New components of the circadian oscillator system of Neurospora

生物钟驱动着生物从单个细胞到整个生物体的所有层次的24小时节律。尽管时钟对人类的日常睡眠/醒来周期、植物的季节性开花、迁徙的蝴蝶的导航能力以及无数其他过程都很重要，但我们仍然不清楚这些时钟在分子水平上是如何工作的。在真核生物中，一组“时钟蛋白”在24小时的反馈循环中开启和关闭特定的基因。多年来，这种“时钟基因反馈回路”一直是关于时钟工作原理的主导观点。然而，当这些反馈环路不起作用时，仍然可以看到一些节奏。我的实验室正在试图找出没有已知反馈环路的时钟是如何工作的，我们正在努力揭露旧想法中的缺陷，并找到新的时钟机制。我们使用真菌粗糙脉孢霉，因为这种生物很容易生长，它已经被研究了很多年，而且它的孢子形成节奏很容易看到。我们已经发现了在没有已知反馈回路的情况下维持节律的重要基因。我们最近发现了由其中两个基因组成的蛋白质的身份，我们想要找出这些蛋白质如何在昼夜节律中发挥作用。一种名为VTOR1的蛋白质帮助细胞调整生长速度，以适应不同的营养供应。另一种蛋白质是Prd-1，它属于一个调节基因表达的家族，但我们还不知道它在粗毛新月形藻中的确切功能。我们知道PRD-1是正常生长对营养的反应所必需的，而蛋白质根据营养改变其在细胞内的位置，因此VTOR1和PRD-1在某种程度上与新陈代谢有关。其他实验室发现，动物体内的生物钟可以调节营养反应，而生物钟也可以通过营养状态来调节。因为我们已经确定了两个涉及生物钟和营养之间相互作用的基因，我们的实验室非常适合使用这个模型系统来促进我们的理解。我们希望这项研究将告诉我们更多关于生物体中的生物钟是如何构成的，以及生物是如何报时的。这将对任何研究细胞如何组织其内部过程的人，以及任何研究生物体如何与日常环境周期相互作用的人都很有用。由于生物钟对人类健康非常重要，这项研究也可能直接为人类福祉做出贡献。

Circadian clocks drive 24-hour rhythms in living things at all levels of organization, from single cells to whole organisms. In spite of the importance of clocks for daily cycles of sleep/wake in humans, seasonal flowering in plants, navigational ability in migrating butterflies, and countless other processes, we still don't know exactly how these clocks work at the molecular level. In eukaryotes, a set of “clock proteins” turns on and off specific genes in a 24-hour feedback loop. This “clock gene feedback loop” has been the dominant idea about how clocks work for many years. However, some rhythms can still be seen when these feedback loops are not functioning. My lab is trying to find out how clocks without the known feedback loops work, and we are in the forefront of the effort to expose the deficiencies in the old idea and find new clock mechanisms. We use the fungus Neurospora crassa because this organism is easy to grow, it has been studied for many years, and its rhythm of spore formation is easy to see. We have discovered genes that are important for maintaining rhythms without the known feedback loop. We have recently discovered the identities of the proteins made by two of these genes, and we want to find out how those proteins function in circadian time-keeping. One protein, VTOR1, helps cells adjust their growth rate to adapt to varying availability of nutrients. The other protein, PRD-1, is in a family that regulates gene expression, but we don't yet know its precise function in N. crassa. We know that PRD-1 is necessary for normal growth responses to nutrients, and the protein changes its intracellular location depending on nutrition, so both VTOR1 and PRD-1 are somehow linked to metabolism. Other labs have found that clocks in animals regulate nutritional responses, and clocks can also be regulated by nutritional states. Because we have already identified two genes involved in interactions between the clock and nutrition, our lab is very well-placed to use this model system to advance our understanding. We expect that this research will tell us more about how daily clocks are constructed in all organisms, and how living things can tell time. This will be useful to anyone studying how cells organize their internal processes, and anyone studying how organisms interact with the daily environmental cycles. Because circadian clocks are very important in human health, this research may also contribute directly to human welfare.