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

描述(申请人提供)：成瘾的发展涉及多巴胺能奖赏途径和下游的负面变化，导致渴望和重复的自我管理。很明显，这个过程涉及突触连接处神经元可塑性的变化，但在蛋白质水平上导致依赖和与戒断相关的负面反应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组织以及神经元电路。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突触蛋白质组检测试剂，该蛋白质组由2000多种不同的蛋白质组成。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良好、高亲和力的特异性抗体，其中许多蛋白已被证明对阿片类药物的使用有调节作用。在这项I/II阶段的研究中，将开发针对一组约150个突触蛋白的抗体，并将其用于在小鼠模型中探索给药后这些蛋白的变化。我们的长期目标是利用我们的酵母展示/抗体库系统开发针对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.