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Michael Rosbash takes a phone call at his home, Monday, Oct. 2, 2017, in Newton, Mass. Rosbach is one of the Americans awarded this year’s Nobel Prize in physiology or medicine for discovering the molecular mechanisms that control humans’ circadian rhythm. Photo: Bill Sikes, AP

Decades of discoveries into the natural working of circadian rhythms earned three American researchers this year’s Nobel Prize in Physiology or Medicine, the Swedish judges announced today.

Jeffrey C. Hall, Michael Rosbash, and Michael W. Young were jointly awarded this year’s prize for their work, which started in the 1980s with their discovery of how a single fruit fly gene is translated into the insect’s molecular workings.

Their “seminal” work has essentially changed the way science looks at biology, said the Nobel Assembly at Karolinska Institutet in a statement.

“The paradigm-shifting discoveries by the laureates established key mechanistic principles for the biological clock,” they said.

The three published a series of investigations into the genetic and chemical workings of Drosophila in the 1980s and 1990s, providing crucial answers to the questions raised by other scientists.

Two scientists in particular had paved the way for the work of today’s Nobel trio. Seymour Benzer and Ronald Konopka discovered the gene “period” in a laboratory at the California Institute of Technology in the mid-1970s. Konopka had isolated the gene using ethyl methanesulfonate to induce point mutations. Benzer and Konopka would eventually co-author other papers on the circadian investigation with the Nobel laureates in the 1980s and 1990s. (Benzer died in 2007, and Konopka in 2015.)

But that initial work was just identifying the “molecular clock.” The three Nobel laureates announced today actually showed how it worked.

In the 1980s, Hall and Rosbash were colleagues at Brandeis University, while Young worked independently at Rockefeller University. (Rosbash talked about the beginning of his work with Hall, who had been a postdoctoral student in Benzer’s laboratory, in a 2015 video. Among their interests were alcohol and tobacco – and a daily basketball game played at precisely 12 noon).

In 1984, both groups of scientists published a groundbreaking finding: the link from the “period” gene to the PER protein. That protein regulated itself in a feedback loop in the nucleus of fruit fly cells that established a 24-hour cycle of behavior from day to night, they found. Hall and Rosbash (along with Konopka) published in the journal Cell, showing how the PER protein builds up in the nucleus at night, while Young and others published their similar findings in Nature.

Young made the next breakthroughs: first with a second gene called “timeless” which encoded another protein called TIM which effectively assisted the inhibitory feedback. Then in 1998 Young identified the “doubletime” gene and its protein translation called DBT, which itself regulated the buildup of the PER protein.

Since their work established the expanding tapestry of the genetic-proteomic circadian clock, science has looked at its implications in a variety of fields. For instance, disruptions in the internal clock are suspected in the presentation of depression, mental illness, and even addiction. Some scientists have even started looking into the chemical workings of the brain to determine whether circadian rhythms are regular enough to determine time of death in homicide investigations, as reported in Forensic Magazine.

Colleen McClung, an associate professor of psychiatry at the University of Pittsburgh, told Laboratory Equipment the discoveries of Hall, Rosbash, and Young opened up the field for important research - including her own.

"We could not do any of the translational work that we do today without the pioneering work of these Nobel Prize winners," McClung said. "We are now using our knowledge of circadian rhythms to develop new therapies that stabilize circadian rhythms, or take advantage of the difference in how tumors and other cells are regulated during the day versus the night."

David Eisner, the president of the United Kingdom’s Physiological Society, issued a statement of congratulations to the foundational work of Hall, Rosbash, and Young.

“Their research has transformed our understanding of circadian biology,” Eisner said. “Understanding how our daily biological clock workers and how our body adapts to different phases of the day has huge implication for our health and well-being.”

The Nobel Prize announcements continue for another week. The Physics Prize will be announced on Tuesday, the Chemistry Prize on Wednesday, the Literature Prize on Thursday, the Peace Prize on Friday, and the Economics Prize next Monday.

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