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

间充质和代谢神经调节的生理学核心的长远目标 Network Cobre(PC-MN)旨在提供高质量的组织、细胞和体内表型鉴定服务 对于缅因州医学中心科布雷研究所的科学家和其他内部调查人员，以及 与外部调查人员共享资源。建议的PC-MN建立在这样的前提下，即为了 阐明哺乳动物代谢的基本动态平衡机制，必须有一个 常备核心提供表型服务以及智力资源，以指导调查人员- 启动了研究。为了实现这一目标，PC-MN将成为全身研究的“家” 以及科布雷每个拟议项目的组织表型。提出了四个具体目标： 首先，PC-MN将整合之前在生理学核心中开发的基础设施(作为一部分 干细胞眼镜蛇)，然后在目前的眼镜蛇扩大体内表型的服务 项目。我们将为研究人员提供一系列全面的血液学生化分析， 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、食物消费、体力活动)，并扩大服务。这将是 包括额外的新陈代谢笼子，安置在温度控制室中，核心为遥测 体温分析，增强了热成像功能，以及活体核磁共振和DXA。 其次，PC-MN将通过测量提供先进的细胞和线粒体生物能量学 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， 内脏和腹股沟白色脂肪组织、棕色脂肪组织、新生儿跖骨和头盖骨) 和线粒体。第三，PC-MN将指导研究人员确定最佳实验 设计并分析突变菌株的代谢谱、总组织质量和部分组织质量、能量 费用、生化标记物和底物利用率。第四，PC-MN将保持 最高的质量控制，同时制定每年评估服务的指标。我们将继续 定义并重新评估成本结构，包括针对非Cobre用户的退款费用，以确保 PC-MN将能够通过新的方法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和 与此Cobre中的四个项目的集成将使个人调查人员受益，因为它提供了 为他们提议的项目和规划未来的R01应用程序提供高质量的数据集。 来自这些基础研究和转译研究的见解最终可能应用于临床试验 患有骨质疏松症和肥胖症的人。

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.!