Walsh Fellowship Number – 2014058 Duration – 4 year PhD Title: Changing the barrier to infection: modulation of the mucosal glycome using dairy-derived ingredients Abstract: Nutritional intake may influence most organs, but it is the epithelium of the gastrointestinal tract that has the most prolonged exposure to minimally digested components, and accordingly, the most significant response to variations in nutrient intake. In humans, the epithelial surface glycans create a landscape of recognition sites, barriers and carriers which control immunological recognition, cell-cell adhesion and pathogen attack. Evidence is emerging that mucosal glycosylation in particular can alter in response to nutrition, and this may be an important mechanism for regulating the supramucosal microbiome to prevent colonisation or penetration by pathogens. As the sole source of exogenous material, the provision of breast milk and indeed formula to the neonate has considerable implications in the development of the infant intestinal epithelium. Research from our group and others now suggests that components in bovine milk can modulate the expression of intestinal epithelial cell surface glycans, which are both potential targets for microbial adhesion, or microbial energy sources that may influence population dynamics. This phenomenon occurs either by modulating glycan expression and/or the expression of modifying enzymes. The objective of this study is to examine, in vitro initially, the effect of various dairy-derived ingredients (skim milk, sweet whey, colostrum, whey permeate, demineralised whey powder and oligosaccharide-enriched powder) on surface glycosylation of epithelial cells and to what extent pathogen interaction is modulated. This work will utilise colonisation models and lectin arrays already established between Teagasc, UCD and NUIG as part of the Alimentary Glycoscience Research Cluster (AGRC). The results will be validated in vivo using a neonatal rat model which will be done collaboration with the University of California, San Diego. Specific changes in N- and O-linked glycosylation will be determined through collaboration with the glycoscience group at UCD. It is hoped this study will not only expand the potential of milk components as functional food ingredients but also enhance our knowledge on how pathogens interact with host cells. Ascertaining the nature of the interactions between the mucosal glycome and pathogens will provide a platform for the rational design of novel strategies to reinforce the mucosal barrier and limit infection by pathogens at critical life stages - infancy, old age and ill-health. Contact: Professor Stephen Carrington 01 716 6238 [email protected] Veterinary, Room 231, Veterinary Sciences Centre, University College Dublin, Belfield, Dublin 4, Ireland OR Dr. Rita Hickey 025 42227 [email protected] Food Biosciences, Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland ********************************************
Posted on: Sat, 25 Oct 2014 14:04:08 +0000
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