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BIOCHEM ANAL OF WC1--CIRCADIAN RHYTHM/LIGHT TRANSDUCTION

WC1 的生物化学分析--昼夜节律/光传导

基本信息

批准号：
6385196
负责人：
KWANGWON LEE
金额：
$ 4.2万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-09-01 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/6385196
关键词：
Drosophilidae Neurospora biological signal transduction circadian rhythms fungal genetics fungal proteins photobiology

项目摘要

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?

描述（逐字复制申请人的摘要）：大多数生物体都有一个内部生物钟影响日常活动的许多方面。这人类生物钟的破坏会导致多种节律性疾病，包括睡眠障碍和精神疾病，例如躁狂症抑郁症和季节性情感障碍。最近的哺乳动物时钟研究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式和昆虫果蝇。当前细胞振荡器的基本范例是转录/ 平移反馈环路，由负反馈环路（FRQ 脉孢菌属中的 PER，果蝇中的 PER 以及哺乳动物中的 mPER1、mPER2 和 mPER3）以及阳性元件（脉孢菌中的 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，通过它们形成同源或异源二聚体。 WC1是，所以迄今为止，唯一已知的含 PAS 的蛋白质在光和光下都发挥作用接收和昼夜节律。本申请的研究目的是回答以下问题： 1) FRQ 和 WC1 在彼此的表情？ 2) WC1复合体由哪些成分组成恒定黑暗（可以研究自由振荡）并且经过一段时间后光脉冲？ 3）PAS域在运行中有何意义昼夜节律反馈回路和光信号传导？