Biomedical Cores complement the research interests of the CSIBD investigators and promote research in areas of recognized priority in advancing the understanding of IBD.
The major roles of the Genetics, Genomics and Molecular Biology (GGMB) Core are 1) to provide services in the utilization of advanced genetics and molecular biological techniques and 2) to facilitate the implementation of advances in genomics and molecular biology to IBD research. Application of genetics and molecular biological approaches is central to the evaluation of processes underlying the development of IBD according to the hypotheses that serve as a foundation for this center. As genetics play a significant role in determining the risk of developing IBD, identifying specific risk-associated genes is a priority for CSIBD researchers who are seeking to determine underlying disease processes. This core principally provides access to high-demand, mission-enabling tools for the investigator cohort participating in the CSIBD. The core also provides access to capital or resource-intensive methodologies, such as laboratory automation cDNA and siRNA libraries, and BAC-centered recombinant DNA techniques. The importance of molecular methods for the understanding of mechanisms of immunity and generating transgenic/knockout mice is undeniable, and their impact and dissemination throughout biological disciplines grow every year. 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, and expression of reporter genes and proteins to allow cellular localization and physiological analysis. For those laboratories with limited expertise in molecular biology, the core has developed a major educational effort consisting of the annual current techniques course in molecular genetics and training in genetic epidemiology, quantitative biology, and genomic medicine.
The Morphology Core facilitates the provision of sophisticated morphologic correlation with molecular studies that would not otherwise be available to many CSIBD investigators. It is an underlying premise of this core that understanding the pathophysiologic importance of factors and processes identified by molecular biological and other approaches is dependent on the assessment of morphologic changes in mucosa and more refined analysis of protein localization. This evaluation is especially critical for the study of murine models of IBD in which any manipulation or evaluation of markers/inflammatory mediators must be judged against the yardstick of mucosal inflammation.
The Clinical/Tissue Core was developed as a resource for providing carefully collected, catalogued and shared samples from “pedigreed” patients for investigators in this center, thus facilitating the translation of research. These samples include tissue and blood (serum and DNA) from IBD patients and controls. In addition, through the IBD Patient Registry, the core provides ready access to individual patients and populations for basic studies of IBD as well as patients for studies examining disease mechanisms in vivo. An important ancillary role of this core is to create a “gold standard” collection of these materials that serves as a reference standard for scientists nationally. Although the core was not initially conceived to serve as a mechanism to organize clinical therapeutic trials, but to facilitate the study of mechanisms of disease, it has provided an engine for patient-oriented as well as translational IBD research.
The Immunology Core was developed to increase the effectiveness and interaction of the large number of CSIBD scientists exploring immune function, as well as to augment the power of molecular studies in defining functional features of the immune system. One corollary of the central hypothesis of the CSIBD is that IBD results from failure of down-regulation of immune and inflammatory responses, due to genetically or environmentally determined events. The fundamental importance of immune processes in the pathogenesis of IBD warrants an interest in facilitating research in these areas.
The Genetic Animal Model Core was initially developed to facilitate the use of informative animal models of chronic colitis. Murine models of intestinal inflammation arising from a number of genetic manipulations offer the most direct means to approach the underlying hypothesis of the CSIBD, i.e. characterization of the effects of genetic factors in altering mucosal barrier function and immune responses that lead to chronic inflammation. These models also allow the opportunity to define the importance of interaction among different genetic loci and the impact of environmental factors on phenotypic expression of IBD. As a result of these developments, this core places a major emphasis on these valuable research tools, providing economical access to these models by CSIBD investigators and promoting further characterization of these models.