Tool-Driven Advances in Neuropeptide Research from a Nematode Parasite Perspective

Expanding ‘omics’ datasets for parasitic nematodes have accelerated the identification of putative drug targets derived from the nematode nervous system. However, novel drug target validation is hampered by the absence of adequate localisation, functional characterisation, and receptor deorphanisation tools in key nematode pathogens. Reverse genetics techniques have advanced to encompass transgenic, targeted mutagenesis, gene silencing (RNA interference), and genome editing (CRISPR/Cas9) approaches in Caenorhabditis elegans. Unfortunately the translation to nematode pathogens has been slow, such that parasite-focused toolbox development and optimisation is critical. Here we review the discovery, localisation, and functional characterisation toolkit available for parasitic nematode neuropeptide research, and assess the scope and limitations of the tools and techniques for novel nematicide discovery. Enriched nematode parasite ‘omics’ resources have invigorated novel drug target discovery approaches. The value, accessibility, and quality of sequencing technologies and development of in silico mining tools fuel data acquisition. Target identification is no longer an impediment to novel anthelmintic drug target discovery. Existing localisation tools lend themselves well to neuropeptide expression studies in many nematode parasites. Improved techniques, which enhance signal amplification and detection, will boost GPCR localisation prospects. The translation of advanced reverse genetics tools from Caenorhabditis elegans to parasitic species has been slow due to numerous challenges. Toolkit expansion, development, and optimisation strategies in key nematode pathogens will fortify nematode neuropeptide research and augment novel drug development opportunities.