The cycle. Cycle also another gene controls that behaviour. These issues all are very important clock genes to control that behaviour. And that this ready Important work is actually followed actually in the mammal, in the mouse. Or people found similar thing, okay? This mainly a few labs for this Drosophila work. But actually, in this one in the mouth is actually the main player is a Japanese researcher Joe Takahashi. Right now, his lab is seen Texas, University of Texas Southwestern. And they found a similar strategy. This strategy seems actually impossible to work. That because here, how can you find the purity gene? Do you just say, maybe we could make the mutants, and then screen a lot of Drosophila. That's quite easy, because the Drosophila is so easy to make the mutant, to maintain. And then you have the high throughput report, actually, a behavior essay, right? So you see, quite easy to find this gene. How about in the main insistor the mouse if you want to make a 1,000 or 10,000 mutants with how many results you need it to have. But actually Joe Takahashi's lab take the effort and then they indeed found, actually a homologue of the gene, also a clock gene they also have [INAUDIBLE], and also they also found. This is a clock gene, also in the mouth and also the clock gene actually has a homologue in the [INAUDIBLE]. And of course this is not a single gene when they found one gene, and later they found more, and more and make the story more complete okay. So what's this gene doing here to control the behavior, circadian? What they found is actually if you make this, I guess it's maybe a Western blot. If you take the animals [INAUDIBLE] and then at a different time point The 24 hours period. A different tempo, you take the animals, okay, and then make it a tissue. And then make a staining to see the peel rate. You will see actually a sunk conditions actually is quite low level, right. And then under these conditions, the level is quite high, and then lower again. So this gene actually turn on actually at a kind of a oscillation of a 24-hour period, okay? So if you see, it's this. This period gene expression, it's a cycle. This cycle is 24 hours. And also, the found, actually the adult genes also is about 24 hours, okay? So your found one gene is oscillating about 24 hours. It's good. Maybe you found the clock. The clock is it turn about 24 hours right. But when you find one gene okay then you wonder okay this is a clock then. Then what controls this gene, because this gene also need oscillation 24 hours then what control this gene right. So then the question is still not believe addressed. By the way you put all these gene together then you form quite interesting. This gene can interfere, because this gene synthesize a protein. The protein can be a transcription factor. And then they can control each other. And most importantly, this gene cause a transcription feedback mechanism. And then for example, there's a period when they exports their protein, and the period came, actually go into the nuclear, and bind to this region and the to inhibitor period expression is neck to feedback loop. And then this one of course then when you have a high level of this period protein what will happen? Imagine, if we have very high level of protein that work, and then this will enter the nuclei will turn off this gene expression. And then you have less and less, the protein, right. And then you will look down When the protein lower down and then this inhibition is released. And then you will turn on the expression. And then you have cycle. Right, and then later the foundation is used to. Actually, like a period. It's not function by itself. You need a partner. The partner is called the Tanis. That is actually, when you have the period synthesized, okay, the protein is there. But this protein cannot be stable. It will be degraded, made first. Only then you have a pattern to turn this, get this team protein and then two can combine together and they can be stable. Okay? Then when they're stable, then they can assimilate, and then they can enter in the nuclei to control the transcription. So this is just the cycle's control. And of course this one in the mammalian system is similar strategy was used. Okay. The most interesting thing is actually these kind of clock genes, concentrated actually in one cell. Okay. So in the brain then you can find some neurons, some particular neuron. That neuron can house all these components there. That means those genes in the single neuron. They can oscillate 24 hours. Then if you interpret this kind of results, then you think, okay. So it's this oscillation in the individual neuron deal with the timing. And then that means those neurons, you can define as the clock neuron. There's a clock in your brain, right? So, these are clock gene and the neuron express all these clock gene, things clock neuron, and then, where is those clock neuron? How can you find it then right now you know the gene. You know the phenotype. Then you need make a new circuitry, right? Of course then quite easy, right? Then you just, yeah, use in-situ to see well just MIA locate all right? And then people found actually. Later I will show you the results. Okay, so this is how the clock system works. Actually by different genes to control each other, especially the transcription. Feedback is the main, the core mechanism for the timing of this different clock coding oscillation.
