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New Proteomic and Genome Engineering Approaches to Decipher Astrocyte Function at Synapses

破译星形胶质细胞突触功能的新蛋白质组学和基因组工程方法

基本信息

批准号：
9789247
负责人：
Cagla Eroglu
金额：
$ 70.53万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9789247
关键词：
Affect Age Astrocytes Biochemical Brain Brain Diseases Brain region C-terminal CRISPR/Cas technology Cell Adhesion Molecules Cell surface Chimeric Proteins Cognition Complement Complex Data Development Disease Disease model Evolution Functional disorder Future Gene Expression Genome engineering Goals Homeostasis Human Impairment Individual Knock-out Knowledge Label Lead Link Mass Spectrum Analysis Mediating Membrane Methods Molecular Molecular Profiling Monitor Mus Mutation N-terminal Nervous System Physiology Neuroglia Neurons Neurosciences Pathology Pathway interactions Problem Solving Process Property Proteins Proteome Proteomics Reaction Regulation Resources Role Science Specific qualifier value Structure Surface Synapses Synaptic Transmission Synaptosomes Techniques Testing Thinness Touch sensation Viral Work base blind brain cell cell type extracellular genome editing in vivo innovation insight mouse model nervous system disorder neuroregulation novel postsynaptic protein complex reconstitution synaptic function synaptogenesis tool

项目摘要

ABSTRACT Astrocytes are the most abundant glial cells in the human brain. Interactions of astrocytes with synapses via thin perisynaptic astrocytic processes are critical for proper synaptic connectivity and function. Each mouse astrocyte sends out an extensive array of processes that are estimated to contact over 100,000 synapses. The number of astrocytes and the extent of their interactions with synapses have increased throughout evolution, indicating a close link between astrocytes and cognition. Moreover, emerging evidence suggests that dysfunction of astrocyte-synapse interactions contributes to a variety of brain disorders. In contrast to neuronal synaptic structures, however, we are largely blind to the molecular composition and mechanisms of the astrocytic perisynaptic structures. Moreover, there is currently very little understanding of how mutations that disrupt astrocyte-synapse interactions lead to synaptic pathologies. This is in large part because, unlike neuronal synaptic structures, it has not been possible to purify and identify proteins enriched at subcellular regions of astrocytes. In this project, we will develop and utilize innovative proteomic and genome editing approaches to solve these problems, revealing the proteins and inner workings of astrocyte processes that associate with and modulate synapses. We anticipate these data will provide a new and unparalleled molecular framework for future studies on astrocyte- neuron interactions.

摘要