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：
8930958
负责人：
A. J. Marian Walhout
金额：
$ 59.07万
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/8930958
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 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了我们的运作方式并影响我们获得肥胖和糖尿病等疾病的倾向。生物医学研究的一个主要目标是发现哪些营养素和代谢产物一方面影响我们的生理学，而我们的哪些基因介导了对这些分子的生理反应。我们最近开发了一种创新的种间系统系统生物学模型的线虫C.秀丽隐杆线虫及其细菌饮食，以解决这些问题。我们已经使用该模型来揭示影响蠕虫基因表达，发育和生育能力的细菌衍生的微量营养素和代谢产物，并鉴定了秀丽隐杆线虫的代谢调节网络，该网络介导对细菌营养的反应。不同细菌（及其分子）的作用是通过动物的肠道介导的，该肠既是消化系统又是内分泌系统。在下一个项目中，我们将更精确地定义受不同细菌饮食影响的基因，以及维生素B12和丙酸 - 分子，这些分子是我们观察到的作用的中心介体。此外，我们将使用系统水平的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产量（如发育率改变，生育能力和寿命）以及对丙酸毒性的能力反应。最后，我们将使用一组涉及介导对营养提示的反应的转录因子来剖析代谢网络与基因调节网络进行通信的精确机制。