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

代谢的间质和神经调节生理学核心的长期目标 网络COBRE（PC-MN）是提供高质量的组织，细胞，和在体内表型服务 为缅因州医学中心研究所COBRE科学家和其他内部调查人员， 与外部调查人员共享资源。所提出的PC-MN是建立在这样的前提下的， 为了阐明哺乳动物体内代谢的基本稳态机制， 常设核心提供表型分析服务以及智力资源，以指导研究者- 发起的研究。为了实现这一目标，PC-MN将成为整个身体的调查“家” 和组织表型分析。提出了四个具体目标： 首先，PC-MN将整合先前在生理学核心中开发的基础设施（作为 的干细胞COBRE），然后在目前的COBRE中扩展体内表型分析服务 项目我们将为研究人员提供一系列生化检测， 代谢和骨骼表型。我们将进行动态代谢表型分析（例如能量 支出、食物消耗、体力活动），并扩大服务。这将 包括容纳在温控室中附加代谢笼，其中遥测用于核心 体温分析，通过热成像能力增强，以及体内NMR和DXA。 其次，PC-MN将通过测量细胞和线粒体的能量， 细胞中的氧化磷酸化和糖酵解，选择性组织（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、新生儿跖骨和颅骨） 和线粒体。第三，PC-MN将为研究者提供咨询，以确定最佳实验方案。 设计，然后分析突变株的代谢谱，总组织质量和部分组织质量，能量 消耗、生化标记和底物利用。第四，PC-MN将保持 最高的质量控制，同时制定指标，每年评估服务。我们将不断 定义并重新评估成本结构，包括非COBRE用户的退款费用，以确保 PC-MN将能够支持服务的进一步扩展， 同事和合作的科学家。成功扩展生理学核心服务， 与本COBRE中的四个项目的集成将通过提供 高质量的数据集，用于他们建议的项目和规划未来的R 01应用。 这些基础和转化研究的见解最终可以应用于临床试验 骨质疏松症和肥胖症的患者

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.!