BIOCHEM ANAL OF WC1--CIRCADIAN RHYTHM/LIGHT TRANSDUCTION

描述(申请人摘要逐字复制)：大多数生物都有一个 内部生物钟，影响日常活动的许多方面。这个 人体生物钟的紊乱导致了几种节律 障碍包括睡眠障碍和精神疾病，如躁狂 抑郁症和季节性情感障碍。哺乳动物的最新时钟研究 揭示了哺乳动物系统中的生物钟似乎是基于 根据类似于在真菌中建立的范例，粗糙脉孢菌和 昆虫黑腹果蝇。 目前细胞振荡器的基本范例是转录/ 翻译反馈环，由负(FRQ)组成 在脉孢子虫中，果蝇中的PER和哺乳动物中的mPER1、mPER2和mPER3)和 阳性成分(脉孢子虫中的WC1和WC2，果蝇中的dCLOCK和CyC，以及 哺乳动物中的Clock和BMAL1)。反馈循环中的关键积极因素 含有PAS结构域，它们通过这些结构域形成同二聚体或异二聚体。Wc1是，所以 到目前为止，唯一已知的含有PAS的蛋白质在光和光中都起作用 接收和昼夜节律。对这一应用的研究旨在 在回答以下问题时：1)FRQ和WC1在 彼此的表达方式？2)中Wc1复合体的组成部分是什么 恒定黑暗(可以研究自由振荡的地方)，并且在 光脉冲？3)PAS域在操作中的意义是什么 昼夜节律反馈环和光信号转导？

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?