Nobel Prize 2017: What Makes Our Cells Tick?

Since Wednesday the Nobel Week in Stockholm is taking place. During one week the Laureates give press conferences and hold their Nobel Lectures. The week culminated in the Nobel Prize Award Ceremony and Banquet yesterday night, December 10. (see the full programme here)

source

In October this year, the Nobel Prize of physiology or medicine was awarded to the three chronobiologists Jeffrey Hall, Michael Rosbash and Michael Young. They received the prize for their discovery of the molecular machinery that controls the biological clock.

1 million euros for telling time

In 1984, Jeffrey Hall and Michael Rosbash in Boston, simultaneously with Michael Young in New York, discovered that they could disrupt the biological clock in fruit flies by mutating a gene. This gene, called period, encodes the protein PER, which happens in a 24-hour (circadian) rhythm. During the night, PER accumulates in cells and during the day it is degraded. They hypothesized that PER could control its own concentrations via an inhibitory feedback loop. However, PER was unable to enter the nucleus... How could it influence its own production? A few years later, Michael Young was able to answer this question. In 1994, he discovered another gene called timeless and its protein TIM which, when coupled with PER, enables both of them to cross the nuclear membrane. Now the only remaining question was how PER achieved its 24-hour rhythm. Michael Young also answered this question with the discovery of a third gene called doubletime. Doubletime encodes the protein DBT that can slow down the accumulation of PER and thus produces circadian oscillations.

Wide Implications
These mechanisms were later shown to be similar in humans. Yet, the importance of the biological clock is still underestimated today, not only by the general public, but also in medicine. From hormone concentrations, functioning of the immune system, to even behavior, the biological clock regulates a vast variety of physiological and psychological functions. Sleep is just one of the things under strong influence of the biological clock. In spite of the importance of sleep, millions of people work nightshifts, thereby desynchronizing their biological clock and jeopardizing their health. This year’s Nobel Prize might provide a leg up for the chronobiologists in their efforts to show the general public how important our internal clock is. It is a win, not only for the three scientists, but for the entire research field.

Zehring, W.A., Wheeler, D.A., Reddy, P., Konopka, R.J., Kyriacou, C.P., Rosbash, M., and Hall, J.C. (1984). P-element transformation with period locus DNA restores rhythmicity to mutant, arrhythmic Drosophila melanogaster. Cell 39, 369–376.

Bargiello, T.A., Jackson, F.R., and Young, M.W. (1984). Restoration of circadian behavioural rhythms by gene transfer in Drosophila. Nature 312, 752–754.


by Jan de Zeeuw, PhD Student AG Kunz