Gene regulatory and metabolic network structure, function and evolution

项目总结 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，也是两者的核心 可能会在众多人类疾病中出差错。代谢变化影响基因表达和 反过来说。而新陈代谢和基因表达之间的相互作用已经在 在单个基因和途径中，许多问题仍然没有被探索，特别是在系统中， 或网络，层级。这一提议背后的核心问题是：如何、在哪里以及为什么 转录控制新陈代谢，反之亦然？有关以下几个关键问题和挑战 对于这一首要问题，将使用线虫作为整个动物来解决 模型系统。我们将利用基因筛查、基因表达谱和代谢组学来 以不同级别的解决方案回答关键问题：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、系统级别的以及深层次的 基因表达代谢调控和转录调控的机械论观点 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.