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

描述（由申请人提供）：成瘾的发展涉及多巴胺能奖赏通路和下游负面变化，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处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大脑内高度复杂的细胞和组织以及神经元回路。为了更好地理解这一过程，需要蛋白质组学方法，这反过来又需要更好的检测试剂，用于包括2,000多种不同蛋白质的突触蛋白质组。我们建议使用我们的专有酵母展示抗体库开发良好的特点，高亲和力，特异性抗体对面板的突触蛋白，其中许多已被证明是调制响应阿片类药物管理。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，并用于探测小鼠模型中给药后这些蛋白的变化。长期目标是利用我们的酵母展示/抗体库系统开发用于整个突触蛋白质组的新型高质量检测试剂，以更好地绘制成瘾潜在的关键变化。

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.