Core Center for Musculoskeletal Research

这次重新提交的目的是利用功能性对骨骼生物学的影响。科学基地被选定为一组互补性的研究者，他们相互激励，相互学习。核心的主题是使用原代细胞和完整动物分析对骨骼发育和维持重要的基因和细胞。之所以做出这样的选择，是因为我们坚信，生物相关的细胞生物学和基因调控必须在完整骨骼的背景下进行研究，特别是在应用于小鼠诱变计划时，这将成为功能基因组学的基础。对于科学基地的许多成员来说，矿石中所代表的技能并不是当前研究计划的一部分。相反，核心课程旨在向我们的研究人员介绍可以应用于他们研究问题的新概念、技术和分析方法。功能基因组学和定量生物学正在重新定义其他生物学学科，该中心的拨款旨在使我们的研究人员能够评估这些新方向。因此，所提出的载体核心的功能是制造逆转录载体构建体和产生细胞，将基因导入原代细胞。此外，该核心将有助于构建用于产生转基因或基因敲除小鼠的构建物。成像核心的设计目的是为科学基地所做的许多生物观察提供定量。这将包括在完整骨或原代骨细胞培养中显示GFP表达的细胞的定量组织学测量和FACS分析。此外，骨和关节的结构特征将通过muCT分析进行量化。微阵列核心将开发适合骨骼生物学的基因集，并为杂交提供基因阵列和设施。信息学小组将为这类实验的分析提供指导，并开发结合骨骼生物学原理的新计算方法。行政中心将制定一个强有力的教育和增强计划，以帮助研究基地认识到这些新方法的力量，并协助将这些计划融入他们的研究计划。试点和可行性计划是针对新的初级教师，以帮助他们过渡到独立，并影响他们的研究课题的选择，包括骨骼生物学相关的问题。我们非常幸运地与医学院和牙科学院建立了一个非常支持的行政结构，以招募新的教师和购买新的技术，这将使我们的骨骼生物学项目在规模和复杂性上得到发展。

This resubmission is designed to take advantage of the impact that functional will have on skeletal biology. The scientific base was selected to be a group of complementary investigators motivated to interact and learn from each other. The theme of the core is the analysis of genes and cells important to the development and maintenance of the skeleton using primary cells and intact animals. This choice has been made because of the strong belief that biologically relevant cell biology and gene regulation has to be studied in the context of the intact skeleton particularly when applied to the mouse mutagenesis programs that will become the foundation for functional genomics. For many members of the scientific base, the skills represented within the ores are not part of the current research program. Instead the cores are designed to introduce our investigators to new concepts, technologies, analytical approaches that can be applied to their research questions. Functional genomics and quantitative biology is redefining other biological disciplines and this center grant is designed to make these new directions assessable to our investigators. Thus the function of the proposed vector core is to make retrovector constructs and producer cells to introduce genes into primary cells. In addition this core will assist in making constructs that will be used to generate transgenic or knockout mice. The imaging core is designed to provide quantitation to many of the biological observations made by the scientific base. This will include quantitative histological measurements and FACS analysis of cells exhibiting GFP expression within intact bone or primary bone cell culture. In addition, the structural characteristics of bone and joints will be quantitated with muCT analysis. The microarray core will develop gene sets appropriate for skeletal biology and provide the gene arrays and facilities for the hybridization. An informatics group will provide direction in the analysis of this type of experiment and develop new computational approaches that incorporate principles of skeletal biology. The administrative core will develop a strong educational and enhancement program to help the research base appreciate the power of these new approaches and assist the assimilation of these programs into their research program. The pilot and feasibility program is directed at new junior faculty to assist their transition toward independence and to influence there choice of research topics to include problems related to skeletal biology. We have been extremely fortunate to have a very supportive administrative structure with the Medical and Dental Schools to recruit new faculty and purchase new technology that will allow our skeletal biology programs to grow in size and sophistication.