Gene regulatory and metabolic network structure, function and evolution

项目概要 新陈代谢和基因表达是大多数（如果不是全部）生物过程的核心 可能会导致多种人类疾病。代谢变化影响基因表达，反之亦然 反之亦然。虽然代谢和基因表达之间的相互作用已经在水平上进行了研究 关于个体基因和途径，许多问题仍有待探索，特别是在系统方面， 或网络、级别。该提案的核心问题是：如何、在何处以及为何 转录控制代谢，反之亦然？相关的几个关键问题和挑战 这个首要问题将使用线虫秀丽隐杆线虫作为一个整体动物来解决 模型系统。我们将采用遗传筛选、基因表达谱和代谢组学来 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、系统级的和深入的 对基因表达代谢控制和转录控制的机制见解 的新陈代谢。

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.