Primary supervisor: Dr Lucy Crouch, University of Birmingham

Non-academic partner: Dr Daniel Spencer, Ludger

Project description

Clostridium perfringens is a strictly anaerobic pathogen that produces a large number of different toxins. It causes a variety of intestinal diseases which are particularly lethal in very young infants. This project will focus on how different C. perfringens clinical isolates access different host glycans and polysaccharides for use as a nutrient source. Once the molecular mechanisms of nutrient acquisition are understood better, it will then be possible to assess which enzymes are virulence factors and possible ways to inhibit colonisation. The student will use microbiology, transcriptomics, enzymology, precision glycobiology, and crystallography to determine the molecular mechanisms of these processes.

Growth assays against an array of human glycans and polysaccharides from 10 clinical isolates (Prof Lindsay Hall’s group) have shown that these different strains have a variety of preferences. The enzymes responsible for these preferences have not been fully identified yet. However, through bioinformatics we have identified candidates that are highly likely to be involved and this is where the student will start. We will also carry out RNA-seq on several isolate-substrates pairs to highlight all the enzymes involved and the student will work with this data to explore the overall question.

This project is likely to have the expected outcome as we have a large amount of preliminary data to produce a successful thesis and publications. Through master’s students, we have already screened several enzymes with different activities, but they need full characterisation. These enzymes include sialidases, endo-O-glycanases, and enzymes active on N-glycans. The worst-case scenario would be enzymes with similar activities to those already published. However, this is unlikely to be the case across everything that we will screen because some of the enzyme families have very few members characterised.

Candidates are encouraged to contact Dr Lucy Crouch to discuss the project before applying if they wish to.