Identification of the circadian clock proteome

描述(由申请人提供)：这项建议的长期目标是确定参与调控哺乳动物时钟基因表达的昼夜节律模式的组件和机制。哺乳动物的生物钟蛋白存在于巨大的复合体中，这些复合体的组成在一天的不同时间都不同。基于蛋白质组学的方法将被用来在体外细胞环境中识别结合在这些复合体中的未知蛋白质。识别的蛋白质将被评估体内的相互作用，以确认识别的相互作用是生物相关的。然后将确定哺乳动物生物钟内生物相互作用蛋白的功能和必要性。因此，这项工作将发现新的生物钟蛋白，它们可能作为治疗靶点来改善与时钟相关的疾病(如时差、轮班工作)和更严重的疾病，如昼夜节律睡眠障碍和其他与时钟相关的心理障碍(如季节性情感障碍)。

DESCRIPTION (provided by applicant): The long-term goal of this proposal is to identify the components and mechanisms involved in regulating circadian patterns of clock gene expression in mammals. Mammalian circadian clock proteins are found in huge complexes, that differ in composition at various times of day. A proteomics based approach will be used to identify unknown proteins bound in these complexes, in an in vitro cellular context. Identified proteins will be evaluated for in vivo interactions to confirm the identified interactions are biologically relevant. The functions and necessity of the biologically interacting proteins within the mammalian circadian clock will then be determined. Thus, this work will identify novel circadian clock proteins, which may serve as therapeutic targets for ameliorating clock related ailments (e.g. jet lag, shift work) and more serious conditions such as circadian rhythm sleep disorders and other clock-related psychological disorders (e.g. seasonal affective disorder).