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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）：