RESCUING MOTOR DEFICITS IN SHANK3 RELEATED DISORDERS

 描述(由申请人提供)：这份建议书描述了一项为期五年的职业发展培训计划，旨在引导您在翻译神经科学领域取得独立的学术生涯。申请人：申请人拥有医学博士学位，并已完成儿科和儿童神经科的专业培训。他之前在人类遗传学研究和开发神经疾病的小鼠模型方面有经验。职业发展计划包括一段时间的指导研究，旨在发展基本的神经科学知识和技术，这将极大地增强他以前的训练，并使他能够发展独立。培训将包括学习研究技术和概念，并辅之以教学培训、研讨会、实验室会议、期刊俱乐部、全国会议、咨询委员会和与导师的会议。研究环境提供了最好的智力环境和可用的最好的技术，并使申请者有机会在学习强大的实验室技术方面得到指导。除了培养实验室技能外，职业发展计划还包括授课培训、拨款撰写和负责任的研究行为。研究计划：突触后蛋白编码基因Shanks的功能障碍是一个新的、不断增长的科学兴趣领域。SHANK3基因缺失会导致Phelan-Mcdermid综合征(PMS)，这是一种自闭症谱系障碍。他最近确定，人类的复制和小鼠的过度表达也会导致神经发育症状。在这项提案中，申请人旨在通过遗传和化学遗传学方法逆转这些小鼠的运动表型，研究导致Shank3过表达表型的神经元和分子机制。他使用无偏见的蛋白质组学方法研究了驱动过度表达表型的分子机制，并确定了Shank3和多巴胺受体信号之间的新联系。

 DESCRIPTION (provided by applicant): This proposal describes a five-year career development training program designed to lead to an independent academic career in translational neuroscience. Applicant: The applicant holds an M.D. and Ph.D. degree, and has completed specialty training in both Pediatrics and Child Neurology. He has previous experience with human genetics research and developing mouse models of neurologic disease. The career development plan includes a period of mentored research aimed at developing basic neuroscience knowledge and techniques that will greatly enhance his previous training and allow him to develop independence. The training will include learning research techniques and concepts supplemented by didactic training, seminars, lab meetings, journal clubs, national meetings, an advisory committee and meetings with the mentor. The research environment provides the best intellectual environment and the best technology available and gives the applicant the opportunity to be guided in learning powerful laboratory techniques. In addition to developing laboratory skills, the career development plan includes didactic training in grant writing and responsible conduct in research. Research plan: Disorders of function of the post-synaptic protein encoding gene called SHANKs are a new and growing area of scientific interest. Deficiency of SHANK3 causes Phelan-McDermid Syndrome (PMS) which is an autism spectrum disorder. He recently determined that duplications in humans and overexpression in mice also leads to neurodevelopmental symptoms. In this proposal, the applicant aims to investigate the neuronal and molecular mechanisms contributing to the Shank3 overexpression phenotype by genetic and chemo genetic methods to reverse the motor phenotype of these mice. He has used unbiased proteomic approach to investigate the molecular mechanisms driving the overexpression phenotype and identified a novel connection between Shank3 and dopamine receptor signaling.