Life on Earth obeys a rhythm that sets the rotation of the planet around itself and around the Sun. Most living organisms have internal “clocks” - mechanisms that allow them to live in accordance with this rhythm. Hall, Rosbash and Young looked into the cage and saw how the biological clock worked.
Drosophila flies served as model organisms. Geneticists have managed to identify a gene that controls the rhythm of life of insects. It turned out that it encodes a protein that accumulates in cells at night and is slowly utilized during the day. Later, several more proteins were discovered that are involved in the regulation of circadian rhythms. It is now clear to biologists that the mechanism regulating the daily routine is the same for all living organisms, from plants to humans. This mechanism controls activity, hormone levels, body temperature and metabolism, which vary depending on the time of day. Since the discoveries of Hall, Rosbash and Young, much data has emerged on how sudden or persistent deviations in lifestyle from a given “ biological clock» may be hazardous to health.
The first evidence that living creatures have a “sense of time” appeared back in the 18th century: then the French naturalist Jean Jacques d'Hortu de Mairan showed that mimosa continues to open its flowers in the morning and close in the evening, even being in the dark around the clock. Further research showed that not only plants sense the time of day. but also animals, including people. The periodic change in physiological indicators and behavior during the day was called circadian rhythms - from lat. circa- circle and dies- day.
In the 70s of the last century, Seymour Benzer and his student Ronald Konopka found a gene that controls circadian rhythms in Drosophila and defined its period. In 1984, Jeffrey Hall and Michael Rosbash, working at Brandelis University in Boston, and Michael Young at the Rockefeller University of New York, isolated the gene period, and then Hall and Rosbash figured out what the protein it encodes, PER, does—and it accumulates in the cell at night and is spent throughout the day, so you can judge the time of day by its concentration.
This system, as suggested by Hall and Rosbash, regulates itself: the PER protein blocks the activity of the period gene, so protein synthesis stops as soon as there is too much of it, and resumes as the protein is consumed. All that remained was to answer the question of how the protein gets into the cell nucleus - after all, only there it can influence the activity of the gene.
In 1994, Young discovered a second gene important for circadian rhythms, timeless, which encodes the TIM protein, which helps the PER protein cross the nuclear membrane and block the period gene. Another gene doubletime, turned out to be responsible for the DBT protein, which slows down the accumulation of the PER protein - so that the cycle of its synthesis and pauses between them lasts for 24 hours. In subsequent years, many other genes and proteins were discovered - parts of the subtle mechanism of the "biological clock", including those that allow you to "wind up the hands" - proteins whose activity depends on illumination.
Circadian rhythms regulate the most different aspects life of our body, including genetic level: Some genes are more active at night, some during the day. Thanks to the discoveries of the 2017 laureates, the biology of circadian rhythms has become a vast scientific discipline; dozens are written every year scientific works about how the “biological clock” works different types, including humans.
So, for those people who do science or talk and write about it, the most important week of the year has arrived. Traditionally, in the first week of October, the Nobel Committee announces the Nobel Prize laureates. And traditionally, we are the first to recognize the laureates of the prize in physiology or medicine (yes, for some reason in Russian this union has turned into “and”, but correctly - either one or the other).
In 2017, the Karolinska Institute, which awards these prizes, surprised everyone. It is no secret that many experts and agencies make prophecies and predictions about the laureates. This year, for the first time, the Clarivate Analytics agency, which separated from the Thomson Reyters agency, made predictions. In the field of medicine, they predicted victory for Lewis Cantlie for the discovery of a protein that is responsible for the development of cancer and diabetes, Karl Friston for neuroimaging techniques, and the spouses Yuan Chan and Patrick Moore for the discovery of the herpes virus that causes Kaposi's sarcoma.
However, unexpectedly for everyone, three Americans received the prize (which was not at all unexpected) for the discovery molecular mechanisms circadian rhythms - the internal molecular clock of humans, animals and plants. Yes, almost all living beings. The same thing that is called biorhythms.
What did Michael Young of the Rockefeller University in New York, Michael Rosbash of Brandeis University, and Jeffrey Hall of the University of Maine discover?
To begin with, let's say that they did NOT discover circadian rhythms (from the Latin circa - around and diem - day). The first hints of this appeared in ancient times (and it is not surprising, we are all awake during the day and asleep at night). The gene responsible for the operation of the internal clock was also not discovered by our heroes. This series of experiments was carried out on fruit flies by Seymour Benzer and Ronald Konopka. They were able to find mutant flies in which the duration of the circadian rhythms was not 24 hours, like those living in nature (or like people), but 19 or 29 hours, or no circadian rhythms were observed at all. It was they who discovered the period gene, which “rules” rhythms. But alas, Benzer died in 2007, Konopka in 2015, without waiting for his Nobel Prize. This often happens in science.
So, the period gene itself, or PER, encodes the PER protein, which conducts the orchestra of circadian rhythms. But how does he do this, and how is the cyclical nature of all processes achieved? Hall and Rosbash proposed a hypothesis according to which the PER protein enters the cell nucleus and blocks the work of its own gene (as we remember, genes are just instructions for protein assembly. One gene - one protein). But how does this happen? Jeffrey Hall and Michael Rosbash showed that the PER protein accumulates in the cell nucleus overnight and is used up during the day, but they did not understand how it managed to get there. And then the third laureate, Michael Young, came to the rescue. In 1994, he discovered another gene, timeless, which also encodes a protein - TIM. It was Young who showed that PER can enter the cell nucleus only by combining with the TIM protein.
So, let's summarize the first discovery: When the period gene is active, the so-called messenger RNA of the PER protein is produced in the nucleus, which, as a model, will produce protein in the ribosome. This messenger RNA exits the nucleus into the cytoplasm, becoming the template for the production of the PER protein. Then the loop closes: the PER protein accumulates in the cell nucleus when the activity of the period gene is blocked. Young went on to discover another gene, doubletime, which encodes the DBT protein, which can “tune” the accumulation of the PER protein, shifting it in time. It is thanks to this that we can adapt to changes in time zone and the length of day and night. But - if we change day to night very quickly, the squirrel cannot keep up with the jet, and jet lag occurs.
It should be noted that the 2017 award is the first award in 117 years that in some way relates to the sleep-wake cycle. In addition to the discovery of Benzer and Konopka, other researchers of circadian rhythms and sleep processes did not receive their awards, such as one of the founders of chronobiology Patricia DeCorsi, the discoverer of the “rapid” phase of sleep Eugene Azerinsky, one of the fathers of somnology Nathaniel Kleitman... So what can we call the current The decision of the Nobel Committee is significant for everyone who works in this area.
In 2017, the Nobel Prize in Medicine was awarded to three American scientists who discovered the molecular mechanisms responsible for the circadian rhythm - the human biological clock. These mechanisms regulate sleep and wakefulness, the functioning of the hormonal system, body temperature and other parameters human body, which change depending on the time of day. Read more about the scientists' discovery in the RT material.
Winners of the Nobel Prize in Physiology or Medicine Reuters Jonas Ekstromer
The Nobel Committee of the Karolinska Institutet in Stockholm on Monday, October 2, announced that Nobel Prize 2017 in the field of physiology and medicine awarded to American scientists Michael Young, Jeffrey Hall and Michael Rosbash for their discoveries of the molecular mechanisms that control the circadian rhythm.
“They were able to get inside the body’s biological clock and explain how it works,” the committee noted.
Circadian rhythms are cyclic fluctuations in various physiological and biochemical processes in the body associated with the change of day and night. Almost every organ of the human body contains cells that have an individual molecular clock mechanism, and therefore circadian rhythms represent a biological chronometer.
According to a release from the Karolinska Institutet, Young, Hall and Rosbash were able to isolate a gene in fruit flies that controls the release of a special protein depending on the time of day.
“Thus, scientists were able to identify the protein compounds that are involved in the operation of this mechanism and understand the work independent mechanics this phenomenon within each individual cell. We now know that the biological clock works on the same principle in the cells of other multicellular organisms, including people,” the committee that awarded the prize said in a release.
- Drosophila fly
- globallookpress.com
- imagebroker/Alfred Schauhuber
The presence of biological clocks in living organisms was established at the end of the last century. They are located in the so-called suprachiasmatic nucleus of the hypothalamus of the brain. The nucleus receives information about the level of light from receptors on the retina and sends a signal to other organs using nerve impulses and hormonal changes.
In addition, some nuclear cells, like the cells of other organs, have their own biological clock, the work of which is ensured by proteins whose activity changes depending on the time of day. The activity of these proteins determines the synthesis of other protein bonds, which generate circadian rhythms in the life of individual cells and entire organs. For example, being indoors with bright lighting at night can shift the circadian rhythm, activating protein synthesis PER genes, usually starting in the morning.
The liver also plays a significant role in circadian rhythms in mammals. For example, rodents like mice or rats are nocturnal animals and eat in the dark. But if food becomes available only during the day, their liver circadian cycle shifts by 12 hours.
Rhythm of life
Circadian rhythms are daily changes in the body's activity. They include the regulation of sleep and wakefulness, the release of hormones, body temperature and other parameters that change in accordance with the circadian rhythm, explains somnologist Alexander Melnikov. He noted that researchers have been developing in this direction for several decades.
“First of all, it should be noted that this discovery is not yesterday or today. These studies were carried out for many decades - from the 80s of the last century to the present - and made it possible to discover one of the deep mechanisms that regulate the nature of the human body and other living beings. The mechanism that scientists discovered is very important for influencing the body’s circadian rhythm,” said Melnikov.
- pixabay.com
According to the expert, these processes occur not only due to the change of day and night. Even in polar night conditions, circadian rhythms will continue to operate.
“These factors are very important, but very often they are impaired in people. These processes are regulated at the gene level, which was confirmed by the award winners. Nowadays, people change time zones very often and are exposed to various stresses associated with sudden changes circadian rhythm. Tense rhythm modern life can affect the correct regulation and opportunities for rest of the body,” concluded Melnikov. He is confident that the research of Young, Hall and Rosbash provides an opportunity to develop new mechanisms for influencing the rhythms of the human body.
History of the award
The founder of the prize, Alfred Nobel, in his will entrusted the selection of the laureate in physiology and medicine to the Karolinska Institute in Stockholm, founded in 1810 and one of the leading educational and scientific medical centers peace. The university's Nobel Committee consists of five permanent members, who, in turn, have the right to invite experts for consultation. There were 361 names on the list of nominees for this year's award.
The Nobel Prize in Medicine has been awarded 107 times to 211 scientists. Its first laureate was in 1901 German doctor Emil Adolf von Behring, who developed a method of immunization against diphtheria. The Karolinska Institute Committee considers the most significant prize to be the 1945 prize awarded to British scientists Fleming, Cheyne and Florey for the discovery of penicillin. Some awards have become irrelevant over time, such as the award awarded in 1949 for the development of the lobotomy method.
In 2017, the bonus amount was increased from 8 million to 9 million Swedish kronor (about $1.12 million).
The award ceremony will traditionally take place on December 10, the day of the death of Alfred Nobel. Prizes in the fields of physiology and medicine, physics, chemistry and literature will be awarded in Stockholm. The Peace Prize, according to Nobel's will, is awarded on the same day in Oslo.
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