Postdoctoral Program in Functional Neurogenomics

描述(申请人提供)：神经科学家和内科医生继续努力了解精神疾病背后的病理生理机制，更重要的是将这些信息转化为疾病所需的个性化治疗。尽管过去50年的研究已经发现了支持大脑紊乱的基因、基因变异、分子网络、细胞相互作用和大脑通路，但我们对这些信息的翻译仍然有限。新一代神经科学家需要了解并能够利用1)体内遗传和表观遗传变异的功能影响，2)基因在突触生理中产生变化的发育和调节背景，3)导致行为变化的电路水平的病理，以及4)将研究成果转化为新疗法的最佳实践。我们建议范德比尔特功能神经基因组学博士后培训计划作为一种工具，以确保学科的合并，培训人员在遗传模型系统提供的机会中获得经验，在将人类基因发现转化为构建有效的动物模型方面获得专业知识，学习在体内使用先进的方法操纵分子、细胞和电路，并在捕捉此类操纵的生理和行为后果方面获得经验。我们的项目建立在范德比尔特过去20年在神经科学教师、教育项目、技术专长和核心设施方面的重大投资之上。我们的项目主任是NIMH荣誉奖获得者、范德比尔特·西尔维奥·孔特神经科学研究中心主任兰迪·D·布莱克利博士。布莱克利博士的研究范围从线虫的正向和反向遗传学研究，到在转基因小鼠中建立与精神疾病相关的基因变异的模型，再到识别自闭症和ADHD背后的功能性人类遗传变异。两位长期致力于推动初级科学家事业发展的知名神经学家负责监督该计划。该计划的联合主任是罗杰·D·科恩博士，他是范德比尔特大学分子生理学和生物物理学系主任，也是当选的美国国家科学院院士。科恩博士的研究融合了现代遗传学、分子生物学、生物化学和行为学的工具，重点是中枢神经系统对食欲和饮食障碍的控制。与布莱克利博士类似，科恩博士的研究中使用的范例涵盖了强大的遗传模型系统，包括转基因斑马鱼和小鼠，以探索饮食障碍背后的功能基因变异。像布莱克利博士一样，科恩博士培养了数十名博士后和博士后研究员，为该项目带来了重要的指导经验。

DESCRIPTION (provided by applicant): Neuroscientists and physicians continue to struggle to understand the pathophysiological mechanisms that underlie mental illness, and even more so to translate this information into the personalized therapies needed for diseases. Although research over the past five decades has uncovered genes, gene variants, molecular networks, cellular interactions and brain pathways supporting brain disorders, our translation of this information remains limited. A new generation of neuroscientists is needed that understand, and can exploit, 1) the functional impact of genetic and epigenetic variation in vivo, 2) the developmental and regulatory context within which genes produce alterations in synaptic physiology, 3) the circuit-level pathologies that lead to changes in behavior and 4) the best practices in translating research findings into novel therapies. We propose The Vanderbilt Postdoctoral Training Program in Functional Neurogenomics as a vehicle to insure a merger of disciplines, where trainees gain experience in the opportunities afforded by genetic model systems, gain expertise in the translation of human genetic findings into construct-valid animal models, learn to manipulate molecules, cells and circuits with advanced approaches in vivo, and gain experience in capturing the physiological and behavioral consequences of such manipulations. We build our program on a significant investment over the past two decades by Vanderbilt in neuroscience faculty, educational programs, technological expertise and core facilities. Our Program Director is Randy D. Blakely, Ph.D., an NIMH MERIT awardee and Director of the Vanderbilt Silvio O. Conte Center for Neuroscience Research. Dr. Blakely's research ranges from forward and reverse genetic studies in C. elegans to the modeling of mental illness-associated gene variation in transgenic mice, to the identification of functional human genetic variation underlying autism and ADHD. Two established neuroscientists with a long-standing interest in advancing the careers of junior scientists oversee the Program. The Program Co-Director is Roger D. Cone, Ph.D., Chair of the Department of Molecular Physiology & Biophysics at Vanderbilt, and an elected member of the National Academy of Sciences. Dr. Cone's research incorporates the tools of modern genetics, molecular biology, biochemistry and behavior, with a focus on CNS control of appetite and eating disorders. Similar to Dr. Blakely, the paradigms used in Dr. Cone's research ranges across powerful genetic model systems, including transgenic zebrafish and mice, to research probing for functional gene variation underlying eating disorders. Like Dr. Blakely, Dr. Cone has trained dozens of predoctoral and postdoctoral fellows, bringing significant mentorship experience to the Program.