00:00The Nobel Prize. The Nobel Prize in Physiology or Medicine 2017 was awarded jointly to Jeffrey C. Hall, Michael Rosbash and Michael W. Young for their discoveries of molecular mechanisms controlling the
00:29circadian rhythm. Jeffrey C. Hall, Michael Rosbash and Michael W. Young were able to peek inside our biological clock and elucidate its inner workings. Their discoveries explain how plants, animals and humans adapt their biological rhythm so that it is synchronized with the Earth's revolutions.
00:51Using fruit flies as a model organism, laureates isolated a gene that controls the normal daily biological rhythm. 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 additional protein components of this machinery, exposing the mechanism governing the self-sustaining clockwork inside the cell.
01:19We now recognize that biological clocks function by the same principles in cells of other multicellular organisms, including humans.
01:30With exquisite precision, our inner clock adapts our physiology to the dramatically different phases of the day. The clock regulates critical functions such as behavior, hormone levels, sleep, body temperature and metabolism.
01:46Our well-being is affected when there is a temporary mismatch between our external environment and this internal biological clock. For example, when we travel across several time zones and experience jet lag.
02:00There are also indications that chronic misalignment between our lifestyle and the rhythm dictated by our inner timekeeper is associated with increased risk for various diseases.
02:12Most living organisms anticipate and adapt to daily changes in the environment. During the 18th century, the astronomer Jean-Jacques d'Orthouse de Moraine studied Mimosa plants and found that the leaves opened towards the sun during daytime and closed at dusk.
02:30He wondered what would happen if the plant was placed in constant darkness. He found that independent of daily sunlight, the leaves continued to follow their normal daily oscillation.
02:44Plants seem to have their own biological clock.
02:47In 1984, Jeffrey Hall and Michael Rosbash, working in close collaboration at Brandeis University in Boston, and Michael Young and Rockefeller University in New York, succeeded in isolating the period gene.
03:02Jeffrey Hall and Michael Rosbash then went on to discover that PER, the protein encoded by period, accumulated during the night and was degraded during the day.
03:15Thus, PER protein levels oscillate over a 24-hour cycle, in synchrony with the circadian rhythm.
03:23The next key goal was to understand how such circadian oscillations could be generated and sustained.
03:31Jeffrey Hall and Michael Rosbash hypothesized that the PER protein blocked the activity of the period gene.
03:39They reasoned that by an inhibitory feedback loop, PER protein could prevent its own synthesis and thereby regulate its own level in a continuous cyclic rhythm.
03:51Jeffrey Hall and Michael Rosbash had shown that PER protein builds up in the nucleus during night.
03:58But how did it get there?
04:00In 1994, Michael Young discovered a second clock gene, timeless, encoding the TIM protein that was required for a normal circadian rhythm.
04:12In elegant work, he showed that when TIM bound to PER, the two proteins were able to enter the cell.
04:20Nucleus, where they blocked period gene activity to close the inhibitory feedback loop.
04:27The biological clock is involved in many aspects of our complex physiology.
04:32We now know that all multicellular organisms, including humans, utilize a similar mechanism to control circadian rhythms.
04:42And that's the same newsletters.
04:43At this point, we have the same flexibility for you to understand the values of a normal circadian rhythm.
04:47This is a link that we're gonna recognize, in terms of critically-related memories.
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