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Tuesday, October 17, 2017

circadian rhythm

The 2017 Nobel Prize in Physiology or Medicine was awarded to Jeffrey Hall, Michael Rosbash, and Michael Young. Talha Burki reports.
The 2017 Nobel Prize in Physiology or Medicine has been jointly awarded to Jeffrey Hall, Michael Rosbash, and Michael Young for their work in uncovering the mechanism that underpins the circadian rhythm. In a statement announcing the award on Oct 2, the Nobel Assembly noted that the three winners “were able to peek inside our biological clock and elucidate its inner workings”. In doing so, the laureates have opened up a field of study with implications for many disorders and diseases.
“The problem of the circadian rhythm had puzzled people for a long time”, recalls Young. It was clearly some kind of internal system, since plants and animals kept in the dark continued to follow the same rhythm. “The question was: what was the clock made from? What was the quartz crystal that kept circadian time?” Rosbash told The Lancet. In the early 1980s, he and Hall were working at Brandeis University in Waltham, MA, USA. Rosbash remains there, and Hall has now retired. Meanwhile, Young was at Rockefeller University, New York City, NY, USA, where he still runs a laboratory.
“The real star of this story is the fruit fly”, said Rosbash. “Jeff had been working as a fruit fly geneticist since his graduate days—it was through my friendship with him that I got involved in all this.”

Seymour Benzer and Ronald Konopka had already shown that mutations in a specific gene in fruit flies either obliterated their inner clock or disrupted its speed. “It was a fascinating question: what could be sitting on those chromosomes that could be mutated to change the clock in such a significant fashion?” said Young. In 1984, the two laboratories delivered the same answer. They identified the period gene that controlled the circadian rhythm in fruit flies.

Hall and Rosbash went on to decipher the central mechanism. Period encodes a protein that builds up at night and degrades during the day—it follows a circadian rhythm, in other words. “We discovered that the production of the protein was turned off by the protein itself; it was a negative feedback loop”, said Rosbash. Young clarified how the loop functioned. “We found a gene that we called timeless”, he said. “Its protein product formed a complex with the period protein product, and when it did so, it moved to the nucleus and formed the negative regulation system that was originally hypothesised.”/.../

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