Analytical Core

分析核心

• 批准号: 8379010
• 负责人: Henri Brunengraber
• 金额: $ 40.75万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8379010
• 关键词: Acyl Coenzyme A; Animal Experiments; Biochemical; Biological Markers; Body Fluids; Carbon; Citric Acid Cycle; Clinical; Complement; Data; Enzymes; Esters; Hydroxy Acids; Individual; Isotopes; Kinetics; Label; Link; Mass Spectrum Analysis; Measurement; Mentors; Metabolic; Metabolism; Mus; Organ; Pathway interactions; Pattern; Phenotype; Physiological Processes; Procedures; Regulation; Research Design; Scientist; Shipping; Ships; Techniques; Testing; Tissues; Training; Variant; acylcarnitine; design; in vivo; metabolic abnormality assessment; metabolomics; stable isotope; web page

ABSTRACT: Core C: Analytical & Metabolomic The Case MMPC specializes in the use of stable isotopes, mass spectrometry and metabolomics to investigate the regulation of pathways of intermediary metabolism in vivo and ex vivo. Emphasis is on quantitative measurements of inter-organ and intra-organ carbon fluxes. Our strategy links clinical-type studies (limited to body fluids) and pure biochemical studies (such as the kinetics of purified enzymes). The association of metabolomics and mass isotopomer analysis provides a wealth of information on the regulation of known pathways. It also allows to identify new pathways. Metabolomics developed initially as a non-targeted strategy aimed at gathering sufficient data on a (patho)physiological process (biomarkers), so that one could formulate hypotheses to be tested. A variant of this strategy is to target metabolomic studies to classes of compounds, the concentrations and labeling patterns of which can provide much new information: citric acid cycle intermediates, (hydroxy)acids, acyl-CoA esters, acylcarnitine esters. The Case MMPC occupies a specialized niche in the MMPC consortium, complementing the expertise of the other centers, but with a healthy degree of overlap with the Vanderbiit, Yale, Dallas and Cincinnati centers. The specific aims of the Analytical & Metabolomic Core are: 1. To help users in the design, implementation, analytical procedures and interpretation of metabolic studies conducted either, (i) entirely in the user's lab, (ii) entirely in the Case MMPC, or (iii) partly in the user's lab (animal experiments) and partly in the MMPC (analyses of tissues and body fluids shipped from the user's lab). 2. To set up, at users' request, tests and analytical procedures not currently listed on the web page of the Case MMPC. 3. To develop analytical techniques and isotopic strategies in anticipation of users' needs. 4. To train US and foreign scientists in the proper use of isotopes for metabolic studies. This training takes to form of (i) mentoring individual users, and (ii) contribution to an annual MMPC course.

摘要：核心 C：分析和代谢组学 Case MMPC 专门利用稳定同位素、质谱和代谢组学来研究体内和离体中间代谢途径的调节。重点是器官间和器官内碳通量的定量测量。我们的策略将临床类型研究（仅限于体液）和纯生化研究（例如纯化酶的动力学）联系起来。该协会的 代谢组学和质量同位素异构体分析提供了有关已知途径调节的丰富信息。它还可以识别新的途径。代谢组学最初是作为一种非靶向策略开发的，旨在收集有关（病理）生理过程（生物标志物）的足够数据，以便可以制定要测试的假设。该策略的一个变体是将代谢组学研究针对化合物类别， 其浓度和标记模式可以提供许多新信息：柠檬酸循环中间体、（羟基）酸、酰基辅酶A酯、酰基肉碱酯。 Case MMPC 在 MMPC 联盟中占有一席之地，补充了其他中心的专业知识，但与范德比特、耶鲁、达拉斯和辛辛那提中心有一定程度的重叠。 分析和代谢组学核心的具体目标是： 1. 帮助用户设计、实施、分析程序和解释代谢研究，(i) 完全在用户实验室中，(ii) 完全在 Case MMPC 中，或 (iii) 部分在用户实验室（动物实验）和部分在 MMPC 中（对从用户实验室运送的组织和体液进行分析）。 2. 根据用户的要求，建立目前未在案例 MMPC 网页上列出的测试和分析程序。 3. 根据用户需求开发分析技术和同位素策略。 4. 培训美国和外国科学家正确使用同位素进行代谢研究。该培训采取以下形式：(i) 指导个人用户，以及 (ii) 为年度 MMPC 课程做出贡献。