Core D: Physiology Core for the Mesenchymal and Neural Regulation of Metabolic Networks (PC-MN)

核心 D：代谢网络间充质和神经调节的生理学核心 (PC-MN)

• 批准号: 10246813
• 负责人: CLIFFORD JAMES ROSEN
• 金额: $ 26.5万
• 依托单位: MAINEHEALTH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10246813
• 关键词: 3-Dimensional; Adipocytes; Adipose tissue; Algorithms; Animal Model; Back; Biochemical; Biochemical Markers; Biochemical Pathway; Bioenergetics; Biological Assay; Biological Markers; Body Composition; Body Temperature; Books; Brown Fat; Cell Culture Techniques; Cells; Centers of Research Excellence; Charge; Clinical Trials; Counseling; Country; Data Set; Dual-Energy X-Ray Absorptiometry; Energy Metabolism; Experimental Designs; Fees; Future; Generations; Genetic Transcription; Genus Hippocampus; Glycolysis; Goals; Hematology; Home; In Vitro; Individual; Infrastructure; Institutes; Institution; Israel; Maine; Mammals; Measurement; Measures; Medical center; Mesenchymal; Metabolic; Metabolism; Metatarsal bone structure; Methodology; Mitochondria; Monitor; National Institute of General Medical Sciences; Neonatal; New England; Obesity; Osmium; Osteoporosis; Oxidative Phosphorylation; PC3 cell line; Phenotype; Physical activity; Physiology; Principal Investigator; Quality Control; Research Institute; Research Personnel; Resource Sharing; Resources; Scientist; Serum; Services; Site; Structure; Telemetry; Temperature; The Jackson Laboratory; Tissues; Training; Universities; Virginia; Visceral; cost; cost effective; experience; food consumption; graduate student; imaging capabilities; in vivo; insight; meetings; metabolic abnormality assessment; metabolic phenotype; microCT; mutant; neuroregulation; novel; service utilization; skeletal; soft tissue; stem cells; tissue culture; tissue respiration; translational study

The long-term goal of the Physiology Core for the Mesenchymal and Neural Regulation of Metabolic Networks COBRE (PC-MN) is to provide high quality tissue, cellular, and in vivo phenotyping services for Maine Medical Center Research Institute COBRE scientists and other internal investigators, and to share resources with outside investigators. The proposed PC-MN is built on the premise that in order to elucidate the fundamental homeostatic mechanisms of metabolism in the mammal, there must be a standing Core to offer phenotyping services as well as intellectual resources to guide investigator- initiated studies. To achieve this goal, the PC-MN will become the investigative `home' for whole body and tissue phenotyping for each proposed project in the COBRE. Four specific aims are proposed: First, the PC-MN will integrate the infrastructure previously developed in the Physiology Core (as part of the Stem Cell COBRE) and then expand services for in vivo phenotyping in the current COBRE projects. We will offer an array of biochemical assays for investigators for comprehensive hematologic, metabolic and skeletal phenotyping. We will perform dynamic metabolic phenotyping (e.g. energy expenditure, food consumption, physical activity) in animal models and expand services. This will include additional metabolic cages housed in a temperature-controlled chamber, with telemetry for core body temperature analysis, augmented by thermal imaging capabilities, and in vivo NMR and DXA. Second, the PC-MN will provide advanced cellular and mitochondrial bioenergetics by measuring oxidative phosphorylation and glycolysis in cells, selective tissues (e.g. 3D adipose cell cultures in vitro, visceral and inguinal white adipose tissue, brown adipose tissue, neonatal metatarsals, and calvariae) and mitochondria. Third, the PC-MN will counsel investigators in defining the optimal experimental design and then analyzing metabolic profiling of mutant strains, total and fractional tissue mass, energy expenditure, biochemical markers and substrate utilization. Fourth, the PC-MN will maintain the highest quality control while instituting metrics to assess services on a yearly basis. We will continually define and re-evaluate cost structures including charge-back fees for non-COBRE users to insure that the PC-MN will be able to support further expansion of services with new methodologies from colleagues and collaborating scientists. Successful expansion of Physiology Core services and integration with four projects in this COBRE will benefit individual investigators by providing high quality data sets for their proposed projects and for planning future R01 applications. Insights from these basic and translational studies could ultimately be applied in clinical trials of individuals with osteoporosis and obesity.!

生理学核心的长期目标是代谢的间充质和神经调节 Networks Cobre（PC-MN）提供高质量的组织，细胞和体内表型服务 用于缅因州医学中心研究所的鞋垫科学家和其他内部研究人员，以及 与外部调查人员共享资源。拟议的PC-MN建立在以下前提下 阐明哺乳动物中代谢的基本稳态机制，必须有一个 提供表型服务以及智力资源来指导研究者 - 开始研究。为了实现这一目标，PC-MN将成为整个身体的调查“家” 和毛绒中每个提议的项目的组织表型。提出了四个具体目标： 首先，PC-MN将整合以前在生理核心中开发的基础架构（作为一部分 干细胞毛囊），然后扩展当前毛病中体内表型的服务 项目。我们将为研究人员提供一系列的生化测定，以供综合血液学， 代谢和骨骼表型。我们将执行动态代谢表型（例如能量 动物模型中的支出，食物消费，体育活动）并扩大服务。这会 包括安装在温度控制室内的其他代谢笼，并带有用于核心的遥测 体温分析，通过热成像功能增强，体内NMR和DXA。 其次，PC-MN将通过测量来提供先进的细胞和线粒体生物能力 细胞，选择性组织中的氧化磷酸化和糖酵解（例如，体外3D脂肪细胞培养物， 内脏和腹股沟白色脂肪组织，棕色脂肪组织，新生儿质子组织和钙） 和线粒体。第三，PC-MN将咨询调查人员定义最佳实验 设计，然后分析突变菌株，总和分数质量的代谢分析，能量 支出，生化标记和底物利用率。第四，PC-MN将保持 最高质量控制的同时，在每年制定指标以评估服务。我们将不断 定义和重新评估成本结构，包括无需用户的收费费用，以确保该费用 PC-MN将能够通过来自 同事和合作科学家。成功扩展生理核心服务和 与此毛绒中的四个项目集成将使个人调查人员提供受益 其拟议项目和计划未来R01应用程序的高质量数据集。 这些基本和转化研究的见解最终可以应用于临床试验 患有骨质疏松和肥胖的人。