FRQ-less oscillators in the circadian system of neurospora

我的研究旨在回答这样一个问题：生物是如何报时的？所有比细菌更大的生物，甚至一些细菌，都有内在的生物钟，在许多生物过程中驱动着日常的节奏。这些“昼夜节律”(大约一天)对人类健康很重要：人类在活动、睡眠和醒来、荷尔蒙、体温等方面都有昼夜节律。驱动这些节律的内部时钟存在于所有高等生物体的单个细胞中，几乎存在于人体的每一个细胞中。当我们遭遇时差或上夜班时，我们会体验到细胞时钟彼此不同步的负面影响。他说，因为内部时钟可以在单个细胞中找到，我们可以用简单的生物体来研究它。我们正在使用一种常见的面包霉菌粗糙脉孢霉作为模式生物，从分子和生化水平上研究时钟的机制。这种真菌在实验室里很容易生长，而且已经研究了60多年，所以我们对它的生物化学和遗传学了解很多。我们使用了扰乱生物钟的突变菌株，我们正在研究这些突变菌株的生物化学，试图确定它们的生物钟被扰乱的原因。其他实验室已经确定了少量在正常时钟机制中重要的基因，但我们发现，即使这些基因有缺陷，真菌仍然可以有节奏。我们使用的是一种在脂类合成方面有异常的突变体，脂类是构成细胞周围膜的脂肪分子。当突变体中一种特定的脂质--二酰甘油的水平很高时，这种真菌的生物钟是有节奏的，即使其他众所周知的生物钟基因发生了突变。已知甘油二酯是动物细胞中的一种重要的信号分子，激活控制许多细胞过程的酶。我们正在研究二酰甘油对脉孢子虫信号酶的影响，以试图了解它是如何影响生物钟的。这项研究可能会帮助我们识别钟表的新成分，这可以帮助我们理解这种真菌，可能还有其他生物，是如何利用它们的生化来报时的。

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.