Molecular Analysis of Developmental Brain Disorders Associated with Synaptic Pathology

与突触病理学相关的发育性脑疾病的分子分析

• 批准号: 10585092
• 负责人: SCOTT H SODERLING
• 金额: $ 75.26万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-16 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10585092
• 关键词: Animals; Anxiety; Axon; Behavior; Biological; Biology; Biotin; Brain; Brain Diseases; Buffers; Cells; Chimeric Proteins; Clustered Regularly Interspaced Short Palindromic Repeats; Code; Complex; Coupled; DNA Sequence Alteration; Data; Development; Disease; Engineering; Etiology; Exhibits; Face; Functional disorder; Future; Gene Expression; Genes; Genetic; Genome engineering; Genotype; Goals; Grant; Human; Human Genetics; Injections; Knowledge; Label; Lead; Maps; Measures; Mediating; Methods; Modeling; Molecular; Molecular Analysis; Mus; Mutation; Neurons; Outcome; Pathogenesis; Pathogenicity; Pathology; Pathway interactions; Patients; Phenotype; Problem Solving; Proteins; Proteome; Proteomics; Publishing; Structure; Subcellular structure; Synapses; Synaptic Transmission; Synaptic plasticity; Testing; Tissues; Ultrasonics; Variant; Viral; Work; autism spectrum disorder; base; behavioral outcome; burden of illness; cell type; disorder risk; driver mutation; epigenome; gene interaction; genetic variant; in vitro Assay; in vivo; innovation; insight; new technology; novel; novel strategies; prediction algorithm; predictive test; protein complex; protein protein interaction; protein structure prediction; repetitive behavior; response; risk variant; single cell analysis; single cell sequencing; single-cell RNA sequencing; success; vocalization

ABSTRACT The molecular mechanisms of synaptopathy that arise downstream of the large number of gene conferring risk for these disorders remains unclear. Particularly, how different risk genes may segregate into common molecular mechanisms has been challenging to identify. Likewise, how genetic missense variants result in pathology remains an enigma. These gaps in knowledge pose a significant barrier to the field and limit our ability to envision stratagies to ameliorate pathogenesis. In this project, we will develop and utilize innovative proteomic, scRNA-seq, and genome engineering approaches to solve these problems at larger scales than previously possible in animals. We anticipate these data will provide a new and unparalleled molecular framework for ASD and related disorders as well as future studies on new targets to beneficially modulate behavior.

摘要