ProMoTr: A Proteomics Center for MoTrPAC

项目总结 尽管体育锻炼在预防和缓解许多慢性病方面对健康的好处 几十年来一直有文献记载，但调节这些健康益处的分子机制仍然很差 明白了。为了在分子水平上理解体力活动的适应性反应，有必要 全面描述蛋白质表达的动态变化和翻译后修饰 (PTMS)在组织和循环生物体液中。PNNL蛋白质组化学分析的总体目标 MoTrPAC中心(ProMoTr)将通过提供全面的发现和 中国人群血液循环蛋白因子及相关PTM的后续靶向验证分析 MoTrPAC临床前动物研究场地和临床中心收集的多种组织类型。至 开发一张提供人体体力活动影响的传感器的“分子图谱”。 ProMoTr的综合蛋白质组学分析计划有两个主要焦点。首先，我们将重点关注循环 根据已知的组织间和组织内的串扰，在血浆和组织中发现分泌因子 由体力活动引起的。第二，我们将研究组织和细胞水平对物理 通过评估由蛋白质PTMS介导的细胞内信号的活性，包括蛋白质磷酸化， 可逆氧化还原修饰，以及赖氨酸乙酰化和酰化。ProMoTr的具体目标是：1) 提供蛋白质组学化学分析元素，以发现和验证循环因子和细胞内 分子传感器；2)提供生物信息学元素，以充分支持ProMoTr在 统计设计、数据处理、分析、解释和传播；3)提供行政 元素来监督内部活动并提供与MoTrPAC中心的高级别协作交互 以及更广泛的财团。执行高质量、可重现的发现和验证的可行性 对数以万计的组织样本的分析是建立在PNNL完成 大规模的综合蛋白质组学计划。PNNL的基础包括精细化的质量控制，大规模的 计算和传播能力，我们在开发和部署 尖端的基于质谱学的技术，以及我们研究蛋白质PTM的能力 与能量代谢密切相关。

PROJECT SUMMARY Although the health benefits of physical activity in prevention and mitigation of many chronic diseases have been documented for decades, the molecular mechanisms mediating these health benefits are still poorly understood. To understand the adaptive response of physical activity at the molecular level, it is essential to comprehensively characterize the dynamic changes in protein expression and post-translational modifications (PTMs) in tissues and circulating biofluids. The overall objective of the PNNL Proteomics Chemical Analysis Center for MoTrPAC (ProMoTr) is to support the consortium by providing comprehensive discovery and subsequent targeted verification analyses of circulating protein factors in blood and associated PTMs in multiple tissue types collected by the Pre-clinical Animal Study Sites and Clinical Centers of MoTrPAC. To develop a `molecular map' of transducers that provide the impacts of physical activity in humans, the ProMoTr's integrative proteomics analysis plan has two major foci. First, we will focus on the circulating secreted factors found in blood plasma and tissues based on the known cross-talk between and within tissues resulting from physical activity. Second, we will investigate the tissue- and cellular- level response to physical activity by assessing intracellular signaling as mediated by protein PTMs, including protein phosphorylation, reversible redox modifications, and lysine acetylation and acylation. The Specific Aims of ProMoTr are: 1) to provide the Proteomics Chemical Analysis Element to discover and verify circulating factors and intracellular molecular transducers; 2) to provide the Bioinformatics Element to fully support the needs of ProMoTr in statistical design, data processing, analysis, interpretation, and dissemination; 3) to provide the Administrative Element to oversee internal activities and to provide high-level collaborative interactions with MoTrPAC centers and the broader consortium. The feasibility of performing high quality reproducible discovery and verification analyses on the scale of tens of thousands of tissue samples is built upon PNNL's record of accomplishment of large-scale integrative proteomics programs. The PNNL foundation includes refined quality control, large-scale computation, and dissemination capabilities, our recognized expertise in the development and deployment of cutting-edge mass spectrometry-based technologies, and our capabilities for studying protein PTMs that are closely linked with energy metabolism.