Functional Analysis of PGC1-a holo-complex in Diabetes

描述(由申请人提供)： 这项建议详细说明了一个为期5年的培训计划，旨在为首席研究人员在学术医学领域的职业生涯做好准备。首席研究员满足了约翰霍普金斯医院的内科临床要求和布里格姆妇女医院的心脏病学奖学金。该计划鼓励获得合理的原则和专业知识，以研究转录共激活因子，PPAR伽马共激活因子1α(PGC1-α)，因为它与新陈代谢有关。布鲁斯·M·斯皮格尔曼博士是能量代谢领域的先驱，他将通过提供职业和科学指导来指导首席研究员。 这项研究致力于阐明PGC1-α全息复合体在糖尿病和能量代谢中的作用。实验室以前的遗传学研究发现了几个受PGC1-α调控的转录因子，并强调了PGC1-α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-α全息复合体的特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)建立一种通用的分离PGC1-α全息复合体的技术。2)阐明正常组织和糖尿病组织中组成PGC1-α全息复合体的蛋白质。3)研究PGC1-α复合体的分子生物学意义。这项研究首次对前列腺素C_1-α全息复合体进行了功能和蛋白质组学分析，并可能定义前列腺素C_1-α在糖尿病中的新调节作用。 达纳-法伯癌症研究所的癌症生物学系提供了一个富有启发性和科学依据的基础，首席研究人员可以在此基础上在学术医学领域建立自己的事业。最终，环境和项目将促进首席研究员发展成为一名独立的内科科学家。

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.