BIOCHEM ANAL OF WC1--CIRCADIAN RHYTHM/LIGHT TRANSDUCTION

WC1 的生物化学分析--昼夜节律/光传导

• 批准号: 6139975
• 负责人: KWANGWON LEE
• 金额: $ 3.75万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 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/6139975
• 关键词: Drosophilidae; Neurospora; biological signal transduction; circadian rhythms; fungal genetics; fungal proteins; photobiology

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（申请人的摘要逐字复制）：大多数生物都有一个 内部昼夜节律会影响日常活动的许多方面。这 人类昼夜节律的破坏导致了几种节奏 包括睡眠障碍和精神病等疾病，例如躁狂 抑郁和季节性情感障碍。哺乳动物最近的时钟研究 已经揭示了哺乳动物系统中的昼夜节律似乎是基于的 在类似于真菌神经孢子虫和 昆虫果蝇杂物。 细胞振荡器的当前基本范式是转录/ 翻译反馈循环，由负面组成（FRQ 在Neurospora，果蝇和MPER1，MPER2和MPER3中的Per）和 阳性元素（果蝇中的神经孢子，DCLOCK和CYC中的WC1和WC2，以及 哺乳动物中的时钟和bmal1。反馈循环中的关键积极元素 包含PAS结构域，它们形成同型或异质二聚体。 WC1是 远，唯一已知的含PA的蛋白质在光中起着作用 接收和昼夜节律。该应用程序中的研究针对 回答以下问题时：1）FRQ和WC1在 彼此的表情？ 2）WC1复合物的组成部分是什么 恒定的黑暗（可以研究自由运行振荡的地方）和之后 轻脉冲？ 3）PAS域在操作中的重要性是什么 昼夜节律循环和光信号转导？