Hi everybody. Welcome to the wrap-up to Lecture 6. My name is Cornelia Madeti. I'm a post-doc in this institute and one of your teaching assistants. With me, here today are Neda Ghotbi, doctoral student in the institute, Joana Matera, also doctoral student in the institute, and LuÃsa Pilz, also a doctoral student in the institute, and Martha Merrow, whom you know as one of your instructors in our lectures. >> So, where do we start? >> I think- >> With the first question. >> With the first question. [LAUGH] >> And I actually have that. If you think about people who have to live against their clock, for example shift workers. Is it best to preserve your natural rhythm or is it better to adapt it to your shift that you are actually working? >> Yes, so I can answer that question because that is what my thesis is about. About shift work research. And that really depends on the shift schedule you're working in. So if you work on a rotational schedule, it makes more sense to stay within your natural rhythm and not to adjust to each shift. But if you have a permanent shift scheduled then it makes more sense for you adjust to your shift schedule, in terms of sleep and light behavior. So that you also try to stay with that rhythm during your free days, which is very important. So that you do not switch back and forth again during work and free days. >> So you make it sound so easy, but of course we've had so many discussions about this in the institute in the past because of this really trivial problem that as soon as shift workers go outside during the day, when they're trying to keep their entrained phase maybe to a later phase or to a night time phase, then they get so much more light in the day just by a short excursion outside than they would have gotten from artificial light over night. So, do you have any tricks or strategies you can mention that might help people to keep the balance of their light exposure to favor a new entrained phase. >> So, yes, there are recommendations. What you can do, for example, you can wear sunglasses after a night shift when the sun is already up. You can just put on sunglasses, which will block out the blue light. So that you don't get this circadian active light in the morning. And of course, you can sit in front of these very high and strong artificial lamps where you can experience big amount of light. >> Mm-hm. >> And you can schedule that in terms of adjusting to a later schedule. That you can get light when your circadian system needs it, in order to adjust properly to the shift. >> Finally, a way that we can use the computer late at night. >> Yes, for a shift worker, it could be even beneficial. >> Helpful. >> So, Joana , are there actually some shifts that fit certain chronotypes better than others? >> Mm-hm, yes there are. So, for early chronotypes, where we see naturally a very early bed time and very early wake up time, we see that this suits perfectly to morning shifts. Where as the reverse is seen in later chronotypes. You have very late bed-times, not so very late wake-up times, and this fits very good to the late working times over the night shift. >> So in the lecture, I referred to this question about whether sleep disruption and depression is upstream or downstream of the clock? Are there some other examples that you guys have read about that a that address this idea of how the circadian clock or sleep patterns are tied into neuro-pathologies? >> Well, circadian and sleep disruption are actually common features of neuro-psychiatry disorders, including schizophrenia and bi-polar disorder and major depressive disorder. What is still unclear is if they are just symptoms or rather triggers or contributing factors to these disorders. There is also the possibility of a snowball-effect! So, a circadian or sleep disturbance leading to, or contributing to the etiology of a neuro-psychiatric disorder, depression for example, which by themselves aggravate the sleep condition. >> And that would also relate to the hen and egg problem that we talked about before where you sometimes cannot distinguish is the psychiatric disorder beforehand, >> Mm-hm. >> because of the circadian clock or the other way around? >> Exactly, exactly. >> Mm-hm. >> So it might be worth thinking about why we think that depression might be linked to the circadian clock in the first place! I talked a little bit about that neuro-transmitters could be disrupted if sleep was disrupted but of course there are much stronger connections. So, for instance, major depression has a big peak in the Spring and also in the Fall, in terms of the severity of the symptoms. And then, of course, seasonal affective disorder, a depressive syndrome that occurs as the photoperiods are getting shorter in the Fall and disappears almost as soon as the photoperiods start to increase again in the middle of the Winter time has obviously a strong seasonal component to that, as its name implies. And so, since seasonality is intimately tied to circadian biology, there's some indication that the circadian clock will be involved in this pathology also. >> Okay, so we said a little about clock genes in a normal population. >> Mm. >> Why? >> Yes, that's a good point. So I've mentioned a couple of times that we are pretty sure, we're on the right track for what the human clock genes are based on some spontaneous mutations and big pedigrees that we discovered. And indeed then the follow-up studies that looked at what normal polymorphisms in the population were associated with changes in sleep timing have been much less successful. So this institute has been involved in some of that work and indeed we did not find anything except for a gene that was involved actually in sleep duration. And I think others have had similar experiences, in that we haven't really found, robustly found, which clock gene polymorphisms are associated with sleep timing. That said, there are several studies that come up with Per-3 as a candidate for having something to do with sleep >> Mm-hm. >> and sleep structure perhaps. And then there also are studies that sometimes go in the direction of suggesting that the Clock gene has some polymorphisms that are associated with sleep timing. There also are studies that don't confirm those findings. >> Mm-hm. >> And so, these are probably right on the border of being significant. And the way I interpret that is that this is a phenotype of small effects on one hand, -We know that sleep timing is a heritable trait in humans, so there is a contribution from genes.- but on the other hand, I think, there are so many little polymorphisms that are involved that you rarely get something like a clear Mendelian inheritance, and you rarely get a strong phenotype that you can find back with gene association studies, that's my interpretation. And the clock is known that there are many things that are of small effect or that involve many polymorphisms. So, the clock is just one more problem to tackle once we have better tools that will help us in that direction. >>So, what other questions ww did not cover, or we could have covered more in this course? >> Oh, mm. >> I think I know something. >> [CROSSTALK] Yeah, yes? >>How about parasites and clocks? So this idea of two interacting clocks and >> Mm-hm. >> what they do to each other? Who is first, who determines what is the outcome of that? >> Mm-hm. >> That would compliment very nicely some work on actually social clocks that´s been done >> Mm-hm. by some of our colleagues. And for instance, two mutant species when they are put together, what happens? >>Mm-hm. >>But I think that's really going to be an emerging field. I felt that there was a big hole with circadian neurobiology, because this is really, >> Mm-hm. >> of course for behaviour, where so much of it is at. And there's, some beautiful, elegant work out there. And I hope that some of the colleagues will follow that up with the next Coursera course. That would be a great topic, I think. >> Yeah, and we also, just talked about circadian clocks, right? So, but there are so many other clocks out there. For instance, a annual clock or ultradian clocks,. >> Yeah. >> You could also discuss. >> Yeah. Yeah, I think that's an also great idea. I mean, annual clocks have a huge importance for all kinds of agriculture, and so forth. >> Mm. >> This is really an interesting topic. For that matter, we focused I think on, mammalian findings with a few references to some of the other model systems like the prokaryotic model system and the plants and the flies and the fungal systems. >> Mm-hm. >> And, it really, each one of those has just a rich body of literature and experimentation that goes behind it so. >> Mm-hm. >> Oh, we could only scratch the surface here. >> Yes, and we didn't even mention the ones that are really living in some very extreme niches. >> Yeah, that, yeah. >> Like cave fish, or >> Yes, yes. >> Or the reindeer. >> Reindeer [CROSSTALK]. >> Yes. Yes, above the Arctic circle, indeed. >> Yes. And that would actually go very nicely into an ecological approach of studying circadian rhythms. >> Mm-hm. >> I think from our side, we know that there are a lot of real interesting molecular mechanisms that are emerging and developing every month when you pick up something new. I think something that's going to be really taking off in the future is non-coding RNAs >> Mm-hm. >> regulating this at the transcriptionial level. >> Mm-hm. How 'bout epigenetics at the clock. >> Yes. >> I think- >> Yes, yes, absolutely. >> Mm-hm. >> Yes. >> Yes? >> That's been a major theme the last couple of years and, it's still a wide open question. >> That's true. Yes. >> So we also talked a lot about light entraining the circadian clock, but we don't talk too much about others zeitgebers that >> Yes. >> can give signs to the clock. Like for example, food. >> You know, we touched on how food entrains the liver, but we didn't touch on, for instance, this fascinating problem that's been described with the food-entrainable oscillator. When you take out the SCN, you can actually then use food to entrain behaviour, and that actually seems to have some of the same characteristics of our SCN and light entrained circadian clocks. So, this is also a very interesting puzzle. that could be described. >> Did we go into depth about seasonality? >> No. We really also just scratched the surface and that's also been something that's been very hot the last years with a lot more progress being made on this concept of morning and evening oscillators. So how we can entrain differently at different times of years. >> Mm-hm. >> Yeah, and since we know that not only the circadian component but also sleep homeostasis regulates the timing of sleep, this would also be very interesting to discuss this whole sleep research field and circadian biology. >> That's a huge subject, of course. >> Yes. Sleep. Yes, this is it's own mammoth field. It's huge and very important, obviously. We always say that we spend a third of our life sleeping and we actually know pretty little about it. The whys and the hows. So, anything else? No, I think we've gone through a pretty good list of things >> Mm-hm. >> That I hope, of course,... We just admitted some of our flaws and deficiencies. But, we can't talk about everything in a six-week course. And maybe we've given the students some ideas of how to go on and research projects to think about and what to study next? All those things. So, I guess we are at the end now. I need to thank you all and, of course, we thank the students who have stuck with us until the very end. And now it's time to drink some nice German beer. >> Finally. >> And we say Prost [SOUND]. >> Prost. >> [LAUGH]. >> Prost. >> Cheers. Cheers. [SOUND]
