Yale/NIDA Neuroproteomics Research Center

项目描述（申请人提供）：我们建议在耶鲁大学医学院建立NIDA神经蛋白质组学研究中心。超过20名教师与精神兴奋剂和精神药物的分子作用的研究历史，以及神经生物学的其他基本方面，将与WM一起工作。凯克基金会生物技术资源实验室创建神经蛋白质组学中心。该中心的主要目标将是应用高通量，最先进的蛋白质组学技术来分析神经元蛋白质表达和调节的适应性变化，这些变化是对滥用药物的反应。此外，该中心将提供蛋白质组学技术方面的培训，并将改进现有的和开发新的蛋白质组学技术，这些技术可应用于与滥用药物的行为有关的生物学问题。该中心将包括五个核心：蛋白质分离和分析，蛋白质鉴定，蛋白质微阵列，生物信息学和生物统计学以及管理。蛋白质分离核心中包含的“脂质组学”组件也将允许分析细胞脂质。伴随药物成瘾的行为适应被认为是大脑奖赏中心短期和长期适应性变化的结果。迄今为止，药物滥用的分子研究已经阐明了成瘾大脑中发生的一些转录变化。然而，很少有人知道滥用药物对神经元蛋白质组的影响。该中心将通过其高度跨学科和协作的组织，汇集耶鲁大学的教师与互补的专业知识，以获得更深入的洞察如何滥用药物改变表达和蛋白质的翻译后修饰在全球范围内。将使用的方法将包括基于MALDI-MS的生物标志物分析、二维色谱、差示（荧光）凝胶电泳（DIGE）、同位素编码亲和标签（ICAT）和抗体微阵列。还将开发用于研究脑磷酸化蛋白质组的方法，这些方法将应用于滥用药物的作用的研究。该中心支持的研究的具体目标包括分析鸦片制剂的作用;精神兴奋剂，可卡因和安非他明;以及尼古丁对蛋白质表达的影响。其他研究将集中在蛋白质组的变化，发生前和突触后的药物滥用的行动。

DESCRIPTION (provided by applicant): We propose to establish a NIDA Neuroproteomics Research Center at the Yale University School of Medicine. More than 20 faculty members with an established history of studies of the molecular actions of psychostimulants and psychotropic drugs, as well as of other basic aspects of neurobiology, will work together with the W.M. Keck Foundation Biotechnology Resource Laboratory to create the Neuroproteomics Center. The main goal of the Center will be to apply high-throughput, state-of-the-art proteomic technologies 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, and will improve existing and develop new proteomies technologies that can be applied to biological questions related to the actions of drugs of abuse. The Center will include five cores: Protein Separation and Profiling, Protein Identification, Protein Microarray, Bioinformatics and Biostatistics, and Administration. A "lipidomics" component, included in the Protein Separation Core, will also allow the analysis of cellular lipids. The behavioral adaptations that accompany drug addiction are believed to result from both short and longterm adaptive changes in brain reward centers. To date, molecular studies of drugs of abuse have elucidated some of the transcriptional changes that occur in the addicted brain. However, little is known about the effects of drugs of abuse on the neuronal proteome. The Center will, through its highly interdisciplinary and collaborative organization, bring together Yale faculty with complementary expertise to gain a far deeper insight into how drugs of abuse alter expression and post-translational modification of proteins on a global scale. Methods that will be used will include MALDI-MS based biomarker analysis, two-dimensional chromatography, differential (fluorescence) gel electrophoresis (DIGE), isotope-coded affinity tag (ICAT), and antibody microarrays. Methods also will be developed for studying the brain phosphoproteome and these will be applied to studies of the actions of drugs of abuse. Specific goals of the research supported by the Center include analysis of the actions of opiates; the psychostimulants, cocaine and amphetamine; and nicotine on protein expression. Other studies will focus on the proteomic changes that occur both pre- and post-synaptically following the actions of drugs of abuse.