Wednesday 6th- Thursday 7th November 2024​
Keynote Speaker
Professor Per Bullough
Harrison Chair in Structural Biology
Dept. of Molecular Biology and Biotechnology
University of Sheffield
Research Interests:
Our laboratory focuses on two challenging areas of structural biology - membrane proteins and very large macromolecular complexes. Our main technique is high resolution cryoelectron microscopy, which we often use to complement other structural techniques such as X-ray crystallography.
Offence and defence: structural interrogation of phage attack in C. difficile.
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The molecular details of phage tail contraction and bacterial cell envelope penetration remain poorly understood and are completely unknown for phages infecting bacteria enveloped by proteinaceous S-layers. We are working on the pathogen C. difficile for which we have determined the structure of the S-layer and structures of a number of phages in both their pre- and post-infection states. Surprisingly, in at least one case, we find no evidence of auxiliary enzymatic domains that other phages exploit in cell wall penetration, suggesting that sufficient energy is released upon tail contraction to penetrate the S-layer and the thick cell wall without enzymatic activity. It is also notable that the tail contracts less than those studied in related contractile injection systems such as the model phage T4. Instead, the unusually long tail length, which becomes more flexible upon contraction, likely contributes towards the required free energy release for envelope penetration. I will discuss the structural evidence for different modes of cell envelope attachment and penetration in different C. difficile phages. This work will open the way for the development of novel non-antibiotic therapeutics for C. difficile disease.