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Molecular Genetic Tools for Transneuronal Transfer with Transactivation

用于跨神经元转移和反式激活的分子遗传学工具

基本信息

批准号：
9000760
负责人：
HAIG S KESHISHIAN
金额：
$ 24.98万
依托单位：
YALE UNIVERSITY
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：
2015-03-01 至 2018-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9000760
关键词：
Acute Address Amplifiers Carrier Proteins Cells Chimeric Proteins Communities Development Drosophila genus Effectiveness Electrophysiology (science)Endocytosis Enhancers Epitopes Foundations Future Gene Amplification Gene Expression Gene Expression Profile Genes Genetic Genetic Engineering Genetic Models Goals Health Image Ion Channel Lectin Link Mammals Maps Methodology Methods Modification Molecular Molecular Genetics Nervous system structure Neurons Neurophysiology - biologic function Neurosciences Organism Plants Proteins Reporter Reporting Research Resource Sharing Series Source Speed Synapses Synaptic Transmission System Systems Analysis Technology Testing Transactivation Transcriptional Activation Transgenes Transgenic Animals Transgenic Organisms Validation base genetic approach improved in vivo innovation meetings member neural circuit neurodevelopment neuroregulation new technology novel optogenetics postsynaptic presynaptic neurons promoter relating to nervous system tool trafficking

项目摘要

DESCRIPTION (provided by applicant): This proposal describes a novel genetic method for mapping and experimentally controlling the neurons that are functionally connected within neural circuits. The approach used involves a modified plant-derived lectin carrier that is released in an activity-dependent fashion from presynaptic neurons, and is endocytosed by post- neuronal partners. The carrier lectin molecule has been modified from its native form to improve its efficiency of transfer and trafficking within the neuron. The carrier lectin is fused t various molecular cargoes, including a variety of fluorescent proteins, as well as epitope tags. Significantly, we use the carrier to transfer GV16, for the activation of UAS effector transgenes. To our knowledge this is the first example of a bipartite gene expression system that can be targeted to the members of a neural circuit. This method, which we term ITEM (Inducible Transneuronal Expression with Amplification), includes potent gene amplification. Using ITEM we can activate specific transgenes within synaptic partners, opening a new technology where the neurons of specific neural circuits can have specific transgenes activated in a genetic fashion. The project includes a series of proposed improvements to the technology, and functional tests as to its effectiveness as a tool to control gene expression in neural circuits.

描述（由申请人提供）：该提案描述了一种新的遗传方法，用于映射和实验控制在神经回路内功能连接的神经元。所使用的方法涉及修饰的植物来源的凝集素载体，其以活性依赖性方式从突触前神经元释放，并被后神经元伴侣内吞。载体凝集素分子已经从其天然形式进行了修饰，以提高其在神经元内转移和运输的效率。载体凝集素与各种分子货物融合，包括各种荧光蛋白以及表位标签。值得注意的是，我们使用载体转移GV 16，用于激活UAS效应转基因。据我们所知，这是第一个可以靶向神经回路成员的二分基因表达系统的例子。这种方法，我们称之为项目（诱导跨神经元表达与扩增），包括有效的基因扩增。使用ITEM，我们可以激活突触伴侣中的特定转基因，开启了一项新技术，其中特定神经回路的神经元可以以遗传方式激活特定的转基因。该项目包括一系列对该技术的改进建议，以及对其作为控制神经回路中基因表达的工具的有效性进行功能测试。