Applications are invited for a 4 year fixed term post-doctoral research position based in the laboratories of Prof Per Bullough (sheffield.ac.uk/mbb/staff/perbullough) and Dr. Robert Fagan (sheffield.ac.uk/mbb/staff/robertfagan), and funded by the BBSRC. This project aims to characterise the structure and interactions of the essential Clostridium difficile S-layer with an innovative new type of therapeutic (Acidocin-CD) that targets the S-layer to kill this important nosocomial pathogen. The main structural technique will be cryo-electron microscopy. C. difficile is the most frequent cause of hospital acquired infection across Europe. This highly antibiotic resistant pathogen relies on antibiotic-mediated disruption of the gut microbiota in order to cause disease. There is an urgent clinical need for species-specific antimicrobials that kill C. difficile without further disruption to the gut microbiota. Avidocin-CDs are a promising new type of precision antimicrobial based on naturally occurring phage tail-like particles that efficiently kill C. difficile without collateral damage to the microbiota. The C. difficile cell is coated by a crystalline protein surface layer (S-layer) that mediates contact between the bacterium and its host and environment. This essential surface structure is the bacterial receptor for Avidocin-CDs. With the tools that we have developed over the last few years we are now in a unique position to study the structure of the S-layer, both alone and in complex with a prototypic Avidocin-CD. The successful candidate will join our multi-disciplinary BBSRC-funded collaborative project. The ideal candidate for this post will have a PhD in molecular bioscience (or equivalent experience) and extensive experience of structural biology, ideally including cryo-electron microscopy.
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