The Nobel Prize in Physiology and Medicine for 2017 was awarded to American professors Jeffrey Hall, Michael Rosbashi and Michael Yangu. They studied the mechanism regulating the circadian rhythms of the body, the so-called cell clock. Representing the laureates, the expert of the Nobel Committee emphasized that this problem itself was far from Nova. Back in the XVIII century, one French scientist drew attention to some flowers that are revealed in the morning and closed overnight. The biologist put the experiment, placing flowers in full darkness for several days. And they behaved as if they were in vivo. A similar picture was observed when studying other plants and animals. Then the hypothesis about the internal watches of living organisms was first put forward. What are their essence?
Each of us knows what ordinary hours, we measure time using a pendulum. But it turns out that almost all of the living has its own internal clock, and instead of a pendulum in us "works" a change of day and nights, which are the result of the turn of the Earth around their axis, said Professor of the Skolkovsky Institute of Science and Technology, Professor at the University of Ratger University, Head of laboratories at the Institute of Molecular Genetics of the Russian Academy of Sciences and the Institute of Biology of the Geng of the Russian Academy of Sciences Konstantin Severinov. - From the very beginning of the appearance of life, all the living should have adapted to such a shift. Include these small hours in every cell of any body. And live on them. In accordance with their "testimony" to change its physiology - to run, sleep, eat and so on.
The current laureates in the late 70s decided to look inside these hours and understand how they work. For this, they studied the flies of Drozophil, were taken by insects with mutations, whose sleep and wake cycles were changed. Let's say some generally slept perfectly randomly. So it was possible to identify genes that respond to the cycles are correct and coordinated.
And then scientists sorted out in the molecular background of these hours, says Severinov. - It turned out that the genes identified are so managed by developing certain proteins that at night they accumulate, and in the afternoon fall apart. In fact, such a oscillation of concentration and is a peculiar pendulum in our body. And depending on this, the cell activates various genes, which in the end and manages many processes.
Then scientists found out that exactly the same mechanism works not only in flies, but also in the whole live. He came up with nature to consider time in the body. The practical significance of this discovery is obvious, let's say many mental disorders It is associated with a dream impairment due to failures in the circadian cycles.
Evaluating the award of this premium, a number of specialists already say that this is a "calm award," it will not be an explosion in world science at least because several dozen years ago. Moreover, the awarding of old works becomes a tendency. At the same time, the Nobel Committee has passed past the sensational work on editing the genome, which has become a boom of recent years. "I do not agree with such a thing," says Severinov. "- Editing a genome to get his award to get, and this is not entirely discovery, but rather genetic technique. And cell clock is a real, deep fundamental science, she explains how the world is arranged.
It should be noted that the forecast of Thomson Reuters, which is engaged in the prediction of the laureates since 2002 and most often compared to competitors guess the laureates, this time was mistaken. They put on American scientists who deal with cancer problems.
The award ceremony of laureates will be held by tradition on December 10 on the day of the death of the founder of the Nobel Prizes - the Swedish entrepreneur and the inventor Alfred Nobel (1833-1896). The size of the Nobel Prize in 2017 is nine million Swedish crowns (million US dollars).
Jeffrey Hall was born in 1945 in New York, since 1974 he worked at the University of Brandean, Michael Rosbash was born in Kansas City, also works in the University of Brande, Michael Yang was born in 1945 in Miami, it works at Rockefeller University in New York.
How biological clocks work. What did the Nobel Prize in medicine given in 2017
Jeffrey Hall, Michael Roshbash and Michael Young Website
Three American scientists divided the highest scientific reward for the study of the mechanism of operation of the internal clock in living organisms
Life on Earth is adapted to rotating our planet around the sun. For many years, we have known about the existence within living organisms, including people, biological clocks that help anticipate the daily rhythm and adapt to it. But how exactly do this watch work? American genetics and chronobiologists were able to look inside this mechanism and shed light on his hidden work. Their discoveries explain how plants, animals and people adapt their biological rhythms to synchronize with the daily distribution cycle of the Earth.
Using fruit flies as experimental organisms, the laureates of the Nobel Prize-2017 highlighted the gene, which controls the normal daily rhythm in living beings. They also showed how this gene encodes a protein that accumulates in a cell at night and disintegrate during the day, forcing it, thereby comply with this rhythm. Subsequently, they identified additional protein components that control the mechanism of self-sustaining "clock" inside the cell. And now we know that the biological clock is functioning according to the same principle both inside individual cells and inside multicellular organisms, such as people.
Thanks to the exceptional accuracy, our domestic hours adapt our physiology to such different phases of the day - morning, day, evening and nights. These clock regulate so important functionslike behavior, hormone level, sleep, body temperature and metabolism. Our well-being is suffering when the external environment and internal watches occurs. An example is the so-called Jetlag, which arises from travelers who move from one time zone to another, and then for a long time they cannot adapt to the shift of the day and night. Sleep into the bright time of the day and cannot sleep in the dark. Today there is also a lot of evidence that chronic misband between lifestyle and natural biorhythms increases the risk various diseases.
Our internal clock is impossible to deceive
Experiment Jean-Jacques D "Oruto de Majan Nobel Committee
Most living organisms are clearly adapted to daily change. ambient. One of the first to prevent this adaptation was also proved in the XVIII century French astronomer Jean-Jacques D Oruto de Maran. He watched a mimosa bush and found that her leaves turn over the sun during the day and closed with a sunset. The scientist wondered what would happened if the plant turned out to be in constant darkness? After putting a simple experiment, the researcher discovered that, regardless of availability sunlight, Leaves of experimental mimosa continue to make their usual daily movements. As it turned out, plants have their own internal clock.
Later research has proven that not only plants, but also animals and people are subject to the work of biological clocks that help to adapt our physiology for daily changes. This adaptation is called a circadian rhythm. The term comes from latin words Circa - "Night" and Dies - "Day". But the way these biological watches work, remained a mystery for a long time.
Detection of "watch gene"
In the 1970s, American physicist, biologist and psychogenetic Seymour Benzer, together with his student Ronald Konopkoy investigated whether it is possible to single out genes that control the circadian rhythm in fruit flies. Scientists managed to show that mutations in the gene unknown to them violate this rhythm in experimental insects. They called it the genome of the period. But how did this gene affect the circadian rhythm?
The laureates of the Nobel Prize for 2017 also conducted experiments on fruit flies. Their goal was to open the mechanism of operation of the internal watches. In 1984, Jeffrey Hall and Michael Roshbash, who closely collaborated with each other in the walls of the University of Boston, as well as Michael Young from Rockefeller University in New York successfully isolated a period gene. Hall and Roshbash then found that the PER protein encoded by this genome accumulates cells overnight and destroys the day. Thus, the level of this protein varies during the 24-hour cycle synchronously with a circadian rhythm. The "pendulum" of internal cell clock was discovered.
Self-regulating hourly mechanism
Simplified scheme of work in the cell of proteins that regulate the circadian rhythm Nobel Committee
The next key goal was to understand how these circadian oscillations may occur and supported. Hall and Roshbash suggested that the PER protein during the daily cycle blocks the activity of the period gene. They believed that with an inhibiting feedback loop, the PER protein could periodically prevent its own synthesis and thereby adjust its level in a continuous cyclic rhythm.
To build this curious model lacked only several elements. To block the activity of the period gene, the PER protein produced in the cytoplasm should be achieved by the cell core, which contains genetic material. Hall and Roshkas experiments showed that this protein really accumulates in the core at night. But how does he get there? Answered this question in 1994, Michael Young, who opened the second key "hourly gene", which encodes the TIM protein necessary to comply with the normal circadian rhythm. In simple and elegant work, he showed that when TIM is associated with PER, these two proteins can penetrate into the cell core, where they really block the operation of the period gene to close the inhibitory loop of feedback.
Such a regulatory mechanism explained how this oscillation arose cell proteinbut never closed all questions. For example, it was necessary to establish what controls the frequency of daily oscillations. To solve this task, Michael Young allocated another gene encoding the DBT protein - it delays the accumulation of PER protein. Thus, it was possible to understand how this oscillation is regulated in order to match the 24-hour cycle as accurately as possible.
These discoveries committed by today's laureates underlie the key principles of the functioning of biological watches. In the future, other molecular components of this mechanism were found. They explain the stability of his work and the principle of operation. For example, Hall, Roshbash and Young discovered additional proteins necessary to activate the period gene, as well as a mechanism by which daylight synchronizes the work of biological clock.
Effect of daily rhythms on human life
Cirque Rhythm of the Nobel Committee
Biological watches are involved in many aspects of our complex physiology. Now we know that all multicellular organisms, including people, use similar mechanisms to control circadian rhythms. The work of a large part of our genes is regulated by biological clock, therefore, a carefully configured circidal rhythm adapts our physiology to different phases of the day. Thanks to the fruitful work of three today's nobeliants, the circadian biology has become an extensive and dynamically developing area of \u200b\u200bresearch, which studies the effect of daily rhythms on our health and well-being. And we got another confirmation that at night it is still better to sleep, even if you are a fallen "Owl". It is useful for health.
reference
Jeffrey Hall - Born in 1945 in New York, USA. The doctoral degree was received in 1971 at Washington University (Seattle, Washingon). Until 1973, he held the post of professor in California technological Institute (Pasaden, California). Since 1974, it has been working at the University of Brandea (Waltte, Massachusetts). In 2002, began cooperation with the University of Maine.
Michael Rybach - Born in 1944 in Kansas City, USA. He defended his doctoral in the Massachusetts Institute of Technology (Cambridge, Massachusetts). The next three years was a doctoral enthusiasm to the University of Edinburgh in Scotland. Since 1974, it has been working at the University of Brandea (Waltte, Massachusetts).
Michael Yang. - Born in 1949 in Miami, USA. He graduated from doctoral studies at Texas University (Austin, Texas) in 1975. Until 1977, he passed a post-statement in Stanford University (Palo-Alto, California). In 1978, he joined the teaching staff of the University of Rockefeller in New York.
Translation of materials of the Swedish Royal Academy of Sciences.
Nobel Prize in Physiology and Medicine. Its owners became a group of scientists from the United States. Michael Young, Jeffrey Hall and Michael Rosbash received a reward for the opening of molecular mechanisms controlling the circadian rhythm.
According to the will of Alfred Nobel, the award is awarded that "who will make an important discovery" in this area. The editorial office of the TASS dossier has prepared material on the procedure for awarding this premium and its laureates.
Award award and nomination of candidates
The Nobel Assembly of the Caroline Institute, located in Stockholm, is responsible for awarding the prize. The Assembly consists of 50 professors of the institute. Its worker is the Nobel Committee. It includes five people elected by the Assembly from its members for three years. The Assembly collected several times a year to discuss the applicants selected by the Committee, and on the first Monday of October, the laureate elects a majority vote.
The right to nominate the prize has scientists different countries, including members of the Nobel Assembly of the Caroline Institute and owners of Nobel Prizes on Physiology and Medicine and in Chemistry, which received special invitations from the Nobel Committee. You can offer candidates from September to January 31 of the next year. The premium in 2017 claims 361 people.
Laureaats
The premium is awarded since 1901. The first laureate became german doctor, Microbiologist and immunologist Emil Adolf von Bering, who developed a method of immunization against diphtheria. In 1902, Ronald Ross (UK) studied Ronald Ross (United Kingdom) In 1905, Robert Koh (Germany) examined the pathogens of tuberculosis; In 1923 - Opened Insulin Frederick Banting (Canada) and John Maclaud (United Kingdom); In 1924 - the founder of Electrocardiography by Villem Einthoven (Holland); In 2003, Paul Lotterburg (USA) and Peter Mansfield (United Kingdom) - developed a method of magnetic resonance tomography.
According to the Nobel Committee of the Caroline Institute, until now, the 1945 premium remains the most famous, awarded by Alexander Fleming, Ernesut Chene and Howard Flor (United Kingdom), who opened Penicillin. Some discoveries have lost their importance over time. Among them, the Lobotomy method used in the treatment mental diseases. For its development in 1949, the award was received by the Portuguese Antonou Egash-Monis.
In 2016, the award was awarded to Japanese biologist Yosinari Osumi "For the opening of the Autophagia mechanism" (the process of processing the cell of unnecessary content in it).
According to the Nobel site, today in the list of premium laureates, 211 people, including 12 women. There are two of our compatriots among the laureates: Physiologist Ivan Pavlov (1904; for work in the field of digestive physiology) and biologist and pathologist Ilya Mesnikov (1908; for the study of immunity).
Statistics
In 1901-2016, the premium in physiology and medicine was awarded 107 times (in 1915-1918, 1921, 1925, 1940-1942, the Nobel Assembly of the Caroline Institute could not choose the laureate). 32 times the bonus was divided between two laureates and 36 - between three. Average age laureates 58 years old. The youngest is Canadian Frederick Banting, who received a premium in 1923 at the age of 32, the most elderly - 87-year-old American Francis Peyton Roous (1966).
On 2 October 2017, the Nobel Committee announced the names of the Nobel Prize of 2017 in physiology and medicine. 9 million Swedish crowns will share the American biologists of Jeffrey Hall (Michael Rosbash) and Michael Rosbash (Michael W. Young) for its discovery of the molecular mechanism for the work of biological clock, that is, an infinitely looped circuit rhythm of the life of organisms, including man.
For millions of years, life has adapted to the rotation of the planet. It has long been known that we have internal biological clocks that anticipate and adapt to the time of day. In the evening I want to fall asleep, and in the morning - wake up. Hormones are thrown into the blood strictly on schedule, and the ability / human behavior - coordination, the reaction rate is also dependent on the time of the day. But how do these internal hours work?
The opening of the biological clock is attributed to the French astronome Jean-Jacques de Meran, who in the 18th century noticed that the leaves of mimosa open to the sun during the day and closed at night. He wondered how the plant would behave if placing it in the pitch darkness. It turned out that even in the dark Mimosa followed the plan - she was as if there were an internal clock.
Later, such biorhythms found in other plants, animals and humans. Almost all living organisms on the planet react to the Sun: the circadian rhythm is integrated into the earth's life, in the metabolism of everything alive on the planet. But how this mechanism works - it remained a mystery.
Nobel laureates isolated a gene that controls daylight biological rhythm, Fly Drozofil (a person and flies have a lot of common genes due to the presence of common ancestors). They did his first discovery in 1984. Open gene called period..
Gene period. Codes the PER protein, which accumulates in cells at night and destroys during the day. The PER protein concentration varies on a 24-hour chart according to the circadian rhythm.
They then identified the additional components of the protein and completely disclosed the self-sufficient intracellular mechanism of the circadian rhythm - in this unique reaction of the PER protein blocks the activity of the gene period., That is, PER blocks the synthesis of itself, but gradually collapses during the day (see the circuit at the top). This is a self-sufficient infinitely looped mechanism. It works on the same principle in other multicellular organisms.
After opening the gene corresponding to the protein and the general mechanism of the internal clock, there were still a few more pieces of the puzzle. Scientists knew that the PER protein at night accumulates in the core of the cell. They also knew that the corresponding MRNA was produced in the cytoplasm. It was not clear how the protein falls out of the cytoplasm in the core core. In 1994, Michael Young opened another gene timelesswhich encodes the TIM protein, also necessary for normal work Internal watches. He proved that if Tim joins Per, then the pair of proteins can be carried into the core of the cell, where they block the activity of the gene period.Thus, the close-up endless cycle of the production of PER protein.
It turned out that this mechanism with sophisticated accuracy adapts our internal hours to the time of day. He regulates different critical functions The organism, including human behavior, hormone levels, sleep, body temperature and metabolism. A person feels bad if there is a temporary inconsistency between external conditions and its internal biological clocks, for example, when traveling over long distances in different time zones. There is also evidence that the chronic mismatch of lifestyle and internal watches is associated with increased risk The emergence of various diseases, including diabetes, obesity, cancer and cardiovascular diseases.
Later Michael Young Identified another gene doubleTime., Coding DBT protein, which slows down the accumulation of PER protein in a cage and allows the body to more accurately adapt under 24-hour days.
In subsequent years, the current nobel laureates More details were highlighted in the circadian rhythm of other molecular components, they found additional proteins that participate in the activation of the gene period.And also found out the mechanisms as light helps synchronize biological clock with external environmental conditions.
From left to right: Michael Roshbash, Michael Young, Jeffrey Hall
The study of the internal clock mechanism is still far from completed. We only know the main parts of the mechanism. Circadian biology - the study of internal clock and circadian rhythm - it was separated into a separate rapidly developing direction Research. And all this happened thanks to the three of the current laureates of the Nobel Prize.
Specialists have been discussed for several years that for the molecular mechanism circadian rhythms They will give the Nobel Prize - and this event finally happened.
