The 2017 Nobel Prize in Physiology or Medicine Announced

2017/10/02, the 2017 Nobel Prize in Physiology or Medicine jointly to Jeffrey C. Hall, Michael Rosbash and Michael W. Young for their discoveries of molecular mechanisms controlling the circadian rhythm. They will share 9 million Swedish kroner bonuses award.

2017 Nobel Prize in Physiology or Medicine

Jeffrey C. Hall, born in New York in 1945. 1971 received a Ph.D. from the University of Washington, 1971 to 1973 got post-doctoral position at the California Institute of Technology. In 1974 he joined the University of Brandeis. In 2002, he joined the University of Maine.

 

Michael Rosbash, born in 1944 in Kansas City, USA. 1970 received a Ph.D. from MIT, and post-doctoral at the University of Edinburgh in Scotland in following three years. Since 1974, he has been working at the University of Brandeis.

 

Michael W. Young, born in Miami, USA in 1949. He received his Ph.D. from the University of Texas in 1975. From 1975 to 1977, he was at Stanford University doing post-doctoral study. Since 1978, he has been working at the University of Rockefeller.

 

The life on earth has long been adapted to the rotation of the planet. For many years, we have known that there is a biological clock in a variety of living bodies, including humans, which can help us predict and adapt to the law of the cycle every day. But how does this clock actually work? Jeffrey C. Hall, Michael Rosbash and Michael W. Young explored the biological clock and successfully explained its internal operating mechanism. Their findings explain how plants, animals and humans are adapted to their biological rhythms and keep pace with the rotation of the earth.

 

This year’s winners use Drosophila as a model organism to isolate a gene that controls daily rhythms. They have shown that a protein encoded by this gene will accumulate at night and then decompose during the day. In addition, they also found that other biological components of this biological process, thus revealing the mechanism of cell management to maintain self-sustaining operation. Now we already know that the biological clocks of other multicellular living organisms, including humans, have the same operating mechanism.

 

With the extraordinary sophistication, the clock keeps our bodies adapting to the changes of every day: it regulates the body’s important functions such as behavior, hormonal levels, sleep, body temperature, and metabolism. When the external environment and the biological clock conflict in a short period, our health will be affected, such as when we fly across multiple time zones, there will be this situation. In addition, if the lifestyle and biological clock required rhythm have chronic incongruity, there will be various diseases appeared in the body.

 

Our Inner Clock

 

Most living organisms can predict and adapt to the daily changes in the environment. As early as the 18th century, the astronomer Jean Jacques d’Ortous de Mairan studied the mimosa, he found that mimosa leaves will open in the sun during the day and then close at dusk. He is curious that if mimosa continues to be in a dark environment, what changes will occur. And then he finds that, despite the absence of sunlight, the mimosa leaves keep their regular changes every day (Fig 1). Plants seem to have their own biological clocks.

Plant biological clock

Fig1. Plant biological clock

 

Later, other scientists found that not only plants, but animals and humans also have biological clocks to help their physiological state to adapt to the daily changes in the environment. This conventional fit is called the “circadian rhythm”, where the word “circadian” comes from “circa” (means “about”) and “dies” (means “one day”) in Latin. However, the mechanism of body biological clock is still unsolved mystery.

 

Identification of a Clock Gene

 

In the 1970s, American molecular biologist Seymour Benzer and his student Ronald Konopka suggested that whether there is a gene that controls its circadian rhythm in the fruit fly? After research, they found that mutations in an unknown gene in Drosophila did disrupt its circadian rhythm. They named the mutated gene “cycle” gene. However, there is a new problem: how does the periodic gene affect the circadian rhythm of Drosophila?

 

This year’s Nobel Prize winners, the object of the study is the fruit fly, too. They aimed at the research area of biological clock mechanism. In 1984, Jeffrey Hall and Michael Rosbash, these two scientists at the University of Brandeis in Boston, and Michael Young of the Rockefeller University, succeeded in separating the cycle genes. Jeffrey Hall and Michael Rossbash then found that the protein encoded by the cyclin was PER, which would accumulate at night and then decompose during the day. Thus, change period of PER protein levels were 24 hours, just simultaneous with circadian rhythm.

 

A Self-regulating Clockwork Mechanism

 

The key to the next step is to figure out how such rhythm changes are generated and maintained. Jeffrey Hall and Michael Rosbash conjecture that PER protein blocks the activity of the periodic gene. They further speculate that by suppressing the feedback loop, the PER protein may prevent its own synthesis and thus continuously and periodically adjust its level.

feedback-regulation-circadian

Fig2. Period gene feedback regulation

 

This model is “tempting”, but some fragments are missing. In order to block the activity of the periodic gene, the PER protein needs to contact with the nucleus. Jeffrey Hall and Michael Rosbash have confirmed that the PER protein is clustered in the nucleus at night, but the problem is how? In 1994, Michael Young discovered the second clock gene, timeless, which encodes the TIM protein required for circadian rhythms. He confirmed that when the TIM protein bound to the PER protein, the two proteins can both enter the nucleus, then block the cycle of gene activity, close the blocking feedback loop.

molecular components of the circadian clock

Fig3. Molecular components of the circadian clock.

 

This regulatory feedback mechanism explains how changes occur in protein levels. But there is still a question need to solve, what controls the frequency of this change? Michael Young identified another gene, doubletime, which encodes DBT protein that delays the aggregation of PER proteins. This explains how this circadian rhythm regulation is more appropriate for a 24-hour cycle.

 

The discovery of the three Nobel laureates’ are subversion of the traditional. These established the key mechanism of the biological clock. Later years, the other molecular components of the circadian rhythm mechanism were elucidated subsequently, further explained its stability and function. For example, this year’s winner also identified some additional proteins, which are necessary to activate the cycle of genes, and, in addition, to the light synchronization circadian rhythm.

 

Keeping On Time for Human Physiology

 

Many aspects of human physiology involve biological clocks. We know that all multicellular organisms, including humans, use a similar mechanism to control circadian rhythms. A large part of our genes are regulated by the biological clock, so that a carefully calibrated circadian rhythm adjusts our physiology to suit the different stages of the day. Since this major discovery, rhythmic biology has evolved into a broad and dynamic field of study that affects our health and well-being.

 

Jolin Gilles, Nobel Prize Selection Committee members, said that there are often appear long day or night in Nordic, the research results of this year’s winners reminded people who lived here to pay attention to keep the law of life and rest. She said: “Although the sun is still high, you also need sleep on time.”