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The Nobel Assembly at Karolinska Institutet announced today that it had awarded the 2017 Nobel Prize Physiology or Medicine jointly to Jeffrey C. Hall, Michael Rosbach and Michael W. Young “for their discoveries of molecular mechanisms controlling the circadian rhythm.” (You can watch Professor Thomas Perlmann, Secretary of the Nobel Committee for Physiology or Medicine, announce the 2017 Nobel Prize in Physiology or Medicine in a video on the homepage of the Nobel Prize’s website nobelprize.org.) Living organisms, including humans, are governed by an “internal, biological clock that helps them anticipate and adapt to the regular rhythm of the day.” Figuring out how that clock works has been the challenge. Through their work, the three Nobel laureates have been able to “explain how plants, animals, and humans adapt their biological rhythm so that it is synchronized with the Earth’s revolutions.” The term circadian comes from the Latin word circa meaning “around” and dies meaning “day”.
In experiments using fruit flies, the Nobel laureates “isolated a gene that controls the normal daily biological rhythm.” As the press release explains, “They showed that this gene encodes a protein that accumulates in the cell during the night, and is then degraded during the day. Subsequently, they identified additional protein components of this machinery, exposing the mechanism governing the self-sustaining clockwork inside the cell. We now recognize that biological clocks function by the same principles in cells of other multicellular organisms, including humans.”
Investigations into the science of the diurnal cycle has been the subject of extensive study. In the 18th century the astronomer Jean Jacques d’Ortous de Mairan examined the behavior of mimosa plants after he noticed that their leaves “opened towards the sun during daytime and closed at dusk.” Wondering, “What would happen if the plant was placed in constant darkness” he observed, “that independent of daily sunlight the leaves continued to follow their normal daily oscillation.”
In the 1970s, Seymour Benzer and Ronald Konopka looked into whether or not it was possible to “identify genes that control the circadian rhythm in fruit flies.” They were able to demonstrate “that mutations in an unknown gene disrupted the circadian clock of flies. They named this gene period.”
This year’s Nobel Prize recipients focused on “how the clock actually works.” In 1984, the trio was successfully able to isolate the gene called period. Jeffrey C. Hall and Michael Rosbach, worked together “in close collaboration” at Brandeis University in Waltham, Mass., a suburb of Boston, while Michael W. Young was at Rockefeller University in New York. Hall and Rosbach continued their research and were able “to discover that PER, the protein encoded by period, accumulated during the night and was degraded during the day. Thus, PER protein levels oscillate over a 24-hour cycle, in synchrony with the circadian rhythm.” The next step was to figure out how the “circadian oscillations could be generated and sustained.”
In 1994, Young discovered a second clock gene, called timeless. His studies “showed that when TIM bound to PER, the two proteins were able to enter the cell nucleus where they blocked period gene activity to close the inhibitory feedback loop.” (Fig. 2B) Discovery of a “feedback mechanism” explained how the “oscillation of cellular protein levels emerged” but there were still questions, such as “what controlled the frequency of the oscillations?” Young in turn found another gene, doubletime, that was able to “encode the DBT protein that delayed the accumulation of the PER protein.
The trio’s work in discovering the “key mechanistic principles for the biological clock” are “paradigm-shifting.” The three men have gone on to identify “other molecular components of the clockwork mechanism” including additional proteins that are needed to activate the period gene, and “the mechanism by which light can synchronize the clock.”
Listen to/read a telephone interview with Michael Rosbash following the announcement of the 2017 Nobel Prize in Physiology or Medicine.
Read a telephone interview with Michael W. Young following the announcement of the 2017 Nobel Prize in Physiology or Medicine.
The Nobel Assembly, comprised of 50 professors at the Karolinska Institutet, awards the Nobel Prize in Physiology or Medicine. The prize has been given since 1901 “to scientist who have made the most important discoveries for the benefit of mankind.”
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