Gene regulatory and metabolic network structure, function and evolution

项目摘要 代谢和基因表达是大多数生物过程的核心， 会在很多人类疾病中出错。代谢变化影响基因表达， 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， 个别基因和途径，许多问题仍然没有探索，特别是在系统， 或网络级。这一建议的核心问题是：如何、在何处和为什么 转录控制代谢，反之亦然？有关的几个关键问题和挑战 将使用线虫C.作为一个整体的动物 模型系统我们将采用基因筛选、基因表达谱分析和代谢组学， 回答不同层次的关键问题：从网络层次，到路径层次， 电路/分子水平。这使我们能够获得广泛的，系统级的以及深入的 对基因表达的代谢控制和转录控制的机制的见解 新陈代谢的过程。

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.