New components of the circadian oscillator system of Neurospora

从单细胞到整个生物体，生物时钟驱动着各个层次生物的24小时节律。尽管时钟对人类的日常睡眠/觉醒周期、植物的季节性开花、迁徙蝴蝶的导航能力以及无数其他过程都很重要，但我们仍然不知道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小时的反馈循环中打开和关闭特定基因。多年来，这种“时钟基因反馈循环”一直是关于时钟如何工作的主流观点。然而，当这些反馈回路不起作用时，仍然可以看到一些节奏。我的实验室正试图找出没有已知反馈回路的时钟是如何工作的，我们站在揭露旧思想缺陷和寻找新时钟机制的努力的最前沿。我们使用粗神经孢子菌，因为这种生物容易生长，它已经被研究了很多年，它的孢子形成的节奏很容易看到。我们已经发现了在没有已知反馈回路的情况下维持节奏的重要基因。我们最近发现了由其中两个基因组成的蛋白质的特性，我们想要找出这些蛋白质在昼夜节律中是如何起作用的。一种名为VTOR1的蛋白质帮助细胞调整生长速度，以适应营养物质的变化。另一种蛋白质，PRD-1，属于一个调节基因表达的家族，但我们还不知道它在N. crassa中的确切功能。我们知道，PRD-1对于营养物质的正常生长反应是必需的，蛋白质根据营养改变其细胞内位置，因此VTOR1和PRD-1都与代谢有关。其他实验室发现，动物体内的生物钟可以调节营养反应，而生物钟也可以受到营养状态的调节。因为我们已经确定了参与生物钟和营养之间相互作用的两个基因，我们的实验室非常适合使用这个模型系统来推进我们的理解。我们期望这项研究将告诉我们更多关于所有生物的日常时钟是如何构建的，以及生物是如何识别时间的。这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循环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有助于人类福利。

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.