Novel approach for developing antibody reagents to probe changes in the synapse p

开发抗体试剂来探测突触 p 变化的新方法

基本信息

批准号：
8522999
负责人：
Lakshmi A Devi
金额：
$ 22.5万
依托单位：
AVANTGEN, INC.
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-05-01 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8522999
关键词：
12 year old Affect Affinity Alcohols Aliquot Antibodies Antibody Affinity Antigens Binding Biological Assay Brain Budgets Cell Separation Cells Chimeric Proteins Complex Custom Dependence Detection Development Dopamine Drug Addiction Drug or chemical Tissue Distribution Enzyme-Linked Immunosorbent Assay Epitopes Escherichia coli Fluorescence-Activated Cell Sorting Generations Genes Goals Harvest Health Human Immunoglobulin Variable Region Immunoprecipitation Individual Kinetics Label Laboratories Lead Libraries Maps Methods Modeling Molecular Morphine Morphine Dependence Mouse Protein Mus Nature Nerve Neuronal Plasticity Opiate Addiction Opiates Outcome Pathway interactions Pharmaceutical Preparations Phase Population Process Production Proteins Proteome Proteomics Protocols documentation Reagent Research Rewards Sampling Self Administration Signal Transduction Site Sorting - Cell Movement Specificity Synapses System Technology Testing Time Tissue Sample Tissues Western Blotting Withdrawal Withdrawal Symptom Yeasts addiction base craving experience expression vector improved magnetic beads mouse model neuronal circuitry novel novel strategies phase 1 study phase 2 study public health relevance response tool

项目摘要

DESCRIPTION (provided by applicant): The development of addiction involves the dopaminergic reward pathway and downstream negative changes that lead to craving and repeat self-administration. While it is clear this process involves changes in neuronal plasticity t the synapse junction, the exact changes at the protein level leading to the development of dependence and negative responses associated with withdrawal are poorly understood, in large part because of the highly complex cellular and tissue organization and neuronal circuitry within the brain. To better understand this process requires proteomic approaches, which in turn require better detection reagents for the synapse proteome which comprises over 2,000 different proteins. We propose to use our proprietary yeast display antibody library to develop well-characterized, high-affinity, specific antibodies against a panel of synapse proteins, many of which have been shown to be modulated in response to opiate administration. In this Phase I/II study, antibodies against a panel of about 150 synaptic proteins will be developed and used to probe the changes of these proteins upon drug administration in a mouse model. The long-term goal is to develop novel and high quality detection reagents for the entire synapse proteome with our yeast display/antibody library system to better map the critical changes underlying addiction.

描述（由申请人提供）：成瘾的发展涉及多巴胺能奖励途径和下游负面变化，这些变化导致渴望和重复自我给药。虽然很明显这个过程涉及突触连接的神经元可塑性的变化，但导致依赖性发展和与戒断相关的负面反应的蛋白质水平的确切变化却知之甚少，这在很大程度上是因为高度复杂的细胞和组织大脑内的组织和神经元回路。为了更好地理解这一过程，需要蛋白质组学方法，而蛋白质组学方法又需要更好的突触蛋白质组检测试剂，突触蛋白质组包含 2,000 多种不同的蛋白质。我们建议使用我们专有的酵母展示抗体库来开发针对一组突触蛋白的特征明确、高亲和力的特异性抗体，其中许多突触蛋白已被证明可以响应阿片类药物的给药而受到调节。在这项 I/II 期研究中，将开发针对一组约 150 种突触蛋白的抗体，并用于在小鼠模型中探测这些蛋白在给药后的变化。长期目标是利用我们的酵母展示/抗体库系统为整个突触蛋白质组开发新颖且高质量的检测试剂，以更好地绘制成瘾背后的关键变化。