The importance of molecular methods for the understanding of mechanisms of innate, adaptive immunity barrier function and generating transgenic/knockout mice is undeniable, and their impact, and dissemination throughout the biological disciplines, grows every year. Molecular techniques have contributed to many of the most recent advances in the identification of the cellular circuits that control innate immune responses, lymphocyte activation, the network of cells that maintain intestinal homeostasis and the eliciting factors inducing the Immunological programs responsible for intestinal inflammation in IBD. As important and powerful as the methodological advances have been, they have led to an only partial unraveling of the complex and redundant regulatory circuitry that underlies the impaired physiology of Crohn's disease and Ulcerative colitis. It is also apparent from the description of the CSIBD research base that most center investigators use basic molecular biological techniques as a fundamental component of their research projects. These techniques permit the identification and characterization of genes regulating epithelial and immune cell function, analysis of the expression of these genes, determination of the functions and interactions of the encoded proteins, expression of reporter genes and proteins to allow cellular localization and physiological analysis. The GGMB Core provides cost-effective sen/ices and reagents, as well as broad-based, rigorous training programs. In addition, it offers numerous opportunities for technology transfer. In the coming 5 year period, our goals will be to facilitate the appropriate and effective use of selected newer technologies, including RNA interference, high throughput sequencing, gene expression analysis, functional annotation of genetic factors associated with IBD risk and enable access to platforms at the Broad Institute. In the last funding period the core in collaboration with Center for Computational and Integrative Biology has purchased 20,000 unique full length human cDNA clones and is in the process transferring full length inserts into epitope tagged vectors. Additional features include a fully validated PCR primer sets for all human and mouse genes. Selected other specialized reagents, including differentiated epithelial and immune cell lines, hybrid lines for chromosome localization and predivided library pools for eukaryotic expression screening are included among core reagents available to CSIBD investigators. The core maintains a computer cluster and has developed Bioinformatics analysis tools for genetics, genomics and high throughput data analysis. The core will provide increased access to and training In the use of bioinformatics analysis and software, including the large variety of databases and software tools available via the internet, as well as molecular biology and statistical applications acquired by the GGMB Core and made available to center investigators through the shared intranet. We will continue support for DNA microarray analysis begun during the current funding period that facilitated the productive and cost-effective use of this technology by IBD investigators. Studies conducted by CSIBD investigators have generated several important new insights into immune cell function, epithelial cell biology and intracellular signaling. A new service to be provided by the GGMB Core during the next funding period will be to facilitate access to state of the art platfomis at the Broad Institute at MIT and Harvard.
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