Core B: Proteomics and lipoprotein characterization core

核心 B：蛋白质组学和脂蛋白表征核心

• 批准号: 10642742
• 负责人: Tomas Vaisar
• 金额: $ 17.45万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10642742
• 关键词: Abbreviations; Apolipoprotein E; Atherosclerosis; Basic Science; Bioinformatics; Biological; Biological Assay; Calibration; Cardiovascular Diseases; Chylomicrons; Collaborations; Complex; Concentration measurement; Consultations; Data; Data Analyses; Data Set; Data Storage and Retrieval; Databases; Development; Diabetes Mellitus; Diabetic Angiopathies; Disease; Electrospray Ionization; Ensure; Family; Goals; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Human; Human Resources; IDL lipoproteins; Individual; Isotopes; Label; Laboratories; Lipoproteins; Liquid Chromatography; Low-Density Lipoproteins; Mass Spectrum Analysis; Measurement; Measures; Metabolism; Methods; Modernization; Molecular; Monitor; New York; Pathogenesis; Pathway Analysis; Physiological; Procedures; Process; Program Research Project Grants; Proteins; Proteome; Proteomics; Reaction; Reproducibility; Research; Research Personnel; Risk Factors; Scientist; Services; Shotguns; Site; Standardization; Systems Biology; Techniques; Technology; Translational Research; Triglycerides; Very low density lipoprotein; analytical method; analytical tool; apolipoprotein B-48; bioinformatics tool; complex data; cost; cost effectiveness; instrument; instrumentation; interest; ion mobility; link protein; liquid chromatography mass spectrometry; mouse model; novel; novel strategies; particle; phenotypic data; program costs; programs; protein complex; tool; translational study

The proteomics and lipoprotein characterization core (Core B) will provide the powerful tools of modern mass spectrometry and complex data set analysis to Program Project Grant (PPG) investigators. The Core will also provide lipoprotein isolation, and measurements of lipoprotein particle concentration and size using calibrated ion mobility analysis. The Core will permit structural identification and quantitation of lipoproteins including remnant lipoprotein particles (RLPs), as well as VLDL, LDL and HDL, and measurement of lipoprotein particle number of these lipoprotein classes using calibrated ion mobility analysis. Core personnel are proficient in liquid chromatography-electrospray ionization-MS/MS analysis (shotgun proteomics) of complex biological mixtures of proteins, with a particular emphasis on the lipoprotein proteomes and on the quantification of their protein cargo using targeted LC-MSMS analysis. The Core Director established precise methods for quantitation of HDL proteome and applied them to quantification of the HDL proteome in large translational studies and will apply the same methods to other lipoprotein classes through Core B. The unique calibrated ion mobility analysis method measures HDL particle number and 5 subspecies of HDL particles, as well as proatherogenic particles like RLPs, and small dense LDL. We anticipate that all investigators will take advantage of these capabilities. In addition to providing instrumental capabilities and bioinformatics tools, Core B staff will provide consultation and collaboration on the application of mass spectrometry and lipoprotein particle concentration measurements to the Program Project, and integration and analysis of complex datasets. This will include development of new analytical methods targeted at achieving the research objectives of the Program’s investigators. Core B will optimize the efficiency and cost-effectiveness through which these services are provided to PPG investigators by providing a central laboratory. This avoids the need for individual PPG investigators to maintain the required instrumentation in their own laboratories, avoids the high cost of commercial mass spectrometric services, and will ensure consistency between analyses for different project sites (Seattle, St. Louis, and New York). By centralizing and standardizing procedures, Core B will provide a common set of analytical tools that will lead to a unified understanding of molecular mechanisms involved in the physiologic and pathophysiologic processes of diabetic vascular disease.

蛋白质组学和脂蛋白表征核心（核心B）将为现代蛋白质组学研究提供强有力的工具。 质谱和复杂的数据集分析，以计划项目资助（PPG）的研究人员。芯会 还提供脂蛋白分离和脂蛋白颗粒浓度和大小的测量， 校准的离子迁移率分析。核心将允许脂蛋白的结构鉴定和定量 包括残余脂蛋白颗粒（RLP），以及VLDL、LDL和HDL， 使用校准的离子迁移率分析这些脂蛋白类别的脂蛋白颗粒数。 核心人员精通液相色谱-电喷雾电离-MS/MS分析（鸟枪法 蛋白质组学）的蛋白质的复杂生物混合物，特别强调脂蛋白蛋白质组 以及使用靶向LC-MSMS分析定量其蛋白质货物。核心导演 建立了精确的HDL蛋白质组定量方法，并将其应用于HDL的定量 蛋白质组在大型翻译研究，并将适用于其他脂蛋白类相同的方法，通过 核心B。独特的校准离子迁移率分析方法测量HDL颗粒数量和5个亚种 高密度脂蛋白颗粒，以及致动脉粥样硬化颗粒，如RLP，和小而密的低密度脂蛋白。我们预计， 调查人员将利用这些能力。 核心B人员除了提供仪器能力和生物信息学工具外，还将提供咨询 并在质谱和脂蛋白颗粒浓度测量的应用方面进行合作 计划项目，以及复杂数据集的集成和分析。这将包括开发新的 旨在实现该计划的研究人员的研究目标的分析方法。 核心B将优化向PPG提供这些服务的效率和成本效益 研究人员通过提供中心实验室。这避免了单个PPG研究者需要 在自己的实验室维护所需的仪器，避免了商业规模的高成本 光谱服务，并将确保不同项目地点（西雅图，圣路易斯）分析之间的一致性。 Louis和纽约）。通过集中和标准化程序，核心B将提供一套通用的 分析工具，这将导致在生理参与分子机制的统一理解， 糖尿病血管病变的病理生理过程。