ESR4 – Binding studies of bacterial adhesin heads with extracellular matrix components

Department of Biosciences, University of Oslo (Norway)
This project combines modern structural biology and biophysical techniques (mainly NMR) with classic molecular biology methods (cloning, mutagenesis). The project is focused on understanding the molecular details of a bacterial adhesin and its capacity to bind to extracellular matrix components such as collagen during the infection process. The project builds on previous work of the group on the trimeric autotransporter adhesin YadA (e.g. Mühlenkamp et al., J Innate Immun. 9, 33-51 (2017); Shahid et al., Nat Methods 9, 1212-1217 (2012)) and on related proteins from Salmonella and other species (e.g. Hartmann et al., PNAS 109, 20907-20912 (2012); Schmidgen et al., J. Bacteriol. 196, 2155-65 (2014)). We will apply state of the art binding studies using protein labeling techniques and solution NMR or solid-state NMR spectroscopy as necessary to identify binding surfaces and interfaces. The constructs used in these studies will also be employed as surface coatings in lab-on-a-chip diagnostic assays. To this end, the project will involve secondments in companies working with diagnostic chip development within the network (ELISHA, Eluceda, both located in the UK). Planned secondments also include visits to the Institut Pasteur (Paris, France) for NMR data evaluation.