Unravelling endocannabinoid biology using omics approaches in <i>Strongyloides</i> parasites

This thesis explores parasitic nematode EC signalling function through a multifaceted approach encompassing bioinformatics, functional bioassays, and functional genomics in the model parasite Strongyloides ratti.<br><br>Homology-directed in silico approaches have revealed the conservation of the extended EC signalling network, presenting a series of potential targets linked to nematode EC signalling. Through the design and optimisation of Strongyloides phenotype bioassays significant advances have been made towards a comprehensive Strongyloides bioassay toolkit that will facilitate interrogation of key Strongyloides behaviours.

Exploitation of EC signalling effectors revealed that Strongyloides possess a functional EC signalling system that is putatively linked to key parasite behaviours including nociception, motility, development, thermotolerance, and survival. Further, RNA interference in S. ratti in vitro activated infective larvae (iL3a) has revealed that silencing of an EC ligand biosynthesis enzyme disrupts S. ratti nociception. The data presented in this thesis reveals a fundamental role for EC signalling in parasitic nematode biology and highlights the EC signalling system as a putative source of attractive novel drug targets for parasite control.<br>