Nobel Laureates in Physiology or Medicine. Nobel Prize in Physiology or Medicine

The announcing of the winners of the Physiology or Medicine Prize kicked off the annual Nobel Week in Stockholm on Monday. stated that the 2017 award honored researchers Michael Rosbash and Michael Young for

the discovery of molecular mechanisms that control circadian rhythms - cyclical fluctuations in the intensity of various biological processes associated with the change of day and night.

Life on Earth is adapted to the rotation of the planet. It has long been established that all living organisms, from plants to humans, have a biological clock that allows the body to adapt to changes in the environment during the day. The first observations in this area were made at the beginning of our era, more thorough research began in the 18th century.

By the 20th century, the circadian rhythms of plants and animals had been studied quite fully, but it remained a secret how exactly the "internal clock" works. This secret was discovered by American geneticists and chronobiologists Hall, Rosbash and Young.

Fruit flies have become a model organism for research. A team of researchers was able to find in them a gene that controls biological rhythms.

Scientists have found that this gene encodes a protein that accumulates in cells during the night and is destroyed during the day.

Subsequently, they identified other elements responsible for the self-regulation of the "cell clock" and proved that the biological clock works in a similar way in other multicellular organisms, including humans.

The internal clock adapts our physiology to completely different times of the day. Our behavior, sleep, metabolism, body temperature, hormone levels depend on them. Our well-being worsens when there is a discrepancy between the work of the internal clock and environment... So, the body reacts to a sharp change in the time zone with insomnia, fatigue, headache. Time zone change syndrome, jetlag, has been included in the International Classification of Diseases for several decades. The discrepancy between the lifestyle and the rhythms dictated by the body leads to an increased risk of developing many diseases.

The first documented experiments with internal clocks were carried out in the 18th century by the French astronomer Jean-Jacques de Meran. He found that the leaves of mimosa sagged at nightfall and spread again in the morning. When de Meran decided to test how the plant would behave without access to light, it turned out that the mimosa leaves rose and fell regardless of the lighting - these phenomena were associated with a change in the time of day.

Later, scientists found out that other living organisms also have similar phenomena that adjust the body to changes in conditions during the day.

They were called circadian rhythms, from the words circa - "around" and dies - "day." In the 1970s, physicist and molecular biologist Seymour Benzer wondered if the gene that controls circadian rhythms could be identified. He managed to do this, the gene was named period, but the control mechanism remained unknown.

In 1984, Hall, Roybash and Young managed to recognize him.

They isolated the required gene and found that it is responsible for the accumulation and destruction of the associated protein (PER) in cells, depending on the time of day.

The next task of the researchers was to understand how circadian oscillations arise and are maintained. Hall and Rosbash hypothesized that protein accumulation blocks gene function, thereby regulating the protein content in cells.

However, in order to block the work of a gene, a protein produced in the cytoplasm must reach the cell nucleus, where the genetic material is located. It turned out that PER is really embedded in the kernel at night, but how does it get there?

In 1994, Young discovered another gene, timeless, that encodes the TIM protein required for normal circadian rhythms.

He found that when TIM binds to PER, they are able to penetrate the cell nucleus, where they block the period gene through feedback inhibition.

But some questions still remained unanswered. For example, what controlled the frequency of circadian oscillations? Young later discovered another gene, doubletime, which is responsible for the formation of the DBT protein, which delayed the accumulation of the PER protein. All of these discoveries helped to understand how fluctuations are adapted to the 24-hour daily cycle.

Subsequently, Hall, Roybash and Young made several more discoveries, complementing and clarifying the previous ones.

For example, they identified a number of proteins required to activate the period gene, and also discovered the mechanism by which the internal clock is synchronized with light.

The most likely contenders for Nobel prize in this area were named virologist Yuan Chang and her husband, an oncologist, who discovered the herpes virus type 8 associated with Kaposi's sarcoma; Professor Lewis Cantley, who discovered the signaling pathways of the enzymes phosphoinositide-3-kinases and studied their role in tumor growth; and a professor who made a significant contribution to the analysis of data obtained by methods of brain imaging.

In 2016, the laureate of the Japanese Yoshinori Osumi prize for the discovery of the mechanism of autophagy - the process of degradation and recycling of intracellular waste.

Life on Earth obeys the 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 managed to calculate the 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 that regulates 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 with the time of day. Since the discoveries of Hall, Rosbash and Young, a lot of data have appeared on how sharp or constant deviations in the way of life from the given "biological clock" can be dangerous to health.

The first evidence that living things have a "sense of time" appeared in the 18th century: then the French naturalist Jean-Jacques d "Hortu de Meran showed that mimosa continues to open flowers in the morning and close in the evening, even being in the dark around the clock. showed that not only plants, but also animals, including humans, feel the time of day.The periodic change of 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 Bentzer and his student Ronald Konopka found a gene that controls circadian rhythms in fruit flies, and forced its period. In 1984, Jeffrey Hall and Michael Rosbash at Brandelis University in Boston and Michael Young of Rockefeller University in New York isolated the gene period, and then Hall and Rosbash figured out what the protein encoded in it, PER, does - and it accumulates in the cell at night and is spent all day, so you can judge the time of day by its concentration.

This system, as Hall and Rosbash suggested, 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. It remained only to answer the question of how the protein enters the cell nucleus - after all, only there it can influence the activity of the gene.

In 1994, Young discovered a second important gene for circadian rhythms, the timeless gene, which encodes a TIM protein that 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 stretches for 24 hours. In subsequent years, many other genes and proteins were discovered - parts of the delicate mechanism of the "biological clock", including those that allow you to "turn the arrows" - proteins, the activity of which depends on illumination.

Circadian rhythms regulate various aspects of our body's life, including at the genetic level: some genes are more active at night, some during the day. The discoveries of the 2017 laureates have expanded the biology of circadian rhythms into a vast scientific discipline; dozens are written every year scientific works about how the "biological clock" is arranged in different types, including a person.

According to the website of the Nobel Committee, having studied the behavior of fruit flies in different phases of the day, researchers from the United States were able to look inside the biological clock of living organisms and explain the mechanism of their work.

72-year-old geneticist Jeffrey Hall from the University of Maine, his 73-year-old colleague Michael Rosbash from private Brandeis University, and 69-year-old Michael Young, who works at Rockefeller University, have figured out how plants, animals and people adapt to the change of day and night. Scientists have found that circadian rhythms (from Latin circa - "about", "around" and Latin dies - "day") are regulated by the so-called period genes, which encode a protein that accumulates in the cells of living organisms at night and is consumed during the day.

2017 Nobel laureates Jeffrey Hall, Michael Rosbash and Michael Young began investigating the molecular biological nature of living organisms' internal clocks in 1984.

“The body clock regulates behavior, hormone levels, sleep, body temperature and metabolism. Our well-being is impaired if there is a mismatch between the external environment and our internal biological clock - for example, when we travel across several time zones. Nobel laureates found signs that a chronic inconsistency between a person's lifestyle and biological rhythm, dictated by the internal clock, increases the risk of various diseases, "- says the website of the Nobel Committee.

Top 10 Nobel Laureates in Physiology and Medicine

There, on the website of the Nobel Committee, there is a list of the ten most popular laureates of the prize in the field of physiology and medicine for the entire time that it has been awarded, that is, since 1901. This rating of Nobel Prize winners was compiled by the number of views on the pages of the site dedicated to their discoveries.

On the tenth line- Francis Crick, British molecular biologist who won the Nobel Prize in 1962 with James Watson and Maurice Wilkins “for discoveries concerning the molecular structure of nucleic acids and their importance for the transmission of information in living systems,” in other words, for the study of DNA.

On the eighth line the ranking of the most popular Nobel laureates in the field of physiology and medicine is the immunologist Karl Landsteiner, who received the prize in 1930 for the discovery of blood groups in humans, which made blood transfusion a common medical practice.

In seventh place- Chinese pharmacologist Tu Yuyu. Together with William Campbell and Satoshi Omura, she received the Nobel Prize in 2015 “for discoveries in the field of new ways of treating malaria,” or rather for the discovery of artemisinin, a drug made from wormwood that helps fight this infectious disease. Note that Tu Yuyu became the first Chinese woman to be awarded the Nobel Prize in Physiology or Medicine.

In fifth place Japan's Yoshinori Osumi, winner of the 2016 Physiology and Medicine Prize, is on the list of the most popular Nobel laureates. He discovered the mechanisms of autophagy.

On the fourth line- Robert Koch, German microbiologist who discovered the bacillus anthrax, cholera vibrio and tubercle bacillus. Koch received the Nobel Prize for his research on tuberculosis in 1905.

On the third place The ranking of Nobel Prize winners in physiology and medicine is the American biologist James Dewey Watson, who received the award along with Francis Crick and Maurice Wilkins in 1952 for the discovery of the structure of DNA.

Well and most popular Nobel laureate In the field of physiology and medicine, Sir Alexander Fleming, a British bacteriologist, who, along with colleagues Howard Florey and Ernst Boris Cheyne, received the award in 1945 for the discovery of penicillin, which truly changed the course of history, turned out to be.

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 work of the hormonal system, body temperature and other parameters of the human body, which vary depending on the time of day. Read more about the discovery of scientists - in the material RT.

Winners of the Nobel Prize in Physiology or Medicine Reuters Jonas Ekstromer

The Nobel Committee of the Karolinska Institute in Stockholm on Monday, October 2, announced that the 2017 Nobel Prize in Physiology or Medicine was awarded to American scientists Michael Young, Jeffrey Hall and Michael Rosbash for discovering the molecular mechanisms that control circadian rhythm.

"They were able to get inside the body's biological clock and explain how it works," the committee said.

Circadian rhythms are the cyclic fluctuations of various physiological and biochemical processes in the body associated with the change of day and night. In almost every organ of the human body, there are cells with an individual molecular clock mechanism, and therefore, circadian rhythms are a biological chronometer.

According to the release of the Karolinska Institute, Young, Hall and Rosbash managed 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 work of this mechanism, and understand the work of the independent mechanics of this phenomenon inside each individual cell. We now know that the biological clock works the same way in the cells of other multicellular organisms, including humans, ”the awarding committee said in a release.

• Fruit fly
• globallookpress.com
• imagebroker / Alfred Schauhuber

The presence of a biological clock 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 illumination from receptors on the retina and sends a signal to other organs using nerve impulses and hormonal changes.

In addition, some cells of the nucleus, like cells of other organs, have their own biological clock, the work of which is provided by proteins, the activity of which varies depending on the time of day. The synthesis of other protein bonds that generate circadian rhythms of life depends on the activity of these proteins. individual cells and whole organs. For example, staying in a brightly lit room at night can shift the circadian rhythm, activating the protein synthesis of 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 is only available during the day, their liver circadian cycle shifts by 12 hours.

The rhythm of life

Circadian rhythms are diurnal 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 is not a discovery of yesterday or today. These studies have been carried out for many decades - from the 80s of the last century to the present - and have made it possible to discover one of the deepest mechanisms that regulate the nature of the human body and other living beings. The mechanism discovered by scientists is very important for influencing the body's circadian rhythm, ”Melnikov said.

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According to the expert, these processes occur not only due to the change of day and night. Even in the polar night conditions, the diurnal rhythms will continue to operate.

“These factors are very important, but very often they are violated in people. These processes are regulated at the gene level, which was confirmed by the laureates of the award. Nowadays, people very often change time zones and are exposed to various stresses associated with abrupt changes in circadian rhythm. Intense rhythm modern life can affect the correctness of regulation and the possibility of resting the body, ”concluded Melnikov. He is confident that the study of Young, Hall and Rosbash provides an opportunity for the development of new mechanisms for influencing the rhythms of the human body.

Prize history

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 in the world. The University's Nobel Committee consists of five permanent members, who, in turn, have the right to invite experts for consultations. The list of nominees for this year's award numbered 361 names.

The Nobel Prize in Medicine has been awarded 107 times to 211 scientists. Its first laureate was in 1901 the German physician Emil Adolph von Bering, who developed a method of immunization against diphtheria. The Committee of the Karolinska Institute considers the most significant prize in 1945, awarded to the British scientists Fleming, Cheyne and Flory for the discovery of penicillin. Some prizes have become irrelevant over time, such as the one awarded in 1949 for the development of the lobotomy method.

In 2017, the amount of the award was increased from 8 million to 9 million Swedish kronor (about $ 1.12 million).

The ceremony of awarding the laureates will traditionally take place on December 10 - the day of the death of Alfred Nobel. The prizes in physiology and medicine, physics, chemistry and literature will be presented in Stockholm. The Peace Prize, according to the Nobel's will, is awarded on the same day in Oslo.

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Nobel Prize in Physiology or Medicine. A group of scientists from the United States became its owners. Michael Young, Jeffrey Hall and Michael Rosbash received an award for their discovery of the molecular mechanisms that control circadian rhythm.

According to the testament of Alfred Nobel, the prize is awarded to the one "who makes important discovery"in this area. The editorial staff of TASS-DOSSIER prepared material on the procedure for awarding this prize and its laureates.

Awarding the Prize and Nominating Candidates

The Nobel Assembly of the Karolinska Institute, located in Stockholm, is responsible for awarding the prize. The assembly consists of 50 professors from the institute. Its working body is the Nobel Committee. It consists of five people, elected by the Assembly from among its members for a three-year term. The Assembly meets several times a year to discuss the candidates selected by the committee, and on the first Monday of October, by a majority vote, elects the laureate.

Scientists are eligible to nominate for the award different countries, including members of the Nobel Assembly of the Karolinska Institute and the winners of the Nobel Prizes in Physiology or Medicine and Chemistry, who received special invitations from the Nobel Committee. You can propose candidates from September until January 31 of the next year. 361 people are nominated for the award in 2017.

Laureates

The prize has been awarded since 1901. The first laureate was the German physician, microbiologist and immunologist Emil Adolph von Bering, who developed a method of immunization against diphtheria. In 1902, Ronald Ross (Great Britain), who studied malaria, received the award; in 1905 - researcher of tuberculosis pathogens Robert Koch (Germany); in 1923, Frederick Bunting (Canada) and John McLeod (Great Britain) discovered insulin; in 1924 - the founder of electrocardiography Willem Einthoven (Holland); in 2003 - Paul Lauterbur (USA) and Peter Mansfield (UK) who developed the method of magnetic resonance imaging.

According to the Nobel Committee of the Karolinska Institute, the 1945 prize, awarded to Alexander Fleming, Ernest Cheyne and Howard Flory (Great Britain), who discovered penicillin, remains the most famous. Some discoveries have lost their significance over time. Among them is the lobotomy method used in the treatment of mental illness. For its development in 1949 the prize was received by the Portuguese Antonio Egas-Moniz.

In 2016, the prize was awarded to the Japanese biologist Yoshinori Osumi "for the discovery of the mechanism of autophagy" (the process of the cell processing unnecessary content in it).

According to the Nobel website, there are 211 people on the list of laureates, including 12 women. Among the laureates are two of our compatriots: physiologist Ivan Pavlov (1904; for work in the field of physiology of digestion) and biologist and pathologist Ilya Mechnikov (1908; for research on immunity).

Statistics

In 1901-2016, the prize in physiology and medicine was awarded 107 times (in 1915-1918, 1921, 1925, 1940-1942, the Nobel Assembly of the Karolinska Institute could not choose a laureate). The prize was divided 32 times between two laureates and 36 times between three. The average age of the laureates is 58 years. The youngest is Canadian Frederick Bunting, who won the award in 1923 at the age of 32, the oldest is 87-year-old American Francis Peyton Rose (1966).