Yale/NIDA Neuroproteomics Center

我们建议不断完善耶鲁/NIDA神经蛋白质组中心，为我们带来异常 耶鲁大学在蛋白质组学和大脑信号转导方面与来自8个州的神经科学家一起开展了强大的项目 美国各地的其他机构创建一个全国性的资源，该资源将合作确定适应性变化 在对滥用物质做出反应的蛋白质信号中。23名教职员工，拥有常设机构 对精神活性成瘾药物的分子作用的高度创新研究记录，以及 神经生物学的其他基本方面，将以独特的协同作用与凯克基金会合作 生物技术实验室创建该中心，其主题是“成瘾中信号改变的蛋白质组学”。 该中心将使用尖端蛋白质组学技术来分析神经元信号转导机制 以及这些过程中因药物滥用而发生的适应性变化。与联席董事 Angus Nairn(精神病学)和Kenneth Williams(Mol.生物群落。&Biochem。)在行政核心中， 该中心包括发现蛋白质组学(DPC)和靶向蛋白质组学(TPC)核心。生物物理技术 来自DPC的蛋白质图谱分析将扩展到功能领域，而来自 DPC将利用蛋白质组水平分析来提供越来越多的生物系统水平的方法。一个 生物统计和生物信息学核心(BBC)，包括高性能计算和生物信息学 耶鲁大学医学图书馆的支持计划将提供基本的支持，以利用每个 蛋白质组技术核心。试点研究项目核心是我们努力鼓励 强大的指导关系，将有助于吸引和培养未来杰出的科学家。 伴随药物成瘾而来的行为适应被认为是短期和长期的结果。 大脑奖励中心的适应性变化。因此，暴露在滥用药物中可以调节细胞内的信号传递。 改变基因表达、蛋白质翻译和蛋白质翻译后修饰的过程。 反复接触滥用药物会导致这些信号系统的稳定变化，这对 成瘾后大脑化学成分和结构的变化。该中心的研究目标包括 分析大麻、可卡因、尼古丁和阿片类药物对这些细胞内信号通路的作用 脑奖赏区域和单一类型神经元蛋白质组学分析方法的发展 这定义了作为滥用药物行为和成瘾特性基础的回路。目标和数据- 对与药物滥用行为有关的信号蛋白进行独立的MS分析将用于 以Motif为基础的“中下”MS/MS分析药物滥用对神经蛋白质组的影响 其他新的方法被用于研究蛋白质翻译后修饰并揭示 关键蛋白质的相互作用。英国广播公司的一项主要举措将是开发新的方法来 基因组、转录组和蛋白质组数据与脑区、细胞类型和等位基因特异性的整合。

We propose to continuously improve the Yale/NIDA Neuroproteomics Center that brings exceptionally strong Yale programs in proteomics and signal transduction in the brain together with neuroscientists from 8 other institutions across the U.S. to create a national resource that will collaborate to identify adaptive changes in protein signaling that occur in response to substances of abuse. Twenty-three faculty with established records of highly innovative research into the molecular actions of psychoactive addictive drugs, as well as of other basic aspects of neurobiology, will work together in a unique synergy with the Keck Foundation Biotechnology Laboratory to create the Center, whose theme is “Proteomics of Altered Signaling in Addiction”. The Center will use cutting edge proteomic technologies to analyze neuronal signal transduction mechanisms and the adaptive changes in these processes that occur in response to drugs of abuse. With Co-Directors Angus Nairn (Psychiatry) and Kenneth Williams (Mol. Biophys. & Biochem.) in the Administrative Core, the Center includes Discovery Proteomics (DPC) and Targeted Proteomics (TPC) Cores. Biophysical technologies from the DPC will extend protein profiling analyses into the functional domain while lipid analyses from the DPC will leverage proteome level analyses to provide an increasingly biological systems level approach. A Biostatistics and Bioinformatics Core (BBC) that includes high performance computing and the Bioinformatics Support Program in the Yale Medical Library will provide essential support that will leverage the value of each of the proteomic technology cores. A Pilot Research Project Core is a cornerstone in our efforts to encourage strong mentoring relationships that will help attract and train future outstanding scientists. 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 that alter gene expression, protein translation, and protein post-translational modifications. Repeated exposure to drugs of abuse leads to stable alterations in these signaling systems that are critical for the changes in brain chemistry and structure of the addicted brain. The Center's research goals include analysis of the actions of cannabis, cocaine, nicotine, and opioids on these intracellular signaling pathways in brain reward areas and development of methods that enable proteomic analysis of the single types of neurons that define the circuits that underlie the actions and addictive properties of drugs of abuse. Targeted and data- independent MS analyses of signaling proteins implicated in the actions of drugs of abuse will be used to analyze the impact of substance abuse on the neuroproteome with motif-based, “Middle-down” MS/MS, and other novel approaches being used to study protein post-translational modifications and to uncover the interactomes of key proteins. A major initiative of the BBC will be to develop novel methods for deep integration of genomic, transcriptomic, and proteomic data with brain region, cell type and allele-specificity.