Three scientists, Jeffrey C. Hall, Michael Rosbash and Michael W. Young have been awarded the most reputed Nobel Prize 2017, in physiology or medicine on Monday. The US biology trio’s discoveries “explain how plants, animals and humans adapt their biological rhythm so that it is synchronized with the Earth’s revolutions,” according to the Nobel Assembly. Hall, 72, Rosbash, 73, and Young, 68,“were able to peek inside our biological clock and elucidate its inner workings,” it said. Scientists and doctors now know these day-and-night cycles keep creatures alive by regulating our alertness, sleep patterns, blood pressure, hormones, body temperature and when we eat.
Scientists had known about circadian rhythms since 1729, when astronomer Jean Jacques d’Ortous de Mairan placed a mimosa plant into a dark room and noticed that the plant’s leaves still opened and closed at the same times every day. Through a series of breakthroughs, Hall, Rosbash and Young showed these internal clocks are self-regulated. In the morning, sunlight switches on the “period” gene, which begins to produce its protein. This protein accumulates in the cytoplasm, the chunky space in our cells that surrounds the nucleus where our DNA and the period gene are housed.
Hall and Rosbash found that period proteins built up throughout the day until nightfall, when their levels began to gradually drop. When dawn broke, period proteins disappeared, and the cycle repeated itself. They hypothesized that the period protein was somehow crossing into the nucleus to shut off its own gene, in what they dubbed a transcription-translation feedback loop.
When the period gene is active, period (PER) messenger RNA is made. This messenger RNA is transported to the cell’s cytoplasm and serves as template for the production of PER protein. The PER protein accumulates in the cell’s nucleus, where the period gene activity is blocked. This gives rise to the inhibitory feedback mechanism that underlies a circadian rhythm. Illustration by the Nobel Assembly at the Karolinska Institutet
Young extended the work by uncovering two additional protein, named “timeless,” which was responsible to escorting the period protein into the nucleus. Young’s lab also identified a third protein — called doubletime — that controlled the timing of the destruction of the period proteins
In humans, these clock genes control the production of insulin and other hormones involved in maintaining how our bodies process food. Disruption of the genes through sleep deprivation or mutation alters brain functions and has been tied to sleep disorders, depression, bipolar disorder and memory defects. Out of whack circadian rhythms also increase a person’s risk for cancer, obesity, diabetes and other metabolic disorders.