The American scientists Jeffrey C Hall, Michael Rosbash and Michael W Young, who have won this year’s prize. Illustration NobelPrize.org
The American scientists Jeffrey C Hall, Michael Rosbash and Michael W Young, who have won this year’s prize. Illustration NobelPrize.org

The Nobel Assembly at the Karolinska Institute announced today that Michael Rosbash, a Howard Hughes Medical Institute (HHMI) investigator at Brandeis University, Jeffrey C. Hall of Brandeis University and Michael W. Young of the Rockefeller University are the recipients of the 2017 Nobel Prize in Physiology or Medicine for their discoveries of molecular mechanisms controlling the circadian rhythm.

Microbes, plants, and animals all run on a 24-hour cycle, one that’s flexible enough to gradually reset itself, although it can take a few days after transcontinental travel. The biological systems responsible for maintaining this circadian clock require a lot of proteins that undergo complex interactions, and the new laureates are being honored for their use of genetics to start unraveling this complexity.

These researchers played an important role in identifying the ways the cells in organisms regulate the internal body clock. These are also known as the chronotype or circadian rhythm. This determines when people feel most awake or most sleepy.

This is a Nobel Prize-winning discovery because it shows how biology regulates these body clocks for living organisms ranging from fruit flies (which these researchers originally worked with) to humans.

“Some people still think the body clock is something esoteric rather than a profoundly biological function,” chronobiologist Till Roenneberg wrote in his book “Internal Time: Chronotypes, Social Jet Lag, and Why You’re So Tired,” in a section explaining some of Robash’s work with fruit flies.

This body clock influences biological functions such as hormone levels, sleep, body temperature and metabolism. Generally we call it as jetlag when our internal clock and external environment move out of sync when we change time zones.

It would take nearly 250 years to move from this observation to any sort of biological handle on the system. The change, as it has been so many times, was brought about using the fruit fly Drosophila. A genetic screen in the 1960s identified three different mutations that altered flies’ circadian clock: one that lengthened its 24-hour period, one that shortened it, and one that left it erratic. Mapping these revealed that all of them affected the same gene. From there, however, the field had to wait 20 years for us to develop the technology to clone the gene responsible for these changes, named period.

The noble team said that – 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 a protein components additionally of this machinery, exposing the mechanism governing the self-sustaining clockwise inside the cell. 

Hall and Rosbash discovered that this gene played a role in causing cells to produce what they named the “PER” protein, which accumulated throughout the night before breaking down during the day. They figured out that the period gene would cause the PER protein to build up until it hit a high enough accumulation that it switched off the period gene. Once protein levels degraded enough, the gene would switch back on, coding for more protein production.

Any biological creature will not have high energy all the day. There is a need to be on high alert and able to react quickly. At other time there must be other activities such as eat, rest, and sleep to regain energy. Our body clock regulates these phases, which is why most of us sleep at night and are awake during the day – though there’s significant variation between individuals as to when we feel most awake and most asleep, regulated by genetics and other factors.

While this is pretty clearly a win for the physiology side of the “Physiology or Medicine,” the Nobel Foundation’s literature mentions that a number of human disorders involve dysfunction of our circadian rhythms. And when these go wrong, they alter many basic body functions, like regulation of metabolism, hormone levels, and memory consolidation. Sleep problems are also typical hallmarks of depression and bipolar disorders. So, while the three laureates probably weren’t thinking medicine when they started messing up fruit flies, their work may ultimately have some medical impact.

It is a matter of preference and an issue of biology and one that could explain why on a certain schedule you thrive and on another schedule, everything feels wrong.

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