ESR1 – Understanding how bacterial adhesins recruit host ligands

Faculty of Biological Sciences, University of Leeds (UK)
This project will involve identification of binding surfaces, crystallisation and structure solution of trimeric autotransporters adhesins by state of the art techniques, the use of engineered binding partners (scFvs etc.) to stabilise the complex. The structures will also be used as the basis for the development of novel anti-adhesive strategies, based on the structures solved. Crystals will be studied at national and international synchrotrons. This is a structural biology project that focuses on understanding how trimeric autotransporter adhesins (TAAs) recognise and bind host factors, building on our work on YadA, and E. coli immunoglobulin proteins to produce the first structures of a complex between a TAA and its ligand. We will apply state of the art binding studies and binding partners towards this goal, and cryoEM as necessary (e.g. Leo et al. & Goldman, Structure 19, 1021-1030 (2011); Bhattacharjee, et al. & Goldman, J. Biol. Chem. 288, 18685-18695 (2013); Wright et al. & Goldman, Acta Crystallogr F 73, 101-108 (2017)). The project will involve secondments to other network partners to test binding via NMR at the University of Oslo, and to the Centre for Nanotechnology and smart materials (CeNTI) in Portugal to test antiadhesive surfaces.