UK-HEI Studentship: The biochemical and structural properties of a newly identified class of proteins 'adhesins' in mediating bacteria-gut interactions

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This is a Norwich Research Park studentship between IFR (Nathalie Juge), JIC (Rob Field) and UEA (Andrew Hemmings). The aim of the work is to obtain structural basis for the interaction between bacteria and the mucus layer by focusing on the study of mucus binding proteins from major bacterial species. Intestinal tract mucins are principal components of the mucus layer on epithelial surfaces, and perform a protective function against microbial damage. However, little is currently known regarding the interactions between commensals/pathogens and epithelial cell mucins. The diverse oligosaccharide sequences present on mucin-type glycoproteins are potential sites of attachment, mediated by bacterial “adhesins”. Deciphering structural motifs critical for recognition of mucus constituents will open up an essentially unexplored area of host-microbe interaction research.
Specific objectives of the project include:
- Recombinant expression, mutagenesis and characterisation of MuBPs (IFR)
- Glycan recognition studies by biophysical techniques (JIC)
- Protein X-ray crystallography and bioinformatics (UEA)
Together with biochemical analyses, the proposed structural studies will aid indentifying the molecular determinants of sugar specificity and consequently biological activities of this new class of “adhesins”. This study complements other studies aimed at understanding the role of protein-carbohydrate interactions using whole cell systems. The approach presented here benefit from the exceptional combination of complementary skills presented by the NRP partners at UEA, IFR, JIC, involved in this study.

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