Core Center for Musculoskeletal Research

这次重新提交的目的是利用功能将对骨骼生物学产生的影响。科学基地被选为一组互为补充的调查员，他们的动机是相互交流和学习。核心的主题是利用原代细胞和完整的动物分析对骨骼的发育和维护至关重要的基因和细胞。之所以做出这一选择，是因为人们坚信，必须在完整骨骼的背景下研究与生物相关的细胞生物学和基因调控，特别是当应用于小鼠突变计划时，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，这些核心的设计是为了向我们的研究人员介绍可以应用于他们的研究问题的新概念、技术和分析方法。功能基因组学和数量生物学正在重新定义其他生物学学科，这项中心拨款的目的是使我们的研究人员能够评估这些新的方向。因此，所提出的载体核心的功能是构建逆转录载体并产生细胞，以将基因导入原代细胞。此外，这个核心将帮助构建用于产生转基因或基因敲除小鼠的结构。成像核心的设计是为了对科学基地进行的许多生物观测提供量化。这将包括对完整骨或原代骨细胞培养中显示GFP表达的细胞进行定量组织学测量和FACS分析。此外，骨和关节的结构特征将通过MULT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。一个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。管理核心将开发一个强大的教育和增强计划，以帮助研究基地认识到这些新方法的力量，并帮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员，以帮助他们向独立的过渡，并影响他们的研究主题的选择，包括与骨骼生物学有关的问题。我们非常幸运地拥有一个非常支持医学院和牙科学校的管理结构，可以招聘新的教员并购买新的技术，这将使我们的骨骼生物学项目的规模和复杂性不断扩大。

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.