess.”

For Brian, it was the party after the party, the post-banquet affair, that he enjoyed most, finally able to relax. His 14 invited guests, research collaborators, friends and family, congregated in their own room, watched the dancing, marveled at the entertainment and, well, talked about science. “We are scientists, so, yeah, we probably talked about work,” Rasmussen says.

“I really enjoyed the chance to celebrate with friends and family,” Brian says. “We had a room to ourselves and could go out into the party to enjoy the music and food and entertainment. The acrobats were amazing, scaling the windows and walls. No photographers were allowed. We could just relax and enjoy.”

The trip ended with the family back home in Palo Alto — with Christmas and a wedding still to plan.

“We had a room to ourselves and could go out into the party ... . The acrobats were amazing, scaling the windows and walls. No photographers were allowed. We could just relax and enjoy.”

“I’m just a little unused to all of this,” says Brian, at home in his comfortable kitchen, his hands shoved deep in his jean pockets. He’d just returned from walking his son’s big, white dog, Satchel. Already, he’s back to worrying about getting back the results of grant applications and being behind in his research.

Winning the Nobel, while an amazing accomplishment, does not mean the end of worrying about funding, he says. One of the first things he did after hearing of the award was to join other laureates in signing a petition sent to Obama stressing the importance of funding basic science.

He has hurdled his own financial struggles along the path to his Nobel, his main funding source drying up in 2003. But when his lab began to struggle financially, even going into the red, he never once considered quitting. Instead, he did much of the hands-on research himself, worried that he might ruin the careers of his postdocs by setting them to work on “impossible” achievements.

“When things weren’t going well, and we weren’t getting anywhere, we’d pre-celebrate,” Kobilka remembers. Tong Sun would throw a “pre-celebration” party — pizza and beer or coffee and doughnuts in the lab.

It was nice to finally get the post-celebration party.

The Kobilka family Christmas letter, continued:

The Swedish media were all up in my dad’s business as well, even sending a small crew to California to follow and film his day-to-day life. The whole experience left him a bit dazed, like a shy, lanky deer in headlights.

All the pomp and circumstance haven’t slowed the research down at all either. ... We all feel very blessed, and we hope that 2012 has brought you all the same kind of fortune.

Tong Sun, Brian, Megan, Jason, Satchel and Gus (10-pound mini-dachshund Gus and 100-pound mutt Satchel.)


E-mail Tracie White






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