Gene regulatory and metabolic network structure, function and evolution

基因调控和代谢网络的结构、功能和进化

• 批准号: 10409002
• 负责人: A. J. Marian Walhout
• 金额: $ 84.39万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10409002
• 关键词: Address; Affect; Animal Model; Automobile Driving; Biochemical Pathway; Biological Models; Biological Process; Caenorhabditis elegans; Evolution; Gene Expression; Gene Expression Profiling; Gene Expression Regulation; Genes; Genetic Screening; Health; Heart; Individual; Metabolic; Metabolic Control; Metabolism; Molecular; Nematoda; Pathway interactions; Process; Regulator Genes; Resolution; Structure; System; Transcriptional Regulation; human disease; insight; metabolomics

PROJECT SUMMARY Metabolism and gene expression lie at the heart of most, if not all, biological processes and both can go awry in a plethora of human diseases. Metabolic changes affect gene expression and vice versa. While the interplay between metabolism and gene expression has been studied at the level of individual genes and pathways, many questions remain unexplored, especially at the systems, or network, level. The central question underlying this proposal is: How, where and why does transcription control metabolism and vice versa? Several key questions and challenges pertaining to this overarching question will be addressed using the nematode C. elegans as a whole animal model system. We will employ genetic screens, gene expression profiling and metabolomics to answer key questions at different levels of resolution: from the network level, to the pathway level, the circuitry/molecular level. This enables us gain both broad, systems-level as well as deep mechanistic insights into the metabolic control of gene expression and the transcriptional control of metabolism.

项目摘要 代谢和基因表达是大多数（如果不是全部）生物学过程的核心，既是 在大量的人类疾病中可能会出现问题。代谢变化会影响基因表达和恶化 Versa。虽然已经研究了新陈代谢和基因表达之间的相互作用。 在单个基因和途径中，许多问题仍未探索，尤其是在系统中， 或网络，级别。该提案的基础问题是：如何，何处，为什么 转录控制代谢，反之亦然？关于有关的几个关键问题和挑战 对于整个动物，将使用线虫C.秀丽隐杆线虫来解决这个总体问题 模型系统。我们将采用遗传筛选，基因表达分析和代谢组学 回答不同分辨率级别的关键问题：从网络级别到路径级别， 电路/分子水平。这使我们能够获得广泛的，系统级别和深度 对基因表达的代谢控制和转录控制的机械洞察力 代谢。