Case Mouse Metabolic Phenotyping Center

凯斯小鼠代谢表型中心

• 批准号: 9173671
• 负责人: Henri Brunengraber
• 金额: $ 30.91万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-25 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9173671
• 关键词: Body Fluids; Chronic Disease; Complement; Complex; Core Facility; Custom; Development; Diabetes Mellitus; Educational process of instructing; Elements; Faculty; Fee-for-Service Plans; Genetically Engineered Mouse; Goals; Health Benefit; Individual; Inflammation; Institution; International; Investigation; Isotopes; Kinetics; Laboratories; Learning; Lipid Peroxidation; Mass Spectrum Analysis; Measurement; Measures; Metabolic; Metabolic Diseases; Metabolism; Mission; Modus; Morphologic artifacts; Mus; National Institute of Diabetes and Digestive and Kidney Diseases; Obesity; Ohio; Oxidative Stress; Pathway interactions; Pattern; Plague; Planning Techniques; Procedures; Protocols documentation; Request for Applications; Research; Research Personnel; Sampling; Services; Techniques; Technology; Time; Tissues; Tracer; Training; Training and Education; Universities; Work; design; innovation; metabolic abnormality assessment; metabolic phenotype; metabolomics; mouse model; operation; programs; research study; stable isotope

ABSTRACT The mission of the Case-MMPC is to facilitate phenotypic characterization of mice for investigators studying metabolic diseases, with an emphasis and prioritization on diabetes and obesity. We work within the MMPC Consortium to complement and partially overlap the activities of the other six Centers. Our niche is the measurement and interpretation of metabolic fluxes and metabolomic patterns with the help of stable isotope tracer techniques and mass spectrometry, with emphasis on the avoidance of artifacts that often plague such protocols. The combination of metabolomics and stable isotope technology allows the discovery of new pathways and new regulatory mechanisms. This approach was pioneered at the Case-MMPC and has since gained favor with investigators around the world. Our Center was also instrumental in the development of the NIDDK-sponsored annual course on “Use of Isotopes for Metabolic Studies”, which will be taught for the 8th time in November 2015 by 11 faculty from MMPCs and US universities, and draws an international attendance. The Case-MMPC is currently in its 9th year of operation. This application requests support for increasing the capacity of the Center, expanding the repertoire of tracers provided and metabolites measured to include oxidative stress and inflammation-related pathways. Specific Aim 1 will provide core facilities for investigators to carry out metabolic flux experiments, utilizing our expertise in stable isotope tracers and mass spectrometry. Aim 2 will conduct analyses of murine tissues and body fluids provided by investigators carrying out metabolic studies. This includes investigators working at CWRU and in other institutions, domestic and globally. In Aim 3 we will develop additional innovative tracer and methodological approaches for assessing oxidative stress and inflammation. This involves a new “sub-core” that will also provide custom synthesis of stable isotopic tracers and mass spectrometric analysis of lipid peroxidation products. In Aim 4 we will provide training and education to investigators and their staff for, (i) proficiency in the use of isotopes for metabolic studies, (ii) understanding the capabilities of the MMPC and designing appropriate experiments for their questions, (iii) carrying out procedures in their laboratory for preparing samples to be analyzed by the MMPC, and/or (iv) learning to carrying out the complete procedure in their own laboratories. The implementation of these aims is expected to significantly advance the field of metabolism and assist investigators in Cleveland, nationally and globally, to discover new pathways and mechanisms that cause diabetes and obesity- related chronic diseases.

抽象的 Case-MMPC 的使命是促进小鼠的表型表征 研究代谢疾病的研究人员，重点关注糖尿病和 肥胖。我们在 MMPC 联盟内开展工作，以补充和部分重叠 其他六个中心的活动。我们的利基是代谢的测量和解释 借助稳定同位素示踪技术和质量的通量和代谢组模式 光谱测定法，重点是避免经常困扰此类协议的伪影。这 代谢组学和稳定同位素技术的结合可以发现新的 途径和新的监管机制。这种方法是 Case-MMPC 首创的 并从此赢得了世界各地研究人员的青睐。我们中心还 有助于开发 NIDDK 赞助的“同位素用途”年度课程 代谢研究”，将于 2015 年 11 月由 11 名教员讲授第 8 次 MMPC 和美国大学，并吸引了国际人士参加。案例-MMPC是 目前已进入运营第九年。此应用程序请求支持增加 中心的能力，扩大提供的示踪剂和测量的代谢物的种类 包括氧化应激和炎症相关途径。具体目标 1 将提供核心 为研究人员提供利用我们在稳定方面的专业知识进行代谢流实验的设施 同位素示踪剂和质谱分析。目标 2 将进行小鼠组织和身体的分析 进行代谢研究的研究人员提供的液体。这包括调查人员 在 CWRU 以及国内和全球其他机构工作。在目标 3 中，我们将开发 用于评估氧化应激的其他创新示踪剂和方法学方法 炎。这涉及一个新的“子核心”，它还将提供稳定的定制合成 脂质过氧化产物的同位素示踪剂和质谱分析。在目标 4 中，我们将 为调查人员及其工作人员提供以下方面的培训和教育：(i) 熟练使用 用于代谢研究的同位素，(ii) 了解 MMPC 的功能并设计 针对他们的问题进行适当的实验，（iii）在他们的实验室中执行程序 准备供 MMPC 分析的样本，和/或 (iv) 学习执行 完整的程序在自己的实验室进行。这些目标的实现预计将 显着推进新陈代谢领域并协助克利夫兰的研究人员，全国 在全球范围内，发现导致糖尿病和肥胖的新途径和机制- 相关慢性疾病。