Structural biology of viral fibres

Antibiotic resistance in pathogenic bacteria is on the rise and incidences of multi-resistant bacteria increase. At the same time, the discovery of new antibiotics has been slowing down, which means other options to specifically detect and combat pathogenic bacteria have to be explored. Bacteriophages and their derived proteins are one such option. Bacteriophages express enzymes during their infection cycle that target their host bacteria in different ways. Examples are receptor-binding tailspikes that hydrolyse outer cell wall components so the phage can access the membrane in the first step of infection, and endolysins to digest the bacterial peptidoglycan layer in order for the bacteriophage progeny to escape from the cell. Bacteriophage tail fibres may be used to detect bacteria, while their cell-wall degrading proteins may be used to weaken or kill them. 

In our group, we determine the high-resolution structures bacteriophage receptor-binding proteins and endolysins by X-ray crystallography. The atomic structures of the enzymes will allow detailed understanding of their action and mechanism and may suggest site-directed mutations to alter their activity and host specificity. A master student would be involved in preparing expression clones, purifying and crystallising proteins and/or solving their structure by X-ray crystallography.