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.
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