INSULIN STIMULATION OF GLUCOSE TRANSPORTER TRANSLOCATION

申请人提出一个多方面的培训计划，将准备 他在内分泌和代谢生物学的基础研究生涯 系统. 该计划将包括正式的教学经验， 哈佛大学、哈佛医学院的研究生课程， 马萨诸塞州理工学院在分子和 细胞生物学、病毒学、免疫学和遗传学。 申请人将 利用上述机构主办的许多讲座和研讨会， 机构，以及马萨诸塞州总医院和 怀特黑德生物医学研究所。 第一阶段的核心经验将是进行一个研究项目， Harvey F博士的实验室。Lodish，怀特黑德研究所成员 麻省理工学院的生物学教授 在申请人过去的实验室 接受梅森·弗里曼医学博士的训练他对泡状的 转运和膜靶向。 Lodish博士分享了这种兴趣， 在这方面有丰富的经验 申请人的总体目标 他的研究计划是剖析信号传导途径。之间 胰岛素受体和葡萄糖转运蛋白。 小gtp结合 RAB家族的蛋白质已经牵涉到 囊泡运输 第一阶段的具体目标是测试 假设一种特异性小GTP结合蛋白Rab3D， 最近在洛迪什博士的实验室被克隆， 这个信号转导途径。 其他具体目标将是 研究Rab3D的生物化学，并鉴定和克隆其他 在胰岛素反应细胞中调节葡萄糖转运的蛋白质。 研究计划的成功完成有望产生重要的成果。 深入了解胰岛素抵抗综合征， 糖尿病的 申请人在第一阶段的进展将是 由任命的科学家和医生组成的咨询委员会进行监测， 罗迪什博士和约翰·T.小波茨，医务处处长 在马萨诸塞州总医院 对于第二阶段，申请人将返回MGH并继续这一行， 研究与他的第二阶段赞助商，约瑟夫Avruch博士， 他对胰岛素受体信号转导有着长期的兴趣。 概括地说，申请人将研究调节蛋白 在胰岛素抵抗动物模型和人类中的I期期间克隆 糖尿病的 第二阶段的具体建议如下： 在第一阶段进行的实验中发展出来的。

The applicant proposes a multifaceted training program that will prepare him for a basic research career in the biology of endocrine and metabolic systems. This program will include formal didactic experience in graduate level courses at Harvard University, Harvard Medical School, and the Massachusetts Institute of Technology in the fields of molecular and cellular biology, virology, immunology, and genetics. The applicant will take advantage of numerous lectures and seminars sponsored by the above institutions, as well as by Massachusetts General Hospital and the Whitehead Institute for Biomedical Research. The core experience of Phase I will be to conduct a research project in the laboratory of Dr. Harvey F. Lodish, Member of the Whitehead Institute and Professor of Biology at MIT. During the applicant's past laboratory training with Mason Freeman, M.D., he developed an interest in vesicular transport and membrane targeting. Dr. Lodish shares this interest and has considerable experience in the field. The applicant's broad goal in his research plan is to dissect the signal transduction pathway. between the insulin receptor and glucose transporters. Small GTP-binding proteins of the rab family have been implicated in the regulation of vesicular transport. The specific aims of Phase I will be to test the hypothesis that a specific small GTP-binding protein, Rab3D, which recently has been cloned in Dr. Lodish's laboratory, participates in this signal transduction pathway. Other specific aims will be to investigate the biochemistry of Rab3D and to identify and clone other proteins that regulate glucose transport in insulin-responsive cells. Successful completion of the research plan promises to yield important insights into the syndromes of insulin resistance that characterize diabetes mellitus. The applicant's progress through Phase I will be monitored by an advisory committee of scientists and physicians appointed by Dr. Lodish and Dr. John T. Potts, Jr., the Chief of Medical Services at Massachusetts General Hospital. For Phase II the applicant will return to MGH and continue this line of research in collaboration with his Phase II sponsor, Dr. Joseph Avruch, who has a longstanding interest in insulin receptor signal transduction. Broadly stated, the applicant will investigate the regulatory proteins cloned during Phase I in animal models of insulin resistance and in human diabetes mellitus. More specific proposals for Phase II will be developed out of the experiments performed during Phase I.