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。我们研究两种生物学 网络及其之间的交互。首先，我们表征了物理和功能基因 在发育和增长过程中是基因转录的主要控制器的监管网络， 维持体内平衡并应对环境线索和侮辱。我们将扩大我们的 秀丽隐杆线虫中基因启动子和转录因子之间的物理相互作用的研究 关注体内真正功能性，组织特异性的调节网络。这将涉及考试 间接影响转录的非转录因子调节剂的。第二，我们研究代谢 将养分转化为生物质和能量的网络。我们将执行实验以获得洞察力 进入不同组织和不同营养条​​件下的代谢网络如何连接。在 此外，我们将继续开发我们的Wormflux网站以启用数据集成和通量 与选定参数（例如生物质组成和不同目标）的平衡分析 功能。最后，重要的是，我们研究基因调节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中扰动的影响 基因。此外，我们将在不同条件下生成基因表达数据，以检查 基因表达变化会影响代谢。我们的数据将提供广泛的现象学和 深厚的机械见解以及大型社区的一组资源。