Identification and characterisation of antimicrobial peptides in parasitic helminths

This thesis integrates multiple laboratory-based methods and computational tools including bioinformatics, microbiology and molecular biology to characterise helminth AMP diversity and begin to unravel AMP function in helminths.<br><br>Through homology-directed and machine learning AMP identification and prediction approaches, the data generated here highlight helminths as a major source of AMP diversity. These analyses reveal major differences in the distribution of putative AMP-encoding genes across phylum Nematoda and Platyhelminthes, with specific helminth taxa displaying restricted AMP profiles.

Through exploitation of published RNAseq datasets, putative AMP-encoding genes were also shown to be expressed in key parasitic life stages supporting prioritisation of AMP-encoding genes for functional analyses. Eight novel helminth-derived AMPs, identified via a unique computational AMP discovery pipeline, displayed antibacterial activities against pathogenic microbes demonstrating that helminths may also be a source of antimicrobial diversity for the development of novel therapeutics.

Finally, efforts to unravel the function of AMPs in adult Ascaris suum via RNA interference highlighted that novel approaches are required to uncover the role of helminth AMPs and their importance to nematode biology. The data presented in this thesis represent a significant advance in our understanding of helminth-derived AMPs and provide a springboard for functional analyses that will reveal the potential for helminth-derived AMPs as novel therapeutic targets for pathogen control.