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: 9918415
• 负责人: A. J. Marian Walhout
• 金额: $ 81.93万
• 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 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9918415
• 关键词: Affect; Biochemical Pathway; Biological; Biological Process; Biomass; Caenorhabditis elegans; Communities; Congenital Disorders; Cues; Data; Disease; Equilibrium; Evolution; Gene Expression; Gene Expression Regulation; Genes; Genetic Transcription; Growth and Development function; Homeostasis; Inborn Errors of Metabolism; Intestines; Malignant Neoplasms; Metabolic; Metabolism; Nutrient; Nutritional; Regulator Genes; Resources; Structure; Testing; Tissues; data integration; driving force; experimental study; in vivo; insight; metabolic abnormality assessment; promoter; transcription factor; web site

Biological networks describe relationships between biomolecules. We study two types of biological networks and the interactions between them. First, we characterize physical and functional gene regulatory networks that are primary controllers of gene transcription during development and growth, to maintain homeostasis and to respond to environmental cues and insults. We will expand our studies on physical interactions between gene promoters and transcription factors in C. elegans to focus on true functional, tissue-specific regulatory networks in vivo. This will involve the examination of non-transcription factor regulators that affect transcription indirectly. Second, we study metabolic networks that convert nutrients into biomass and energy. We will perform experiments to gain insight into how metabolic networks are wired in different tissues and under different nutritional conditions. In addition, we will continue to develop our WormFlux website to enable data integration and flux balance analysis with selected parameters such as biomass composition and different objective functions. Finally, and importantly, we study how gene regulatory networks affect metabolic networks and vice versa. We will test how intestinal transcription is affected by perturbations in metabolic genes. In addition, we will generate gene expression data under different conditions to examine how gene expression changes influence metabolism. Our data will provide broad phenomenological and deep mechanistic insights, as well as a set of resources for the larger community.

生物网络描述了生物分子之间的关系。我们研究两种类型的生物 网络以及它们之间的相互作用。首先，我们表征物理和功能基因 调控网络是发育和生长过程中基因转录的主要控制者， 维持体内平衡并对环境暗示和侮辱做出反应。我们将扩大我们的 线虫基因启动子和转录因子之间物理相互作用的研究 专注于体内真正功能性的、组织特异性的调控网络。这会涉及到考试 间接影响转录的非转录因子调节因子。其次，我们研究新陈代谢 将营养物质转化为生物质和能量的网络。我们将进行实验以获得洞察力 研究代谢网络如何在不同组织和不同营养条​​件下连接。在 此外，我们将继续开发 WormFlux 网站，以实现数据集成和通量 使用选定参数（例如生物量组成和不同目标）进行平衡分析 功能。最后，也是重要的，我们研究基因调控网络如何影响代谢网络 反之亦然。我们将测试肠道转录如何受到代谢扰动的影响 基因。此外，我们将生成不同条件下的基因表达数据，以检验如何 基因表达的变化影响新陈代谢。我们的数据将提供广泛的现象学和 深刻的机制见解，以及为更大的社区提供的一组资源。