Yale/NIDA Neuroproteomics Research Center

描述(由申请人提供)：我们建议维持并继续改进耶鲁大学医学院的NIDA神经蛋白质组学中心。来自耶鲁大学和其他机构的教职员工(芝加哥大学康涅狄格州，洛克菲勒大学，斯坦福大学，在精神刺激剂和精神药物的分子作用以及神经生物学的其他基本方面都有既定研究记录的NIDA)将继续与W.M.凯克基金会实验室的成员合作，创建NIDA神经蛋白质组学中心。该中心的主要目标是应用高通量、最先进的蛋白质组学方法来分析因滥用药物而发生的神经元蛋白表达和调节的适应性变化。此外，该中心将为中心成员提供蛋白质组学技术方面的培训，并将应用新的蛋白质组学技术来回答与药物滥用行为有关的生物学问题。在管理核心的Kenneth Williams博士(中心主任)和Angus Nairn博士(精神病学合作调查员)的指导下，该中心将包括一个蛋白质图谱和鉴定核心，一个蛋白质翻译后鉴定和图谱核心，以及一个目标蛋白质组学核心。脂肪和生物物理分析将包括在蛋白质图谱核心中。最后，蛋白质数据库、生物统计学、生物信息学和高性能计算核心将提供基本支持，从而积极利用每个蛋白质组技术核心的价值。与药物成瘾相关的行为适应被认为是大脑奖励中心的短期和长期适应性变化的结果。因此，暴露在滥用药物中调节细胞内的信号过程，进而导致基因表达、蛋白质翻译和蛋白质翻译后修饰的改变。反复接触滥用药物会导致这些信号系统发生长期、稳定的变化，这对成瘾的大脑化学和结构的变化至关重要。该中心通过其多学科和协作组织，将耶鲁大学的教职员工和他们的合作者聚集在一起，以更深入地了解神经元信号传递过程的机制，以及滥用药物如何改变这些信号机制。该中心支持的研究的具体目标将包括分析精神刺激剂、可卡因和苯丙胺、尼古丁和鸦片类药物的作用。新开发的方法将被应用于研究蛋白质磷酸化和神经元蛋白质的其他翻译后修饰，以及对与药物滥用行为有关的神经元蛋白质的有针对性的分析。

DESCRIPTION (provided by applicant): We propose to maintain and to continuously improve the NIDA Neuroproteomics Center at the Yale University School of Medicine. Faculty members from Yale and other institutions (Univ. Chicago, Univ. Connecticut, Rockefeller Univ., Stanford Univ., Univ. Texas) with established records of research into the molecular actions of psychostimulants and psychotropic drugs, as well as of other basic aspects of neurobiology, will continue to work together with members of the W.M. Keck Foundation Laboratory to create the NIDA Neuroproteomics Center. The main goal of the Center is to apply high-throughput, state-of-the-art proteomic methods to analyze adaptive changes in neuronal protein expression and regulation that occur in response to drugs of abuse. In addition, the Center will provide training in proteomics technologies for members of the Center, and will apply new proteomics technologies to answer biological questions related to the actions of drugs of abuse. Under the direction of Dr. Kenneth Williams (Center Director) and Dr. Angus Nairn (Co-Investigator, Psychiatry) in the Administration Core, the Center will include a Protein Profiling and Identification Core, a Protein Post-translational Identification and Profiling Core, and a Targeted Proteomics Core. Lipid and Biophysics analyses will be included in the Protein Profiling Core. Finally, a Protein Database, Biostatistics, Bioinformatics and a High Performance Computing Core will provide essential support that will positively leverage the value of each of the proteomic technology cores. The behavioral adaptations that accompany drug addiction are believed to result from both short and long-term adaptive changes in brain reward centers. Thus, exposure to drugs of abuse regulates intracellular signaling processes and in turn results in alteration of gene expression, protein translation and post-translational modifications of proteins. Repeated exposure to drugs of abuse leads to long-term, stable alterations in these signaling systems that are critical for the changes in brain chemistry and structure of the addicted brain. The Center, through its multidisciplinary and collaborative organization, brings together Yale faculty and their collaborators to gain a deeper insight into the mechanisms of neuronal signaling processes and into how drugs of abuse alter these signaling mechanisms. Specific goals of the research supported by the Center will include analysis of the actions of the psychostimulants, cocaine and amphetamine, nicotine and opiates. Newly developed methods will be applied to the study of protein phosphorylation and other post-translational modifications of neuronal proteins, as well as to the targeted analysis of neuronal proteins implicated in the actions of drugs of abuse.