Earning the Nobel Prize: A Trio’s Molecular Sketch of the Body Clock

By: Renald James Legaspi (Polintons)
(Left to right) Jeffrey C. Hall, Michael Rosbash and Michael W. Young, the American scientists who were awarded the 2017 Nobel Prize for Physiology or Medicine for their discoveries on the molecular mechanism of our biological clock. Image taken from: Nobelprize.org

"People used to think that biological clocks were not only mysterious, they were seen almost as miracles. This is no longer the case”- Jeffrey Hall, 2017 Nobel laureate for Physiology or Medicine

Every day, most of us start our lives early, probably as early as six in the morning. Some even wake up before the sun rises. We are so used to this routine that even in weekends wherein we anticipate to get few doses of extra sleep, our own body clock fails us. And in the night, even with the presence of the heavy workload that force us to stay awake, our eyes discreetly close before the lamp of our desk. These get us to conclusion that our physical bodies follow a well-coordinated regular pattern, commonly known as circadian rhythm. But how does this “body clock” actually work?

This was answered by a trio of American scientists who, in 2017, bagged the Nobel Prize in Physiology or Medicine for their elucidation of the molecular basis for the circadian rhythm of fruit flies. 

These men in the names of Jeffrey Hall, Michael Rosbash and Michael Young took their prize money totaling $367,000 during the Nobel Assembly at the Karolinska Institute in Stockholm for their discovery which revealed the very intricate molecular basis of our body clock.

Biological clock plays an important role in many facets of our physiology that its mechanism has been a vital discourse and at the same time, a lingering mystery among scientists throughout history. Notably, during 1970s, Seymour Benzer, a behavioral geneticist, with his student Ronald Konopka experimented on fruit flies to possibly identify the genes controlling the circadian rhythm. During their work, they discovered the period gene, which is located in the X chromosome of Drosophila, by inducing mutations on previously unknown gene and looking in the disruptive effects of mutagenesis on circadian rhythm.

Later, in 1984, Hall and Rosbash working at Brandeis University, and Young at Rockefeller University, first isolated and sequenced the period gene to which the discovery of its product, PER protein, a protein that accumulates during the night and is “degraded” during the day. At this point, the body clock "puzzle" is slowly forming a complete picture.

With this discovery, it is now their job to relate this to the sustenance and generation of circadian oscillations. They hypothesized that inhibitory feedback loop is present wherein the PER protein inhibits its own synthesis by blocking the activity of the period gene.

A perplexity, however, concerning some details of the model arise from the question of how the PER protein,produced in the cytoplasm, could actually be able to block the activity of the per gene in the DNA which safely lodged inside the nucleus.

In 1994, Young brings the second clock gene, timeless, in the picture. Timeless codes for TIM protein which binds to PER protein enabling the entry of the two molecules into the nucleus wherein the inhibition of per gene happen. Overall, these explain the oscillations in circadian rhythm; however, there is the requirement to understand what controls the frequency of these oscillations. 

Yet again, Michael Young discovered another gene, doubletime, which produces DBT protein. This protein delays the accumulation of the PER protein. This discovery finally provided the last missing traces of a good sketch of the molecular mechanism of our biological clock.

By providing the answers to the most elusive questions concerning our biological clock, these scientists, in no doubt, deserve the Nobel Prize. As James Rothman said, “It is fabulous to see the foundational discoveries of this trio recognized in this richly deserved and long overdue Nobel Prize.”

References:
Kolata, G. (2017, October 2). 2017 Nobel Prize in Medicine Goes to 3 Americans for Body Clock Studies. Retrieved from The New York Times: https://www.nytimes.com/2017/10/02/health/nobel-prize-medicine.html

Nobelprize.org. (2017, October 2). The Nobel Prize in Physiology or Medicine 2017. Retrieved from Nobelprize.org: https://www.nobelprize.org/nobel_prizes/medicine/laureates/2017/press.html


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