ProMoTr: A Proteomics Center for MoTrPAC

ProMoTr：MoTrPAC 蛋白质组学中心

• 批准号: 10316999
• 负责人: Joshua N. Adkins
• 金额: $ 268.8万
• 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 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10316999
• 关键词: Acetylation; Acylation; Animal Model; Animals; Biochemical; Bioinformatics; Blood; Catabolic Process; Chemicals; Chronic Disease; Clinical; Community Outreach; Complex; Data; 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; Stress; Sulfhydryl Compounds; Systems Biology; Technology; Tissue Sample; Tissues; Transducers; base; body system; clinical center; computerized data processing; data acquisition; data streams; design; exosome; experience; health application; ion mobility; meetings; metabolomics; multidimensional data; multiple omics; 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 尽管体育活动对预防和缓解许多慢性疾病的健康益处具有 已经记录了数十年，介导这些健康益处的分子机制仍然很差 理解。要了解分子水平的体育活动的适应性反应，必须 全面地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（促销）中心是通过提供全面的发现和 随后对血液中循环蛋白质因子和相关PTM中循环蛋白质因子的靶向验证分析 MOTRPAC的临床前动物研究地点和临床中心收集的多种组织类型。到 开发换能器的“分子图”，该换能器提供了人类体育锻炼的影响， 促销的综合蛋白质组学分析计划具有两个主要焦点。首先，我们将专注于循环 根据已知的组织和组织中的串扰，在血浆和组织中发现的分泌因子 由体育锻炼产生。其次，我们将研究组织和细胞水平对物理的反应 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， 可逆的氧化还原修饰以及赖氨酸乙酰化和酰化。促销的具体目的是：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 分子传感器； 2）提供生物信息学元素以充分满足促销的需求 统计设计，数据处理，分析，解释和传播； 3）提供行政 监督内部活动并与MOTRPAC中心提供高级协作互动的要素 和更广泛的财团。执行高质量可重复的发现和验证的可行性 基于PNNL的成就记录，建立了成千上万的组织样本规模的分析 大规模综合蛋白质组学计划。 PNNL基础包括精制质量控制，大规模控制 计算和传播功能，我们在开发和部署方面公认的专业知识 最先进的质谱技术，以及我们研究蛋白质PTM的能力 与能量代谢密切相关。

项目成果

Characterization of cellular oxidative stress response by stoichiometric redox proteomics.

通过化学计量氧化还原蛋白质组学表征细胞氧化应激反应。

• DOI: 10.1152/ajpcell.00040.2020
• 发表时间: 2021
• 期刊: American journal of physiology. Cell physiology
• 作者: Zhang,Tong;Gaffrey,MatthewJ;Li,Xiaolu;Qian,Wei-Jun
• 通讯作者: Qian,Wei-Jun

A deep redox proteome profiling workflow and its application to skeletal muscle of a Duchenne Muscular Dystrophy model.

• DOI: 10.1016/j.freeradbiomed.2022.10.300
• 发表时间: 2022-11-20
• 期刊: FREE RADICAL BIOLOGY AND MEDICINE
• 影响因子: 7.4
• 作者: Day, Nicholas J.;Zhang, Tong;Gaffrey, Matthew J.;Zhao, Rui;Fillmore, Thomas L.;Moore, Ronald J.;Rodney, George G.;Qian, Wei-Jun
• 通讯作者: Qian, Wei-Jun

Assessment of TMT Labeling Efficiency in Large-Scale Quantitative Proteomics: The Critical Effect of Sample pH.

• DOI: 10.1021/acsomega.1c00776
• 发表时间: 2021-05-18
• 期刊: ACS omega
• 影响因子: 4.1
• 作者: Hutchinson-Bunch C;Sanford JA;Hansen JR;Gritsenko MA;Rodland KD;Piehowski PD;Qian WJ;Adkins JN
• 通讯作者: Adkins JN