RESCUING MOTOR DEFICITS IN SHANK3 RELEATED DISORDERS

挽救 3 号小腿相关疾病中的运动缺陷

基本信息

批准号：
9133480
负责人：
JIMMY L HOLDER
金额：
$ 17.82万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9133480
关键词：
Actins Adenylate Cyclase Advisory Committees Area Automobile Driving Bacterial Artificial Chromosomes Behavior Behavioral Biochemistry Bioinformatics Corpus striatum structure Coupled Cytoskeleton Data Development Plans Disease Doctor of Medicine Doctor of Philosophy Dopamine Dopamine Antagonists Dopamine D2 Receptor Dopamine Receptor Embryonic Development Environment Epilepsy Equilibrium Family Future Genes Genetic Genetic Research Genetic study Genetically Engineered Mouse Goals Grant Health Human Human Genetics Hyperactive behavior Individual Intellectual functioning disability Ion Channel Journals Knowledge Laboratories Lead Learning LoxP-flanked allele Mass Spectrum Analysis Membrane Proteins Mentors Methods Modeling Molecular Moods Motor Motor Activity Mus Mutant Strains Mice Mutation Neurodevelopmental Disorder Neurologic Neurons Neurosciences Neurotransmitter Receptor Patient Care Patients Pediatric Neurology Pediatrics Phenotype Population Protein Isoforms Proteins Proteomics Receptor Signaling Research Research Personnel Research Technics Role Seizures Signal Transduction Social Interaction Symptoms Synapses Synaptic plasticity Syndrome Techniques Technology Testing Therapeutic Effect Training Training Programs Transcript Transgenes Work Writing autism spectrum disorder behavior test career career development density design disease-causing mutation experience genetic approach in vivo insight interest loss of function loss of function mutation medical specialties meetings motor deficit motor impairment motor learning mouse model neuronal circuitry neurophysiology novel overexpression postsynaptic repetitive behavior research study response skills synaptic function synaptogenesis tool translational neuroscience

项目摘要

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.

描述（由申请人提供）：该提案描述了一项为期五年的职业发展培训计划，旨在实现转化神经科学领域的独立学术生涯。申请人：申请人拥有医学博士和博士学位，并已完成以下领域的专业培训。他拥有儿科和儿童神经病学方面的经验，并且拥有人类遗传学研究和开发神经系统疾病小鼠模型的经验。职业发展计划包括一段旨在发展基本神经科学知识和技术的指导研究，这将极大地增强他之前的培训。培训将包括学习研究技术和概念，并辅以教学培训、研讨会、实验室会议、期刊俱乐部、全国会议、顾问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指导。除了培养实验室技能外，职业发展计划还包括资助写作和负责任的研究行为方面的教学培训：研究计划的功能障碍。突触后蛋白编码基因称为SHANK 是一个新的、不断增长的科学领域，SHANK3 的缺乏会导致费兰-麦克德米德综合症 (PMS)，这是一种自闭症谱系障碍，他最近确定，在人类中的重复和小鼠的过度表达也会导致神经发育症状。在该提案中，申请人旨在通过遗传和化学遗传学方法研究导致Shank3过度表达表型的神经和分子机制，以逆转这些小鼠的运动表型。研究驱动过度表达表型的分子机制，并确定了 Shank3 和多巴胺受体信号传导之间的新联系。