Genetic and Genomic Investigations of Fat Storage and Metabolism in C. elegans

线虫脂肪储存和代谢的遗传和基因组研究

基本信息

批准号：
8517101
负责人：
Jennifer L Watts
金额：
$ 29.64万
依托单位：
WASHINGTON STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-02-01 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8517101
关键词：
Adverse effects Affect Animal Model Appetite Regulation Caenorhabditis elegans Cardiovascular Diseases Caring Cell physiology Collection Complex Diabetes Mellitus Employee Strikes Enhancers Epidemic Equilibrium Evolution Fatty acid glycerol esters Funding Gene Expression Gene Targeting Genes Genetic Genetic Epistasis Genetic Screening Genomics Goals Grant Growth Health Healthcare Systems Homeostasis Human Hypertension Incidence Insulin Insulin Signaling Pathway Investigation Laboratories Lead Lipids Longevity Malignant Neoplasms Metabolic Metabolic Control Metabolism Molecular Mutation Nodal Non-Insulin-Dependent Diabetes Mellitus Nuclear Receptors Obesity Organism Pathway interactions Peptide Signal Sequences Pharmacologic Substance Proteins RNA Interference Receptor Signaling Regulation Regulator Genes Regulatory Pathway Reproduction Research Research Training Resistance Resources Role Signal Pathway Signal Transduction Signal Transduction Pathway Sirolimus Study models Techniques Weight Gain Work World Health combat desaturase design detection of nutrient fatty acid metabolism innovation insight insulin signaling interest lipid metabolism mutant novel obesity treatment oxidation public health relevance research study response

项目摘要

DESCRIPTION (provided by applicant): Genetic and genomic investigations of fat storage and metabolism in C. elegans. Obesity afflicts millions of world citizens. The health problems associated with obesity are rising at epidemic rates, challenging world health care systems to provide adequate care. The long-term goal of this research is to dissect the pathways of fat regulation to better understand the mechanisms by which specific genes act to either promote or facilitate resistance to obesity. Our work in the model organism Caenorhabditis elegans has led the identification of conserved regulators of lipid homeostasis. The central hypothesis underlying these studies is that changes in fat stores occur as a result of interactions between regulatory pathways and downstream lipid metabolism genes. This grant proposes to identify fat-regulatory and fat-modulating genes downstream of the key transcriptional regulators NHR-64 and DAF-16/FoxO. The identification of lipid regulators, their functional roles, and their place in the genetic regulatory hierarchy will be explored by means of gene expression studies, genetic epistasis analysis, functional studies using RNA interference, and lipid analysis. An extensive collection of mutants, together with the powerful genetic and genomic resources available in C. elegans, will allow rapid functional assessment of molecules regulating fat storage and lead to a better understanding of their interactions with other fat regulatory pathways. PUBLIC HEALTH RELEVANCE: Studies of fat storage regulation in C. elegans will identify key target genes that modulate fat storage in response to conserved transcriptional regulators and signal transduction pathways. New insights into the mechanisms controlling fat storage will contribute to a broader understanding of the causes and potential treatments of obesity and diabetes.

描述（由申请人提供）：秀丽隐杆线虫中脂肪储存和代谢的遗传和基因组研究。肥胖症困扰着数百万的世界公民。与肥胖相关的健康问题正在以流行病的速度增加，挑战了世界医疗保健系统以提供足够的护理。这项研究的长期目标是剖析调节脂肪调节的途径，以更好地了解特定基因促进或促进对肥胖的抗性的机制。我们在模型生物秀丽隐杆线虫中的工作已导致鉴定脂质体内稳定的调节剂。这些研究的基础假设是，由于调节途径与下游脂质代谢基因之间的相互作用，脂肪存储的变化发生。该赠款建议确定关键转录调节器NHR-64和DAF-16/FOXO下游的脂肪调节和脂肪调节基因。脂质调节剂，其功能作用及其在遗传调节层次结构中的位置将通过基因表达研究，遗传性上学分析，使用RNA干扰的功能研究以及脂质分析来探索。大量的突变体以及秀丽隐杆线虫中可用的强大遗传和基因组资源的集合将允许对调节脂肪储存的分子进行快速的功能评估，并可以更好地理解其与其他脂肪调节途径的相互作用。公共卫生相关性：秀丽隐杆线虫中对脂肪储存调节的研究将确定关键的靶基因，这些基因可根据保守的转录调节剂和信号转导途径调节脂肪储存。对控制脂肪存储的机制的新见解将有助于更广泛地了解肥胖和糖尿病的原因和潜在治疗方法。