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。我们研究了两种生物 网络以及它们之间的相互作用。首先，我们描述了物理和功能基因 调控网络是发育和生长过程中基因转录的主要控制者， 以维持体内平衡并对环境线索和侮辱做出反应。我们将扩大我们 研究了C.优雅地 专注于真正的功能性，组织特异性调节网络在体内。这将涉及检查 间接影响转录的非转录因子调节子。第二，我们研究代谢 将养分转化为生物质和能量的网络。我们将通过实验来了解 代谢网络在不同组织和不同营养条件下是如何连接的。在 此外，我们将继续开发我们的WormFlux网站，以实现数据集成和流量 平衡分析与选定的参数，如生物量组成和不同的目标 功能协调发展的最后，也是重要的，我们研究基因调控网络如何影响代谢网络 且反之亦然。我们将测试肠道转录如何受到代谢紊乱的影响， 基因.此外，我们将在不同条件下生成基因表达数据，以研究如何 基因表达变化影响代谢。我们的数据将提供广泛的现象学和 深刻的机械见解，以及一套资源，为更大的社区。