 Доброе утро. В 2017-м Nobel Prize in Medicine был отмечен к Джейфри Холл, Майкл Росбеш и Майкл Ян для исследований молекарных механизмов, контролируя циркадийный ритм. Но давайте попробуем понять, что это означает для нашей нормальной жизни. У вас ли вы встретили джетлак? Я встретил его довольно часто, потому что, чтобы идти домой, я должен летать от Мюник to Krasnoyarsk, и это 6-часная дифференция в времени между этими два сетей. Поэтому, когда я приезжаю, обычно с утра, уже солнце, но я хочу спать. Конечно, я спал всю ночь через мою трепетку, но в следующие несколько дней я бы хотел спать через деньгами. И мне нужно несколько дней спать. Так что что-то из-за меня не понимает, что я actually moved from Мюник to Krasnoyarsk. И люди говорят, что эти вещи, которые внутри нас, говорят, что это время, сейчас есть циркадийные ритмы. Циркадийные ритмы примерно 24 часа, и это характеристика для многих живых организмов. Это вещи, которые эти организмы работают в зависимости от деньгами. И одна из примеров для таких вещей есть открыть и закрыть флоры планы. Какие-то планы, которые открыли флоры в деньгах, и они закрыли их в ночь, которые make sense, потому что в ночь нет поленейтеров для этих флоры. И это важная вещь о циркадийных ритмах. Они нужны для организмов, чтобы оптимально реагировать к кондиционам environment, которые в зависимости от света и темнота. Наверное, в первом случае, когда циркадийный ритм был описан в деталях, он был сделан по французским исследователям, который был действительно астрономел 300 лет назад. Он работал с плантом, называется Мимоза. И эта плана открылся в деньгах и закрыла их в ночь. И что этот исследователь делал, он поставил Мимоза в ночь, и когда он обзорил, что в ночь планы все еще закрыли, и этот цирк снова и снова открылся в ночь и открылся в деньгах, и закрылся в ночь, но это в полной темноте, он не знает, что это день или ночь. И это значит, что есть что-то внутри плана, которое говорит если это день или ночь, какой-то внутренний цирк. Но что бы это было? Что бы это были физические базы для этого внутреннего цирка внутри нас? Чтобы try to understand it, Let's go to some basics of our life. We know that us these are our genomes. Genomes they bear all information about our body. And genomes they are DNA, and this DNA includes genes. And basically sets of our genes it says who will be us. Some set of genes could make us humans. And some set of genes could make the one fly. And genes they bear information about proteins. And proteins are molecular machines, which perform most of job in our body. So a set of proteins inside a cell it is set of capabilities of a cell to do something. Inside the cell genes are stored in an isolated environment in a nucleus isolated part of the cell. And this makes sense because it's good to store this important information in some safe, isolated environment. But it is also some issue because proteins are synthesized outside this environment in the cytoplasm. So somehow information from genes inside nucleus should be transferred to the cytoplasm. It should be kind of a messenger for that. And it exists. It's actually molecules of RNA which are synthesized on the genes and then when they are transferred to the cytoplasm, they are using information written in them proteins are synthesized. So the one could hypothesize that if we have kind of internal clock, then maybe it could be some genes and proteins for this machine. But how can we find these genes or genes responsible for internal clock? The one could mention the quite easy way to do that. Let's just disrupt all genes one by one. And then look on the animals with these disrupted genes. Maybe they will lose their internal clock. And of course to do the thing like this, it's good to work with some kind of easy kindle animal. And such an animal, for example, is a fruit fly drosophila. We can feed drosophila with a chemical which disrupts DNA and then in the offspring of this drosophila we will be able to find flies with different single genes disrupted. And then we can analyze these flies for their behavior. The good thing about this experiment is actually most of our human genes they are very similar to genes in a fruit fly. And it is quite probable that if we will find some gene responsible for something in a fly human will have the same gene responsible for a very similar function. And this was made by Seymour Benzer and Ronald Kanopka in 1971. Actually they analyzed flies with different genes disrupted for their behavior. They used infrared camera to analyze movements of flies and they generated these kind of tracks for them. So here each track is movements of individual fly and if this is just a straight line it means that fly was not moving and when we have these black peaks it was movement of this fly. And for normal flies we can see characteristic 24-hour pattern. Actually at night they do not move mostly. They move during the daytime when they don't move again at night and so on. This is the normal circadian rhythm of motor activity of these flies. But they find the flies which they are not moving like this. Basically they are asynchronous without this day-night cycle. And they found the gene disrupted in these flies. They called this gene period. Unfortunately Seymour Benzer and Ronald Kanopka could not share Nobel Prize because they died not so far. So okay we have this period gene we know that it is responsible for internal clock. But what does it mean? What does it say to us what is the basis of this internal clock? Let's go to basics again. So period gene is a normal one. So it means that period RNA is synthesized on this gene when it goes to the cytoplasm and period protein is synthesized. Researchers made quite important observation about that. They observed that during the day when it is a light time there is a lot of period RNA but it's almost nothing about period protein. And vice versa at night when it is the darkness it is a lot of period protein in the cells and almost nothing about period RNA. And this observation led to the hypothesis that actually period protein could go back to the nucleus and then it could stay away from its own gene. There is a normal half-life time for each protein and it means that when period gene will be blocked with time period protein will be degraded just by itself by itself it will be disrupted. And then period gene will be active again because period protein will not block it anymore and period RNA will be accumulated again again. This set of events leads to the cycling of period protein concentration in the cells. So during the day concentration of period protein is minimal when it raises at night when it goes down again during the day and this is the basis for our internal clock. And actually period protein can block activity of dozens of other genes and then cycling of period protein concentration leads to the cycling of concentration of dozens of other proteins. And this discovery was made by Jeffrey Hall and Michael Rosbush. The next piece to the slide was added by Michael Young. He discovered another components of the system. He discovered a timeless protein which actually needed for period protein to block activity of period gene. These two proteins act in one complex and they should be together to block activity of the period gene. And this is a quite important component because this timeless protein is an input for light in the system. Because there is another protein Cryptochrome, which is sensitive to light. And then it senses light. Cryptochrome induces disruption of timeless protein. In this case timeless cannot anymore help period protein to block activity of the period gene. Period RNA accumulated again and then this switch to the condition like during the daytime. And the good thing about all of this is that humans have a very similar system. We have also period protein which cycles and which does a basis for our internal clock. So that's the way how I finally adjust to a jet lag actually. But all these discoveries they lead to quite a big paradox. Because it means that each cell in our body has its own internal clock. When billions of clocks in one body, how are we going to be synchronized then? And the answer is actually our brain performs this job. Our eyes are sensitive to light. When the signal about light is transferred to our brain and specific part of our brain called hippocamp synthesize molecules which goes through our body through blood vessels and which noon the clocks in all our cells. And one of the main office molecules is a hormone called melatonin and it was shown that there is cycling of concentration of melatonin in our body dependent of the daytime. Concentration of it is minimal during the day, it races at night when it goes down and so on. And it was shown that proper melatonin cycling is important for general health immune response and our psychological stability. So now we know much more about this our internal clock and these discoveries which were made by Nobel laureates in United States since late 60s to late 90s led us to a big picture of understanding our internal clock from different sites. And knowing all this I would like to say again how it is actually important to sleep a knife during each day the same time to have our external life synchronized with our internal clock. Thank you. I will be happy to answer to your questions. Please raise your hand if you have any. So how about blind people? So I would say that we can distinguish two categories of blind people. There are people who are absolutely blind and they do not feel any light. And when it was studied they still have this internal clock they have cycling of melatonin but it is independent of the light and darkness outside. And that's quite interesting that we have this 24-hour cycle of melatonin cycling of melatonin concentration but completely blind people they have around 25-hour cycle. So still there is something which differ in them from us seeing light but still they have these cycles. And people who are not completely blind they do not see but they still feel some light just. Because the fact that it's some lighting still can adjust the system. And the second question? As far as I understood that this system works like through photoreceptors so what about people living in Canadian countries where they can't find any sun during the whole winter? How is this regulated so far? You know the really exciting thing is that to start with 24-hour circadian rhythms for an animal it's even not needed to be exposed today at night. For example in experiments with flies it was shown that flies living in a complete darkness for generations they still have these 24-hour cycles they do not move mostly 12 hours when they move 12 hours and so on. So cycle is like inside in this protein system and you will have it anyways it's evolutionary concert but if we have light we can adjust this cycle but even if we do not have light it still will be existing. Oh maybe just one question there. You? So when we sleep and we have like the lights on this gets also alters our cycles because our eyes can see still some light this could affect our rhythm cycles. You mean if we have some light when we sleep? Yeah it's going to be bad actually because this system is sensitive to light and even if we got sleeping I guess it will be not a proper sleep actually because you know when we sleep it's of course condition of our brain but also there are physiological processes which should go in parallel with another pressure in our body and so on and these things they are more linked not to the nervous system but to these harmon things and so on but because of light you are going to get not proper suction of melatonin already and then probably you will sleep but physiological processes during this time will not be characteristic for sleeping and then you will not have them during the night and you will not have proper rest afterwards.