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Nobel Laureate Chemistry 2015: Paul Modrich

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For Nobel Prize Winner Paul Modrich science is about using inner creativity and seeing an idea transform step by step into new exciting discoveries. A curiosity and love for problem-solving research that has given us groundbreaking knowledge about human DNA. The camera flashes were the only thing that was heard for the first minutes as Paul Modrich, together with the other Nobel Prize Laureates, entered the stage in front of the international press. Journalists and photographers had been invited to a press conference with the Nobel Prize winners in Chemistry, Physics and Economic Sciences at the Royal Academy of Sciences in Stockholm, starting off the festivities of the intensive Nobel week. Nowadays the Laureates are as equally sought-after as any rock star and the schedule is loaded with interviews, lectures and of course the award ceremony and subsequent Nobel Banquet. We got a few minutes after the press conference for some questions and a photo shoot with the now world-famous Howard Hughes Medical Institute Investigator and Duke Medical School Professor. When Modrich and his wife Vickers Burdett, also a Duke biochemist, got the life-changing call about the Nobel Prize at the beginning of October they were on vacation in New Hampshire. In shock, but still in the calm before the storm. Since then, “It has been nonstop,” Modrich says, as we sit down in one of the ornate halls. The media attention appears to a bit overwhelming for the 69-year-old biochemist, who has been described as somewhat modest. Being appointed as one of the winners of the Nobel Prize in Chemistry has been an overwhelming experience. “It has really changed our lives – in a good way,” he says. “It’s also gratifying to know that your colleagues appreciate your work. You can never know that. In science, it’s other people that determine the value of your work.” The mismatch repair system Modrich shares this year’s Nobel Prize in Chemistry for his studies on how mistakes in the DNA code are repaired. He started out investigating the question of DNA repair in the late 1970s and his key contribution has been to identify and characterize the proteins in the mismatch repair (MMR) system, showing how the system functions as a copyeditor to correct the rare errors left by DNA polymerase. His findings have given us invaluable knowledge to better understand what keeps our DNA intact. Also, as he concludes, looking back on his years of research, this has played an important role in comprehending the emergence of certain types of cancer. Modrich and his colleagues have shown that inactivation of the mismatch repair system is the cause of the most common form of hereditary colon cancer, and “This pathway also has indications for certain neurodegenerative diseases,” he says. The work of dissecting the molecular mechanisms of MMR in humans continues and Modrich is also exploring the role of MMR in how certain cancers become resistant to chemotherapy, as
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