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The receptors, which snake in and out of the cell membrane, serve as one of the main methods of communication within the body — conveying chemical messages into the cell's interior from outside through the membrane. In 2011, Kobilka crystallized one of the receptors bound to its signaling molecule. About 1,000 human genes encode the receptors. They regulate the beating of our hearts, the workings of our brains and nearly every other physiological process. About 40 percent of all medications target these receptors, including Zyprexa, which is used to treat schizophrenia; the antihistamine Clarinex; and Zantac, which is used for stomach ulcers and gastro-esophageal reflux disease. G-protein-coupled receptors are also involved in some kinds of drug addictions, such as addiction to morphine and other opiates. Ironically, one of these receptors recognizes and responds to epinephrine, or adrenaline. "I didn't believe it at first, but after I spoke with about five people — they handed the phone around — with really convincing Swedish accents, I started to think it was for real," said the jean-clad Kobilka, who poured his coffee with shaking hands after the 2:20 am call. "We didn't make it to the phone the first time, we thought it was a wrong number. I'm glad they tried again." Kobilka, 57, who is also the Helene Irwin Fagan Professor at Stanford, shares the $1.2 million prize with his former mentor, Robert Lefkowitz, MD, 69, professor of medicine and of biochemistry at Duke University. They will officially receive the award at a ceremony in Stockholm on Dec. 10. In the 1980s, the two men worked to identify one receptor family member called the beta-adrenergic receptor. Kobilka was able to isolate the gene for the receptor (no small feat at the time) to learn more about its composition. This research helped the scientists realize that G-protein receptors are a large family, with many different examples throughout the body. In 2011, Kobilka and his team were the first to obtain a three-dimensional image of the same G-protein-coupled receptor bound to its signaling molecule — an extremely difficult technical endeavor due to the protein's size and complexity. Knowing the structure is important to be able to design better drugs to activate or inhibit the receptors. "It was so exciting to see this three-dimensional structure and finally know how these trans-membrane regions interact during signaling," said Kobilka. "I hope my discovery leads to better and less-expensive drugs for patients." Kobilka credits the many people he's worked with through the years, including his wife (with whom he works), Tong Sun Kobilka, MD. "I'm particularly surprised to be honored, because so many people have contributed to things that I've done. It's been a collaborative effort with researchers from around the world. I consider that this award recognizes their work as well." "That Brian Kobilka is the 2012 recipient of the Nobel Prize in Chemistry is a tribute to scientific elegance, excellence and endurance, conducted over decades with passion, dedication and commitment," said medical school dean Philip Pizzo, MD. "Trained as an MD, Brian became dedicated to solving deep and important mysteries that impact the work of hearts and minds. When others felt the problem he was attempting to solve was impossible to accomplish, he focused his energies and, over the past decades, he defined the three-dimensional structure of the adrenergic receptor, along with its function and physiological relevance." Kobilka received his MD from Yale University in 1981. In 1984 he joined the Lefkowitz laboratory. 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 has two grown children, Jason and Megan, neither of whom are in science. He and his wife, Tong Sun, have been together since he was an undergraduate student. "She's probably more excited than I am," said Kobilka. "I'm very proud of Brian," said Tong Sun Kobilka. "This is well-deserved." Proteins are linear strings of amino acids that fold into complex and dynamic shapes. G-protein-coupled receptors are also known as seven-trans-membrane receptors because they usually snake in and out of the cell membrane seven times, ending with one end outside the cell and the other inside. As such, they 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. The interior side of each of these receptors is like a small factory. When a signal binds the outside of the receptor, the whole receptor changes shape and the factory inside the cell switches on. The factory makes many new signal molecules, which travel to different parts of the cell's interior and amplify the original signal. "Brian's work stands at the crossroads between chemistry, structural biology and molecular medicine," said Pizzo. "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. "His work is a testament to the importance of supporting basic science research — whose payoff can take many years or decades to reach fruition but, when it does, it changes the direction of medicine and science," said Pizzo. As of today, it's also irrevocably changed Kobilka's life. "I'm not used to this sort of thing," said Kobilka, standing in the dining room of his Palo Alto home and fielding calls from well wishers and media from around the globe. "I didn't know it was this big." ### For advertising and promotion on HealthNewsDigest.com please contact Mike McCurdy: tvmike13@HealthNewsDigest.com or 877-634-9180 HealthNewsDigest.com is syndicated worldwide, to thousands of journalists in all media, and health-related websites. www.HealthNewsDigest.com Top of Page 
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