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 病例MMPC的任务是促进小鼠的表型表征 研究代谢疾病的研究人员重点是糖尿病和优先考虑 肥胖。我们在MMPC财团内工作，以完成并部分重叠 其他六个中心的活动。我们的利基是代谢的测量和解释 通过稳定的同位素示踪技术和质量的帮助，通量和代谢组模式 光谱法，重点是避免经常困扰这种协议的人工制品。这 代谢组学和稳定同位素技术的组合允许发现新的 途径和新的监管机制。这种方法是在Case-MMPC上开创的 此后，世界各地的调查人员都受到青睐。我们的中心也是 在NIDDK赞助的年度课程的开发中发挥了作用 代谢研究”，该研究将在2015年11月的第8次由11次教授 MMPC和美国大学，并吸引了国际出席。 case-mmpc是 目前正处于运营的第9年。本申请要求支持增加 中心的容量，扩大了所提供的示踪剂的曲目和所测量的代谢 包括氧化应激和炎症相关途径。特定目标1将提供核心 调查人员使用我们的专业知识来进行代谢通量实验的设施 同位素示踪剂和质谱。 AIM 2将对鼠组织和身体进行分析 进行代谢研究的研究人员提供的流体。这包括调查人员 在CWRU和其他机构（国内和全球）工作。在目标3中，我们将发展 其他创新的示踪剂和方法论方法，用于评估氧化应激和 炎。这涉及一个新的“子核”，还将提供稳定的自定义合成 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 向调查人员及其员工提供培训和教育，以供（i）熟练使用 代谢研究的同位素，（ii）了解MMPC的功能和设计 针对他们的问题进行适当的实验，（iii）在其实验室中执行程序 准备通过MMPC分析的样品和/或（iv）学习执行 在自己的实验室中完成程序。这些目标的实施将有望 显着发展新陈代谢领域，并协助克利夫兰的调查人员 在全球范围内，发现引起糖尿病和肥胖症的新途径和机制 相关的慢性疾病。