ProMoTr: A Proteomics Center for MoTrPAC

ProMoTr：MoTrPAC 蛋白质组学中心

• 批准号: 9246899
• 负责人: Joshua N. Adkins
• 金额: $ 6.92万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-08 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9246899
• 关键词: Acetylation; Acylation; Animal Model; Animals; Biochemical; Bioinformatics; Blood; Catabolic Process; Chemicals; Chronic Disease; Clinical; Community Outreach; Complex; Data; Data Set; Development; Effectiveness; Elements; Energy Metabolism; Exercise; Foundations; Goals; Health Benefit; Homeostasis; Human; Lead; Leadership; Link; Lysine; Maps; Mass Spectrum Analysis; Measurement; Mediating; Metabolic Pathway; Metabolism; Modification; Molecular; Neuropeptides; Oxidation-Reduction; Phosphorylation; Physical Exercise; Physical activity; Physiological; Physiology; Plasma; Plasma Proteins; Post-Translational Protein Processing; Prevention; Protein Isoforms; Proteins; Proteomics; Quality Control; Reproducibility; Reproducibility of Results; Research; Resolution; Role; Sampling; Signal Pathway; Signal Transduction; Site; Stream; Stress; Sulfhydryl Compounds; Systems Biology; Technology; Tissue Sample; Tissues; Transducers; base; body system; computerized data processing; data acquisition; design; exosome; experience; health application; ion mobility; meetings; metabolomics; nanoscale; new technology; novel; pre-clinical; programs; protein expression; response; steroid hormone; success; transcriptomics; working group

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.

项目摘要 虽然身体活动在预防和减轻许多慢性疾病方面的健康益处 虽然几十年来一直有文献记载，但介导这些健康益处的分子机制仍然很差 明白为了在分子水平上理解身体活动的适应性反应， 全面表征蛋白质表达和翻译后修饰的动态变化 （PTM）在组织和循环生物流体中。PNNL蛋白质组学化学分析的总体目标 MoTrPAC中心（ProMoTr）将通过提供全面的发现和 血液中循环蛋白因子和相关PTM的后续靶向验证分析， MoTrPAC临床前动物研究中心和临床中心收集的多种组织类型。到 开发传感器的“分子图谱”，提供人体体力活动的影响， ProMoTr的整合蛋白质组学分析计划有两个主要重点。首先，我们将重点放在循环 基于已知的组织之间和组织内的串扰， 由身体活动引起的。其次，我们将研究组织和细胞水平对物理刺激的反应。 活性通过评估由蛋白质PTM介导的细胞内信号传导，包括蛋白质磷酸化， 可逆氧化还原修饰和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件，以发现和验证循环因子和细胞内 分子转换器; 2）提供生物信息学元素，以充分支持ProMoTr的需求， 统计设计、数据处理、分析、解释和传播; 3）提供行政管理 监督内部活动并提供与MoTrPAC中心的高级别协作互动的要素 和更广泛的财团。进行高质量可重复发现和验证的可行性 成千上万的组织样本的分析是建立在PNNL的成就记录之上的， 大规模整合蛋白质组学项目。PNNL的基础包括精细的质量控制、大规模的 计算和传播能力，我们在开发和部署 尖端的质谱技术，以及我们研究蛋白质PTM的能力， 与能量代谢密切相关。