ProMoTr: A Proteomics Center for MoTrPAC

ProMoTr：MoTrPAC 蛋白质组学中心

基本信息

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
项目类别：
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

项目摘要

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.

项目概要尽管体力活动在预防和缓解许多慢性疾病方面对健康有益虽然已有数十年的记录，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，有必要全面表征蛋白质表达和翻译后修饰的动态变化 (PTM) 存在于组织和循环生物液中。 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支持来支持该联盟随后对血液中的循环蛋白因子和相关 PTM 进行有针对性的验证分析 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”，提供人类身体活动的影响， ProMoTr 的综合蛋白质组学分析计划有两个主要重点。首先我们要关注的是流通领域根据组织之间和组织内已知的串扰在血浆和组织中发现的分泌因子体力活动造成的。其次，我们将研究组织和细胞水平对物理的反应通过评估蛋白质 PTM 介导的细胞内信号传导（包括蛋白质磷酸化）来评估活性，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件来发现和验证循环因子和细胞内分子传感器； 2) 提供生物信息学元件，全面支持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元素以及更广泛的财团。进行高质量可重复发现和验证的可行性对数万个组织样本进行的分析是建立在 PNNL 的成就记录之上的大规模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，我们在开发和部署方面公认的专业知识基于质谱的尖端技术，以及我们研究蛋白质 PTM 的能力与能量代谢密切相关。