This is a revised application for continued support of a programmatic, multi-disciplinary project aimed at investigating the regulation and adaptation of gastrointestinal (GI) function. The objectives of the first project (P.I.: G.A. Castro) are to further our understanding of how the mucosal immune system regulates epithelial cell and smooth muscle functions in the gastrointestinal tract and its role in physiological adaptations and maladaptations. The objectives of the second project (P.I.: Mari K. Haddox) are to elucidate the biochemical and molecular mechanisms responsible for expression and regulation of ornithine decarboxylase activity in gastrointestinal epithelia. The third project (P.I.: L.R. Johnson) is a logical extension of the P.I.'s efforts during the past five years to elucidate the roles of ornithine decarboxylase and polyamines in cell division, cell migration and cell-substrate interactions that are essential for the healing processes in response to mucosal damage. All of these projects will require the continued use of the Computational Core (C) supported by our current PPG Award and extensive use of a newly-established Cytobiology Core (B); the Administrative Core (A) will provide secretarial services and financial management for the research projects and scientific cores. The proposed studies involve a multidisciplinary approach aimed at resolving important questions at the molecular, cellular, tissue and organ levels. The unifying theme of these studies is to further our understanding of how the gastrointestinal tract adapts to environmental stresses in an integrative fashion.
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