One of the notable strengths of this Morphology Core is the broad range of morphological and Immunolocallzatlon techniques offered. A combination of techniques provides a complete spectrum of analysis progressing from the light microscopic level to the electron microscopic level for both morphological and immunocytochemlcal studies. Most recently, real time live cell imaging, total Internal reflection microscopy and laser cutting microdissection have been added to the core repertoire. These techniques allow Immunofluorescence and immunoperoxidase localization on whole cell monolayers, thin frozen sections of cells, tissues and Isolated membranes and vesicles. Techniques Include conventional, electron and confocal microscopy, localization on polarized cells, immunocytochemlcal localization at the ultrastructural level by immunoperoxidase and immunogold staining on Epon and Lowicryl embedded sections of tissue and cells (Including biopsy material), ultrathln frozen sections which allow the co-localization of pairs of proteins and TUNEL assay to study apoptosis. Through this core facility, CSIBD investigators have the opportunity to explore several different methods for observing the ultrastructural morphology of cells and tissues and for localizing proteins in these specimens. Over the previous funding period, investigators have used our Perkin-Elmer Live Cell Imager, a spinning disk confocal microscope to analyze cellular events as they occur In real time. By making these techniques available to investigators whose expertise lies in other areas, the Morphology Core serves to encourage a multi-disciplinary approach to the study of Intestinal disease. Studies supported by the Morphology Core during the current support period have resulted In 122 original publications in peer-reviewed journals listed at the end of the description of this core. Since the formation of the center. Dr. AtuI K. Bhan has served as Core Director, a role in which he will continue throughout the renewal period. Dr. Dennis Brown, Co-Director, an Internationally recognized expert in morphologic approaches to the study of epithelial cells, Is responsible for electron and confocal microscopy and related services of the core. The recent addition of Dr. Yukako Yagi who directs the Advanced Pathology Imaging Laboratory to the Morphology Core as an Associate Core Director, has added another dimension to the Core of providing sophisticated digital technology for the Center investigators. The core technicians are highly experienced microscopists and can frequently help Investigators without the Intervention of the Core Directors. With the expertise In operation and management of the Morphology Core over the past 18 years and the continuous molding of the Core In response to the evolving needs of the increasing base of CSIBD Investigators, evolutionary modifications in the services provided by the Core have been made and more are planned (See below). As a result of increased need for preparation of H&E stained paraffin-embedded sections of tissues for histology and pathology, as well as immunohistochemical studies on frozen tissue sections, greater resources will be directed to these services. Indeed, two new Leica cryostats were purchased three years ago to address this issue. This increased need resulted from the growing use of murine models of IBD established through gene deletion, mice made available through the Genetic Animal Model Core (e.g., the laboratories of Drs. Bhan, Atsushl Mizoguchi, Avruch, Terhorst, Snapper, Lacy-Hulbert, Nanthakumar, Xavier and others) and the development of a variety of transgenic mouse lines to explore IBD-related factors and processes, especially with the Implementation of a transgenic mouse service by the Molecular Biology Core during the current support period.