Functional Analysis of PGC1-a holo-complex in Diabetes

描述（由申请人提供）： 该提案详细介绍了一个为期5年的培训计划，旨在为主要研究者在学术医学领域的职业生涯做好准备。主要研究者符合约翰霍普金斯医院内科和布里格姆妇女医院心脏病学研究员的临床要求。该计划鼓励获得良好的原则和专业知识，用于研究转录共激活因子，PPAR γ共激活因子1 α（PGC 1-alpha），因为它涉及代谢。布鲁斯M. Spiegelman博士是能量代谢领域的先驱，将通过提供职业和科学指导来指导首席研究员。 该研究致力于阐明PGC 1-alpha全息复合物在糖尿病和能量代谢中的作用。实验室先前的遗传研究确定了几种受PGC 1- alpha调节的转录因子，并强调了PGC 1-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PGC 1-alpha全复合物的表征将识别调节糖尿病和能量代谢的新因素。该项目的具体目标是：1）建立一种分离PGC 1-α全复合物的通用技术。2)从正常和糖尿病组织中阐明包含PGC 1-α全复合物的蛋白质。3)描述PGC 1-α复合物的分子和生物学意义。这项研究构成了PGC 1-alpha全复合物的第一个功能和蛋白质组学分析，并可能定义PGC 1-alpha在糖尿病中的新调控作用。 丹娜-法伯癌症研究所的癌症生物学系提供了一个刺激和科学合理的基础，首席研究员可以在学术医学领域建立职业生涯。最终，环境和计划将促进主要研究者发展成为独立的医生科学家。

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.