FRQ-less oscillators in the circadian system of Neurospora

我的研究旨在回答这个问题：生物如何告诉时间？所有比细菌大的生物，甚至一些细菌，都有内部时钟，可以驱动许多生物过程的每日节律。这些“昼夜”节律（大约一天）对人类健康很重要：人类在活动、睡眠和清醒、激素、体温等方面都有昼夜节律。当我们遭受时差或夜班时，我们会体验到细胞时钟彼此不同步的负面影响。 由于生物钟存在于单个细胞中，我们可以用简单的生物体来研究它，我们正在用一种常见的面包霉菌--粗糙脉孢菌作为模式生物，从分子和生物化学水平研究生物钟的机制。这种真菌很容易在实验室中生长，并且已经被研究了60多年，所以我们对它的生物化学和遗传学了解很多。我们使用的突变菌株扰乱了生物钟，我们正在研究这些突变菌株的生物化学，试图确定为什么它们的生物钟被打乱。其他实验室已经确定了少数在正常时钟机制中很重要的基因，但我们发现即使这些基因有缺陷，真菌仍然可以有节奏。我们使用的是一种突变体，它在脂质合成方面有异常，脂质分子是构成细胞膜的脂肪分子。当突变体中一种特殊的脂质--甘油二酯--的水平很高时，真菌的生物钟就会变慢，即使其他已知的生物钟基因也发生了突变。已知甘油二酯是动物细胞中重要的信号分子，激活控制许多细胞过程的酶。我们正在研究甘油二酯对脉孢菌中信号酶的影响，试图了解它如何影响生物钟。这项研究可能有助于我们识别钟表机构的新组件，这可以帮助我们了解真菌，以及可能的其他生物体，如何利用它们的生物化学来告诉时间。

My research is aimed at answering this question: How do living things tell time? All living things bigger than bacteria, and even some bacteria, have internal clocks that drive daily rhythms in many biological processes. These "circadian" rhythms (circa diem = about a day) are important in human health: humans have circadian rhythms in activity, sleeping and waking, hormones, body temperature, etc. The internal clocks that drive these rhythms are found in individual cells of all higher organisms and in nearly every cell in the human body. When we suffer from jet lag, or work night shifts, we experience the negative effects of getting our cellular clocks out-of-synch with each other.     Because the internal clock can be found in individual cells, we can use simple organisms to study it. We are using the fungus Neurospora crassa, a common bread mould, as a model organism to study the mechanism of the clock at the molecular and biochemical level. This fungus is easy to grow in the laboratory, and has been studied for more than 60 years, so we know a great deal about its biochemistry and genetics. We use mutant strains that have disrupted clocks, and we are studying the biochemistry of these mutant strains to try to determine why their clocks are disrupted. Other labs have identified a small number of genes that are important in the normal clock mechanism, but we have found that the fungus can still be rhythmic even when these genes are defective. We are using a mutant that has an abnormality in the synthesis of lipids, the fatty molecules that make the membranes around cells. When the level of a particular lipid, diacylglycerol, is high in the mutant, the fungus is rhythmic with a slow clock, even when other well-known clock genes are mutated. Diacylglycerol in known to be an important signalling molecule in animal cells, activating enzymes that control many cellular processes. We are looking at the effects of diacylglycerol on the signalling enzymes in Neurospora to try to understand how it affects the clock. This research may help us identify new components of the clockworks, and this can help us understand how the fungus, and possibly other organisms, use their biochemistry to tell time.