Genetic analysis of mitochondrial regulators in mammalian cells

哺乳动物细胞线粒体调节因子的遗传分析

基本信息

批准号：
8101895
负责人：
JOHN C YOON
金额：
$ 16.02万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-15 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8101895
关键词：
Advisory Committees Affect Animal Model Biochemical Biochemical Genetics Biogenesis Bioinformatics Biological Biological Assay Biology Cell Line Cells Clinical Complement Congenital Abnormality Dana-Farber Cancer Institute Data Degenerative Disorder Development Diabetes Mellitus Disease Doctor of Philosophy Endocrinology Energy Metabolism Environment Exercise Gene Expression Gene Expression Profiling Gene Silencing Gene Targeting General Hospitals Generations Genes Genetic Genetic Screening Genome Genomic Library Genomics Human Individual Insulin Resistance Investigation Laboratories Language Link Mammalian Cell Massachusetts Membrane Potentials Metabolic Diseases Metabolism Methods Mitochondria Molecular Morphology Mus Muscle Muscle Cells Muscle Fibers Mutation Non-Insulin-Dependent Diabetes Mellitus Nuclear Obesity Oxygen Consumption Pathology Phenotype Physicians Physiological Physiology Pilot Projects Play Process Production Protein Binding Proteins Public Health RNA Interference Regulation Regulatory Pathway Reporter Genes Research Research Personnel Resources Respiration Role Scientist Screening procedure Signal Pathway Skeletal Muscle Small Interfering RNA Structure Syndrome Technical Expertise Techniques Testing Training Transcriptional Activation Transfection Zinc Fingers base career career development density experience gene repression genetic analysis glucose metabolism high throughput screening in vivo innovation insight lipid metabolism loss of function medical schools mitochondrial dysfunction mitochondrial membrane mouse genome overexpression professor programs promoter protein expression research study scale up tool

项目摘要

DESCRIPTION (provided by applicant): This application describes a five-year research career development program in the study of mechanisms of mitochondrial proliferation and function in mammalian cells. The research program will be carried out in the laboratory of Dr. Stephen Elledge, Professor of Genetics at Harvard Medical School. Dr. Elledge has successfully trained many academic scientists in the past. The candidate is a clinical fellow in Endocrinology, Diabetes, and Metabolism at Massachusetts General Hospital, and previously carried out Ph.D. research on glucose and lipid metabolism with Dr. Bruce Spiegelman at Dana-Farber Cancer Institute. The proposed research program will provide training in genetic approaches to analyzing regulatory pathways in mammalian cells, including gene silencing by RNA interference. The candidate will also acquire expertise in a number of genomics and bioinformatics methods. These experiences will complement the candidate's previous training in metabolism and will aid his development as an independent physician-scientist. To further enhance the training, an advisory committee of experts in mitochondrial biology, metabolism and molecular physiology, and mouse genetics will provide scientific and career advice. In a pilot study utilizing an RNAi-based genetic screen, the candidate has identified a zinc finger protein as a regulator of mitochondrial biogenesis and function in mammalian skeletal muscle cells. Preliminary evidence suggests that this protein is regulated in physiological contexts. The candidate intends to carry out further characterization of the effect of the protein on muscle cell mitochondrial number and activity. The molecular mechanism underlying the protein's effect will be investigated using a combination of biochemical, genetic, and cell biological approaches. In parallel, an expanded RNAi screen encompassing the entire genome will be carried out to obtain a global view of the regulatory pathways with particular emphasis on transcriptional networks. The Elledge lab provides a stimulating intellectual environment, broad technical expertise, and extensive scientific resources that reflect years of continuous innovation in the lab. It is an ideal setting for the candidate to develop professionally and to successfully launch his academic career as a physician-scientist. Relevance to public health (lay language): We aim to study the genes involved in mitochondrial proliferation and function. These studies may eventually help understand and treat diseases, such as type 2 diabetes, which are known to be characterized by abnormalities in mitochondrial number and function.

描述（由申请人提供）：该应用描述了一项为期五年的研究职业发展计划，用于研究哺乳动物细胞中线粒体增殖和功能的机制。该研究计划将在哈佛医学院遗传学教授Stephen Elledge博士的实验室进行。过去，Eledge博士过去曾成功培训了许多学术科学家。该候选人是马萨诸塞州综合医院的内分泌，糖尿病和代谢的临床研究员，此前曾获得博士学位。 Dana-Farber癌症研究所的Bruce Spiegelman博士对葡萄糖和脂质代谢的研究。拟议的研究计划将提供有关分析哺乳动物细胞调节途径的遗传方法的培训，包括通过RNA干扰进行基因沉默。候选人还将获得许多基因组学和生物信息学方法的专业知识。这些经历将补充候选人以前在代谢方面的培训，并将帮助他作为独立医师科学家的发展。为了进一步增强培训，线粒体生物学，代谢和分子生理学专家咨询委员会以及老鼠遗传学将提供科学和职业建议。在利用基于RNAi的遗传筛查的试点研究中，候选者已将锌指蛋白确定为哺乳动物骨骼肌细胞中线粒体生物发生和功能的调节剂。初步证据表明，该蛋白在生理环境中受到调节。候选人打算进一步表征蛋白质对肌肉细胞线粒体数和活性的影响。将使用生化，遗传和细胞生物学方法的组合研究蛋白质作用的分子机制。同时，将进行包含整个基因组的扩展的RNAi屏幕，以获得调节途径的全局视图，并特别强调转录网络。 Eledge实验室提供了一个令人兴奋的智力环境，广泛的技术专长和广泛的科学资源，反映了实验室中连续创新的多年。这是候选人专业发展并成功启动他作为医师科学家的学术生涯的理想场所。与公共卫生（外行语言）相关：我们旨在研究与线粒体增殖和功能有关的基因。这些研究最终可能有助于理解和治疗疾病，例如2型糖尿病，已知这些疾病的特征是线粒体数和功能的异常。