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Nobel Prize in medicine for deciphering the mechanism of biological clocks

Jeffrey C. Hall, Michael Rosbash and Michael W. Young have been awarded the Nobel Prize in Medicine for unraveling the molecular mechanisms that control the circadian rhythm, ie the biological oscillations that regulate hormone levels, sleep, body temperature and metabolism. His misfit is responsible for disorders like jet lag. Living organisms, including humans, have an internal biological clock that helps them anticipate and adapt to the regular rhythm of the day. Jeffrey C. Hall, Michael Rosbash and Michael W. Young have been working for years to decipher their inner workings. His discoveries, which have earned him the Nobel Prize in Medicine and Physiology today, explain how plants, animals and humans adapt their biological rhythm to be synchronized with the rotation of the Earth.

Using fruit flies as a model organism, Hall (1945, New York), Rosbash (1944, Kansas) and Young (1949, Miami) isolated a gene that controls the normal daily biological rhythm.

The three experts from US institutions, Hall, a professor at the University of Maine, Rosbash, at Brandeis University and Young researcher at Rockefeller University, showed how this gene encodes a protein that accumulates in the cell overnight , and then degrades during the day.

Later, they identified more protein components of this machinery and gave with the mechanism that controls said internal clock of the cell. It is now known that these biological clocks function in the same way in other multicellular organisms, including humans. The circadian rhythm is responsible for regulating behavior, hormone levels, sleep, body temperature and metabolism. And, in the same way, his misfit is responsible for several disorders, such as the known jet lag.

The next step was to understand how these circadian oscillations could be generated and maintained. Hall and Rosbash hypothesized that PER protein blocked the activity of the described gene.

The experts proposed that, by means of a feedback inhibitory circuit, the PER protein could prevent its own synthesis and, therefore, regulate its level in a continuous cyclic rhythm.

However, some pieces of the puzzle were still missing. Hall and Rosbash had shown that PER protein accumulated in the nucleus overnight, but it remained to be seen how it got there.

In 1994, Young discovered a second gene from this biological clock, which encodes the TIM protein, needed for a normal circadian rhythm. Thus, it showed that when TIM binds to PER, the two proteins are able to enter the nucleus of the cell where they block gene activity, closing the inhibitory feedback loop.

The findings of the three laureates established key mechanical principles of the biological clock. Moreover, during the following years other molecular components of the clock mechanism were clarified, which explained its stability and function.

For example, additional proteins required for gene activation were identified, as well as for the mechanism by which light can synchronize the clock.

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