Authors
L C Cadd2; N J Marks1; A Maule1; A Mousley1; L Atkinson1; 1 Queen's University Belfast, UK; 2 Queens University Belfast, UK Discussion
Parasitic nematodes cause neglected tropical diseases in 1.5 billion of the world’s population and primarily affect the world’s poorest communities. Many of these parasites are soil-transmitted helminths (STHs) including Strongyloides stercoralis, Ascaris lumbricoides, whipworms Trichuris trichiura and hookworms (Ancylostoma duodenale and Necator americanus). Reliance on a limited range of anthelmintics and their sustained overuse is magnifying the risk of parasitic nematode drug resistance and intensifying the need for novel approaches to nematode control. Endocannabinoid (EC) signalling has received significant attention in human medicine due to its role in a variety of key biological processes, including movement, pain, reproduction and appetite. Knowledge of EC-signalling in nematodes is restricted to the free-living model nematode Caenorhabditis elegans, where it is known to modulate cholesterol mobilisation, ageing, axon regeneration, locomotion, feeding and nociception. The EC system in parasitic nematodes is largely uncharacterised, with current knowledge limited to data which suggest that EC-signalling may be involved in host immune modulation during hookworm infections. This project aims to develop a platform for the identification and characterisation of novel drug targets using in silico bioinformatics, in vitro bioassays and functional genomics tools and will exploit this to explore EC signalling biology in Strongyloides spp. The data demonstrate that: (i) key elements of vertebrate signalling networks associated with EC biology are conserved in the genomes of 30 key parasitic nematodes representing 7 clades and free-living, animal-parasitic, entomopathogenic and plant-parasitic lifestyles and, (ii) both novel and established Strongyloides-specific bioassays have the potential to reveal fundamental information on parasite behaviour linked to EC-system function, including aspects of locomotion, sensory ability, development and parasitism. These fundamental data will aid the interrogation of EC-biology post-functional genomics (RNAi), and prioritise putative, novel, EC-targets for validation using CRISPR/Cas9 approaches in Strongyloides species. Knowledge of parasitic nematode EC-signalling systems has the potential to seed novel drug discovery pipelines for parasites of medical and agricultural importance. 
