Functional Analysis of PGC1-a holo-complex in Diabetes

PGC1-a 全复合物在糖尿病中的功能分析

基本信息

批准号：
7599244
负责人：
Marcus P Cooper
金额：
$ 13.15万
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 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7599244
关键词：
Animals Binding Biochemical Biogenesis Biological Biological Assay Cancer Biology Cardiology Cell Culture Techniques Cell Line Cell physiology Cells Chromatography Clinical Complex Dana-Farber Cancer Institute Development Diabetes Mellitus Doctor of Medicine Doctor of Philosophy Energy Metabolism Environment Epitopes Exhibits Fasting Fatty Acids Fellowship Fostering Genetic Genetic Transcription Heart Hela Cells Homeostasis Hospitals Internal Medicine Investigation Laboratories Liver Medicine Mentors Metabolism Mitochondria Molecular Mus Muscle Non-Insulin-Dependent Diabetes Mellitus Nuclear Extract PPAR gamma Phenotype Physicians Physiology Play Principal Investigator Proteins Proteome Proteomics Research Research Personnel Role Scientist Skeletal Muscle Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Sum Techniques Therapeutic Tissues Training Programs Woman base career design diabetic established cell line gain of function insight interest loss of function member novel novel diagnostics programs protein complex sound tool transcription factor

项目摘要

DESCRIPTION (provided by applicant): This proposal details a 5-year training program and is designed to prepare the principal investigator for a career in academic medicine. The principal investigator has fulfilled clinical requirements for internal medicine at the Johns Hopkins Hospital and cardiology fellowship at Brigham and Women's Hospital. The program encourages the acquisition of sound principles and expertise for studying the transcriptional co-activator, PPAR gamma co-activator 1 alpha (PGC1-alpha), as it pertains to metabolism. Bruce M. Spiegelman, Ph.D. is a pioneer in the field of energy metabolism and will mentor the principal investigator by providing career and scientific guidance. The research endeavors to elucidate the role of the PGC1-alpha holo-complex in diabetes and energy metabolism. Prior genetic studies in the laboratory identified several transcription factors regulated by PGC1- alpha and highlighted the pivotal role of PGC1-alpha in energy homeostasis. The proteome is the final determinant of cellular phenotype, and we hypothesize that characterization of the PGC1-alpha holo-complex will identify novel factors that regulate diabetes and energy metabolism. Specific aims of the project are: 1) Establish a versatile technique to isolate PGC1-alpha holo-complexes. 2) Elucidate the proteins comprising the PGC1-alpha holo-complex from normal and diabetic tissues. 3) Characterize the molecular and biological significance of the PGC1-alpha complex. This study constitutes the first functional and proteomic analysis of the PGC1-alpha holo-complex, and may define new regulatory roles for PGC1-alpha in diabetes. The department of Cancer Biology at the Dana-Farber Cancer Institute provides a stimulating and scientifically sound base from which the principal investigator can build a career in academic medicine. Ultimately, the environment and the program will foster the development of the principal investigator into an independent physician-scientist.

描述（由申请人提供）：该建议详细介绍了一项为期5年的培训计划，旨在为主要研究人员准备学术医学职业。首席研究人员在Brigham和妇女医院的Johns Hopkins医院和心脏病学研究金已经满足了内科的临床要求。该计划鼓励获得声音原理和专业知识，以研究转录共激活因子PPAR GAMMA共激活器1 alpha（PGC1-Alpha），因为它与代谢有关。 Bruce M. Spiegelman博士是能源代谢领域的先驱，并将通过提供职业和科学指导来指导主要研究者。这项研究旨在阐明PGC1-Alpha Holo-复合物在糖尿病和能量代谢中的作用。实验室的先前遗传研究确定了由PGC1-Alpha调节的几种转录因子，并强调了PGC1-Alpha在能量稳态中的关键作用。蛋白质组是细胞表型的最终决定因素，我们假设PGC1-Alpha Holo-complex的表征将确定调节糖尿病和能量代谢的新因素。该项目的具体目的是：1）建立一种多功能技术来隔离PGC1-Alpha Holo-complexes。 2）阐明来自正常和糖尿病组织的PGC1-Alpha Holo-复合物的蛋白质。 3）表征PGC1-Alpha复合物的分子和生物学意义。这项研究构成了PGC1-Alpha Holo-Complex的首次功能和蛋白质组学分析，并且可能定义了PGC1-Alpha在糖尿病中的新调节作用。 Dana-Farber癌症研究所的癌症生物学系提供了一个令人兴奋且科学的基础，主要研究人员可以从中建立学术医学职业。最终，环境和计划将促进主要研究人员发展为独立医师科学家。