Gene Regulatory Networks in Development and Physiology

发育和生理学中的基因调控网络

基本信息

批准号：
8814454
负责人：
A. J. Marian Walhout
金额：
$ 63.87万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-05-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8814454
关键词：
Address Affect Aging Animal Feed Animals Bacteria Biochemical Pathway Biological Assay Biomedical Research Branched-Chain Amino Acids Butyryl-CoA dehydrogenase Caenorhabditis elegans Chromosome Mapping Citric Acid Cycle Collection Comamonas Cues Development Diabetes Mellitus Diet Dietary Fiber Disease Eating Endocrine system Escherichia coli Essential Amino Acids Fertility Fertility Rates Gene Expression Genes Genetic Genetic Screening Genetic Transcription Genomics Goals Green Fluorescent Proteins Health Human Inborn Errors of Metabolism Individual Intestines Laboratories Lead Life Link Longevity Maps Measures Mediating Mediator of activation protein Metabolic Metabolism Methionine Micronutrients Modeling Mutation Nematoda Nutrient Nutritional Nutritional Requirements Obesity Output Pathway interactions Phenotype Physiological Physiology Propionic Acids RNA Interference Regulator Genes Relative (related person)Resources Soil Supplementation System Systems Biology Testing Toxic effect Transgenic Organisms Translating Uncertainty Vitamin B 12 Vitamins Volatile Fatty Acids bacterial genetics gastrointestinal system glycine cleavage system innovation insight ketotic hyperglycinemia mutant offspring promoter public health relevance response trait transcription factor transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): What we eat greatly influences how we function and affects our propensity to get diseases such as obesity and diabetes. A major goal of Biomedical Research is to uncover which nutrients and metabolites affect our physiology on the one hand and, which of our genes mediate the physiological response to these molecules on the other. We have recently developed an innovative interspecies systems biology model of the nematode C. elegans and its bacterial diet to address these questions. We have used this model to uncover bacterially derived micronutrients and metabolites that affect gene expression, development and fertility in the worm, and to identify a C. elegans metabolic regulatory network that mediates the response to bacterial nutrients. The effects of different bacteria (and their molecules) are mediated via the animal's intestine, which functions as both a digestive and endocrine system. In the next project we will more precisely define the genes that are affected by different bacterial diets, as well as by vitamin B12 and propionic acid - molecules that are central mediators of the effects we observed. In addition, we will use systems-level phenotypic assays and genetic interaction screens to link diet-induced gene expression changes to physiological outputs such as altered developmental rate, fertility, and lifespan and the ability t response to propionic acid toxicity. Finally, we will dissect the precise mechanisms by which metabolic networks communicate with gene regulatory networks and vice versa using a set of transcription factors that are involved in mediating the response to nutritional cues.

描述（由申请人提供）：我们吃的东西极大地影响我们的机能，并影响我们患肥胖症和糖尿病等疾病的倾向。生物医学研究的一个主要目标是一方面揭示哪些营养物质和代谢物影响我们的生理机能，另一方面我们的哪些基因介导对这些分子的生理反应。我们最近开发了一种创新的线虫种间系统生物学模型。线虫及其细菌饮食来解决这些问题。我们利用这个模型来揭示影响线虫基因表达、发育和生育力的细菌来源的微量营养素和代谢物，并确定了介导对细菌营养素反应的线虫代谢调节网络。不同细菌（及其分子）的作用是通过动物肠道介导的，动物肠道既具有消化系统又具有内分泌系统的功能。在下一个项目中，我们将更精确地定义受不同细菌饮食以及维生素 B12 和丙酸分子影响的基因，这些分子是我们观察到的影响的核心介质。此外，我们将使用系统级表型测定和遗传相互作用筛选，将饮食诱导的基因表达变化与生理输出联系起来，例如发育速度、生育力和寿命的改变以及对丙酸毒性的反应能力。最后，我们将使用一组参与介导对营养线索的反应的转录因子来剖析代谢网络与基因调控网络通信的精确机制，反之亦然。