The goal of this program is to examine the physiological responses of proteins in several gastrointestinal tissues at the cellular and molecular level under common environmental conditions (developmental, dietary, inflammatory, and metabolic or hormonal). Some projects will study proteins produced by cells of ectodermal origin (enterocyte, chief cells of stomach, pancreatic exocrine cells); some will study proteins secreted by inflammatory cells in the intestinal mucosa. Proteins to be studied include apolipoproteins (project 1), entercoyte brush border and basolateral membrane protein (project 2), maltase-glucoamylase (project 3), immunoglobulius (project 4), cobalamin binding proteins (project 5), and pancreatic lipase and colipase (project 6). The techniques used will be derived from molecular biology (projects 1,3,5), cell biology (projects 1,2,6), and immunology (projects 4,6). These studies require facilities which can be conveniently shared, and include HPLC (for peptide and lipid separations), protein sequenators, oligodeoxynucleotide synthesizer, cell culture of lymphocytes, intestinal (e.g. CaCo2) and hepatic (HepG2) cell lines, and light and electron microscopy for morphology, immune localization, and in situ hybridization. The project will allow the formation of three core facilities (biomolecular analysis, morphology, and cell culture) which will be dedicated to carrying out research on gastrointestinal physiology at the cellular and molecular levels. These studies will provide insight into 1) the mechanism of cellular responses of gastrointestinal tissues to environmental changes, 2) the molecular mechanisms of gut differentiation, 3) the synthesis and processing of cellular and secreted gastrointestinal proteins, and 4) the biochemical changes in three human disorders, sucrase- isomaltase deficiency (project 3), pernicious anemia (project 5), and pancreatic insufficiency (project 6).