BIOCHEM ANAL OF WC1--CIRCADIAN RHYTHM/LIGHT TRANSDUCTION

描述（申请人的摘要逐字复制）：大多数生物体具有 内部生物钟影响日常活动的许多方面。的 人体生物钟的破坏导致了几种节律性 包括睡眠障碍和精神疾病，如躁狂症 抑郁症和季节性情感障碍哺乳动物生物钟研究进展 揭示了哺乳动物系统中的生物钟似乎是基于 基于类似于真菌粗糙脉孢菌中建立的范例， 果蝇 细胞振荡器的当前基本范例是转录/ 平移反馈环，由负反馈（FRQ）组成 在脉孢菌属中，在果蝇属中的PER和在哺乳动物中的mPER 1、mPER 2和mPER 3）， 阳性元件（脉孢菌属的WC 1和WC 2，果蝇属的dCLOCK和CYC， 哺乳动物中的CLOCK和BMAL 1）。反馈循环中的关键积极因素 含有PAS结构域，通过PAS结构域，它们形成同源或异源二聚体。WC 1是，所以 迄今为止，唯一已知的含有PAS的蛋白质，在光 接收和昼夜节律。该应用的研究目的是 在回答以下问题时：1）FRQ和WC 1在 对方的表情？2)WC 1复合体的组成部分是什么？ 恒定黑暗（其中可以研究自由运行振荡），并且在 光脉冲？3)PAS域在操作中的重要性是什么？ 昼夜节律反馈回路和光信号转导？

DESCRIPTION (Applicant's abstract reproduced verbatim): Most organisms have an internal circadian clock which influences many aspects of daily activities. The disruption of the circadian clock in humans leads to several rhythmicity disorders including sleep disorders and psychiatric illnesses such as manic depression and Seasonal Affective Disorder. Recent clock studies in mammals have revealed that the circadian clock in mammalian systems appears to be based upon a paradigm similar to that established in the fungus Neurospora crassa and the insect Drosophila melanogaster. The current basic paradigm for the cellular oscillator is a transcriptional/ translational feedback loop, which is composed of negative (FRQ in Neurospora, PER in Drosophila and mPER1, mPER2 and mPER3 in mammals) and positive elements (WC1 and WC2 in Neurospora, dCLOCK and CYC in Drosophila, and CLOCK and BMAL1 in mammals). The key positive elements in the feedback loop contain PAS domains, through which they form homo- or hetero-dimers. WC1 is, so far, the only known PAS-containing protein that plays a role both in light reception and in circadian rhythms. The research in this application is aimed at answering the following questions: 1) What are the roles of FRQ and WC1 in each other's expression? 2) What are the components of the WC1 complex in constant dark (where the free running oscillation can be studied) and after a light pulse? 3) What is the significance of the PAS domain in the operation of the circadian feedback loop and in the light signal transduction?