A. History and Evolution of the Core The mission of the Center for Gastrointestinal Biology and Disease is to promote and enhance multidisciplinary digestive disease research. The Center achieves this mission, in part, through core laboratories that provide training, technical support or laboratory services to researchers. The directors and the mission of the Histology and Imaging Core have changed over time in response to changes in the research needs and interests of Center members, but our commitment to providing cutting edge services for the benefit of our members has remained constant. The Histology and Imaging Core represents the evolution of a Molecular Biology Core that has been one of the CGIBD cores since 1989. When first conceived, the purpose of the molecular core was to provide services and training in molecular biology techniques. The core initially consisted of a basic recombinant DNA unit and a transgenic mouse development unit. The basic recombinant DNA unit provided core reagents, protocols, training and assistance for investigators with limited experience. The transgenic mouse unit (shared with other groups on campus) provided mouse models with over-expression or deletion of targeted genes for analyses of effects on gastrointestinal function. In 1993, the core added a Molecular Morphology unit that was designed to provide hands-on training, facilities and space for in situ hybridization histochemistry. The unit provided reagents and protocols for immunohistochemistry and staining, as well as state of the art image analysis facilities for analyzing molecular morphology data and for photographing and preparing data for publication and presentation. The expertise and needs of Center members evolved over time, and new technology became available. In order to reflect emphasis on microscopy and in-situ hybridization, the core was renamed the Molecular Imaging Core. Dr. John J. Lemasters, an expert in confocal microscopy, served as core director. The core offered a state-of-the-art confocal imaging facility for high resolution 3-dimensional optical imaging of thick cells and tissues, a histology laboratory to provide high quality histological services, a digital darkroom where image data could be analyzed, processed and prepared for presentation in a wide variety of formats, and a consultation service. Dr. Lemasters was the heaviest user and the director of the confocal facility. When he left the University in 2006, we replaced confocal imaging and the digital darkroom with mouse endoscopy with the approval of NIDDK DDRCC Program Director Judith Podskalny. Investigators in need of confocal services were able to obtain these services elsewhere on our campus. In this renewal application we propose to subsidize confocal services which are important to the research of several of our members. We propose a new name for the Core - the Histology and Imaging Core. As described in the pages that follow, the core will provide: histology services (including immunohistochemisty, digital scanning and image analysis), confocal microscopy support, and mouse endoscopy. B. Justification The Histology Component of the Core eliminates duplication of effort and resources (and their associated costs) for individual CGIBD investigators. The professional core staff provides high quality data, consistency and reduced costs. Services from the Histology Component cost far less than commercial sources. The digital scanning and image analysis make it possible to easily duplicate and share images and to use software to score images. Confocal microscopy is essential to the research of several of our investigators. Use of this technology grew markedly during the previous funding period and is expected to increase. In order to support this research the CGIBD will subsidize confocal use. Mouse endoscopy is an important diagnostic component in the early detection, documentation of tumor progression and comparison of different tumor types (polypoid and flat tumors;see figure 1 and 2) as well as colonic inflammation. Using this equipment we have been able to follow individual mice for up to 8 months with sequential mouse endoscopies. In our hands murine endoscopy has been proven safe, reliable and reproducible. We use isoflurane (2-3%) as an anesthetic agent and have not encountered significant side effects (perforation, death of mice during or after the procedure). Of note, employing mouse endoscopies, especially in experiments using mouse tumor models and mouse models of colitis, can prevent necropsies of a large number of mice. Thus the service of performing murine endoscopies serves animal welfare and significantly reduces animal numbers needed to gain significant results.
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