Objective Research objectives and content We have shown that H. pylori, a major aetiological agent in the development of gastrointestinal disseases, induces reduction of the transepithelial resistance of epithelial monolayers in a process involving increased paracellular permeability, suggesting that the bacteria alters the normal tight junction function. These preliminary studies also suggested the ocurrence of specific bacterial antigen-cellular receptor interaction followed by intracellular signaling. Aim 1. Analysis of cellular mechanisms mediating H. pylori induced altered permeability in the epithelium. Density and distribution of the tight junction proteins Z0-1 y Z0-2 will be assessed by immunohistochemical and microscopical techniques using computerized image analysis as well as analysis of specific H. pylori-induced phosphorylation of Z0-1 and Z0-2 and others. Variations on the intracellular calcium concentration will be determined and protein sequencing will be also carried out. Aim 2. Characterization of H. pylori protein(s) involved in alteration epithelial paracellular permeability. Identification, purification, identification of target gene and subcloning and expresion in E. coli will be carried out. Polyclonal antibodies to H. pylori antigens will be generated. If possible receptor cross-linking studies will be carried out to identify surface receptors for candidate proteins on epithelial cells. Training content (objective, benefit and expected impact) The proposed study is expected to identify proteins of major interest which may be of importance in determining the immune response of the host to H. pylori infections. Hence, proteins identified in this study could well become candidates either for immune manipulation of the gastrointestinal tract or as vaccines. Therefore there should be considerable commercial interest in this particular field of study. Links with industry / industrial relevance (22) Dermot Kelleher, scientist in charge at the host institution, is a Wellcome Senior Fellow in Clinical Science. Fields of science natural sciencesbiological sciencesmicrobiologybacteriologynatural scienceschemical sciencesinorganic chemistryalkaline earth metalsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunologymedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines Programme(s) FP4-TMR - Specific research and technological development programme in the field of the training and mobility of researchers, 1994-1998 Topic(s) 0302 - Post-doctoral research training grants TL02 - Molecular Biology and Biochemistry Call for proposal Data not available Funding Scheme RGI - Research grants (individual fellowships) Coordinator THE PROVOST, FELLOWS AND SCHOLARS OF THE COLLEGE OF THE HOLY AND UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN HEREINAFTER TRINITY COLLEGE DUBLIN EU contribution No data Address James Street 8 Dublin Ireland See on map Total cost No data Participants (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all Not available Spain EU contribution No data Address See on map Total cost No data