The role of DISC 1 in synapse formation & function in the developing neocortex

DISC 1 在突触形成中的作用

• 批准号: 8046291
• 负责人: BRADY J MAHER
• 金额: $ 14.47万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-21 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8046291
• 关键词: Affect; Applications Grants; Binding; Brain; Bundling; Cells; Cognitive deficits; Connecticut; Development; Development Plans; Disease; Educational workshop; Electrophysiology (science); Electroporation; Etiology; Gene Expression; Genes; Goals; Growth Cones; Health; Hippocampus (Brain); In Vitro; Lead; Measurement; Measures; Mental Depression; Mental disorders; Mentored Research Scientist Development Award; Mentors; Molecular; Molecular Biology; Mood Disorders; Mus; Mutation; N-terminal; Neocortex; Neurobiology; PDE4B; Phenotype; Physiological; Physiology; Plasmids; Population; Prefrontal Cortex; Prevention; Proteins; Puberty; Public Health; RNA Interference; Rattus; Research; Research Personnel; Research Training; Resources; Rhodopsin; Role; Schizophrenia; Signal Transduction; Slice; Specific qualifier value; Staging; Susceptibility Gene; Synapses; Techniques; Testing; Training; base; career; career development; design; frontal lobe; genetic manipulation; gray matter; hippocampal pyramidal neuron; in utero; in vivo; mouse model; overexpression; postnatal; presynaptic; programs; research study; responsible research conduct; skills; synaptic function; synaptogenesis; therapeutic target

DESCRIPTION (provided by applicant): The applicant's long-term career goal is to develop into an independent investigator studying the etiology of schizophrenia. In order to achieve this objective, the applicant (Dr. Brady Maher) has prepared a Mentored Research Scientist Development Award (KOI) designed to: 1) acquire important technical and theoretical training in molecular biology and in utero electroporation techniques, while investigating gene expression and molecular interactions of schizophrenia susceptibility genes; and 2) prepare a competitive R01 grant proposal in order to establish an independent research program. The training proposed in the KOI application will be conducted in the context of a Career Development Plan. This Career Plan incorporates mentoring from an established molecular neuroscientist (Dr. Joe LoTurco),as well as important training opportunities for practical career development skills, workshops and Responsible Conduct of Research. The applicant as the commitment of resources and expertise from the Univ. of Connecticut, Dept. of Physiology and Neurobiology. The research portion of the Career Plan examines the role of DISCI, a schizophrenia susceptibility gene, in the development of cortical circuits. Dr. Maher's immediate goals are to develop an expertise in molecular biology and in utero electroporation. These techniques will be used to express various molecular constructs of DISCI into the developing mammalian brain to identify molecular signaling cascades important for cortical circuit development. Changes in circuit development will be measured functionally with electrophysiology. The proposed aims will test the hypothesis that mutations in DISCI lead to abnormal circuit formation that underlies schizophrenia. The results from these experiments are expected to increase our understanding of the impact that DISCI has on cortical development. This proposal is highly relevant to public health because approx. 1% of the population suffers from schizophrenia. Results from this proposal will identify important molecular cascades responsible for the etiology of schizophrenia and in so doing will provide potential therapeutic targets for its treatment. The overall training proposed will provide a basis upon which to develop a R01 proposal in Year 3. PUBLIC HEALTH RELEVANCE: The training and research proposed in this grant application are designed to explain how mutations in DISC1, a candidate susceptibility gene, affect the development of the prefrontal cortex. The results obtained from this proposal will provide potential therapeutic targets for the treatment and prevention of schizophrenia and other related disorders.

描述（由申请人提供）：申请人的长期职业目标是发展成为一名研究精神分裂症病因的独立研究者。为了实现这一目标，申请人（Brady Maher 博士）准备了指导研究科学家发展奖（KOI），旨在：1）在研究基因表达的同时，获得分子生物学和子宫内电穿孔技术方面的重要技术和理论培训和精神分裂症易感基因的分子相互作用； 2) 准备一份有竞争力的 R01 拨款提案，以建立独立的研究计划。 KOI 申请中提议的培训将在职业发展计划的背景下进行。该职业计划包含知名分子神经科学家（Joe LoTurco 博士）的指导，以及实用职业发展技能、研讨会和负责任的研究行为的重要培训机会。申请人作为大学资源和专业知识的承诺。康涅狄格州生理学和神经生物学系。职业规划的研究部分研究了 DISCI（一种精神分裂症易感基因）在皮质回路发育中的作用。 Maher 博士的近期目标是发展分子生物学和子宫电穿孔方面的专业知识。这些技术将用于将 DISCI 的各种分子结构表达到发育中的哺乳动物大脑中，以识别对皮质回路发育重要的分子信号级联。电路发育的变化将通过电生理学进行功能测量。拟议的目标将检验 DISCI 突变导致精神分裂症基础回路形成异常的假设。这些实验的结果预计将增加我们对 DISCI 对皮质发育影响的理解。该提案与公共卫生高度相关，因为大约。 1%的人口患有精神分裂症。该提案的结果将确定导致精神分裂症病因的重要分子级联反应，从而为其治疗提供潜在的治疗靶点。拟议的总体培训将为第 3 年制定 R01 提案奠定基础。 公共卫生相关性：本拨款申请中提出的培训和研究旨在解释候选易感基因 DISC1 的突变如何影响疾病的发展前额皮质。该提案获得的结果将为精神分裂症和其他相关疾病的治疗和预防提供潜在的治疗靶点。