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)

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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

The Nobel Laureate Meetings at Lindau - Conference Report

The 67th Lindau Nobel Laureate Meeting ends today, this year it was dedicated to chemistry. Each year, a truly unique conference is held in Lindau, a small tranquil island located on Lake Konstanz in Germany, where students and over 20 Nobel Laureates get together to discuss and exchange ideas about science and society. One of our students attended the Meeting in 2011.

A history with future
Initiated by the two physicians Gustav Parade and Franz Karl Hein from Lindau, the Nobel Laureate Meetings were set up as an attempt to free Germany from its isolation to the global scientific community after the 2nd World War and as a gesture of reconciliation to those Nobel Laureates who had fled from Germany during the war. They convinced Count Lennart Bernadotte of Wisborg, a descendant of the royal Swedish family and associate of the Nobel Prize Committee in Stockholm, to assume patronage of the scientific meeting. With his support, they managed to raise sufficient public interest and funds to host the first meeting in 1951. Renowned personalities such as Otto Hahn, Otto Warburg, Max Born, Paul Dirac and Werner Heisenberg were among the first Nobel Laureates to come to Lindau. The discussions held at Lindau were not only of scientific nature but also carried important political messages. Drafted by Otto Hahn and Max Born in Lindau and signed by over 50 Nobel Laureates world-wide, the Mainau Declaration was published in 1955 as the first uniform appeal from scientists against the use of nuclear weapons.
In 1954, for the first time, the founders decided to invite selected students to the meeting, providing them a unique opportunity to get taught and inspired by those whose groundbreaking discoveries had shaped the world of science and medicine. Over the years, the close interaction between students and Nobel Laureates has become the very core of the Lindau meetings.
As the meetings grew, they became more and more interdisciplinary, inviting students and Laureates in the fields of medicine, physics, chemistry as well as economics. Each year in turn, the Lindau meetings are devoted specifically to one of these disciplines.

Reflecting on Lindau 2011
This year, I was among the fortunate students who got invited to the 61st Lindau Nobel Laureate Meeting in Physiology or Medicine, which was held from June 24th - July 1st. As a student of medicine and biomedical science, I was thrilled by the opportunity that lay in front of me but I was uncertain about my expectations from this conference. There is the fact that you are surrounded by 560 students from over 70 countries who are considered to be the best in their field of research, let alone 23 Nobel Laureates who have pretty much defined the way medicine has developed over the past decades.

Countess Bernadotte, Nobel Laureates and young Researchers

© Lindau Nobel Laureate Meetings Council

 

I had imagined that such a crowd could potentially create a very competitive atmosphere that puts pressure on the students to show themselves worthwhile. But the following days would prove me somewhat wrong, when my mindset completely changed to 'relax and get inspired'.
The conference days start with Nobel lectures in the morning, followed by group discussions in the afternoon, where the magic happens, where students can meet individual Laureates outside the purview of the media, organizers and chaperones and ask them anything that comes to their minds. Various discussion panels on global health issues (i.e. sustainable health care, infectious diseases, population growth etc.) were held in between, inviting prominent guests such as Bill Gates (representing the Bill and Melinda Gates Foundation), Unni Karunakara (president of Doctors without Borders) and Hans Rosling (GapMinder Foundation) to name a few. This was complemented by an exciting social program that provided plenty of opportunity to mingle with students from different countries and research areas and, of course, to bask in the glow of the Laureates' wisdom and knowledge. As naïve as this may sound, I was holding some hope that the magnitude of the Laureates' contributions, their work ethic and their recognized genius would rub off on me in these early stages of my professional scientific life. Above all, I wanted to pick the Laureates' brains about 'how' they approach and go about doing science. I soon realized that getting a uniform answer to my questions from the Laureates was a hopeless endeavor. But as much as their personalities and views about scientific practice differ, all Laureates shared a tremendous passion for science and retained an almost childish curiosity even at their respected ages. Most of them were very modest about receiving the Nobel Prize (and numerous other awards). As Sir Martin Evans (Medicine or Physiology 2007) pointed out during his talk: "The true award lies in finding the answer to the questions that fascinate you. Science awards are mere epiphenomena that might pop up along the way."

'Science awards are mere epiphenomena that might pop up along the way.' 

- Sir Martin Evans -

The invaluable discussions with the Laureates and students further shaped my understanding of what it means to be a scientist, what my place in society can be, and how it feels to be part of a global community of researchers sharing a passion for science. Moreover, I have now become a part of the history of the meetings myself, and it is this shared narrative that I will now retell to my peers and to future students. For pictures, videos and information on how you can attend the meetings visit http://www.lindau-nobel.org/ and http://lindau.nature.com/.

By Ha Thi Hoang, Alumni MD-MSc Student in Medical Neurosciences

this article originally appeared September 2011 in Volume 4 Issue 3, CNS Stimulation