De-coding the non-coding transcriptome of Fasciola hepatica

Fasciola spp. liver fluke are globally important helminth parasites of farmed ruminants, and zoonotic pathogens of humans. Prospects for their sustainable control are hindered by the lack of an effective vaccine, resistance to most flukicides, and sub-optimal diagnostic tools that hamper targeted flukicide administration. We aim to address these issues through improved understanding of liver fluke biology, where we have developed methods for long-term in vitro maintenance of juvenile fluke, and RNAi-based interrogation of gene functions, which allow us to silence specific transcripts and study in detail the impacts of those manipulations on worm phenotype. We have generated deep sequencing datasets for micro (mi)RNAs and long non-coding (lnc)RNAs (representing the first description of lncRNAs, and the most comprehensive description of miRNAs yet published, for F. hepatica). We show widespread developmental regulation of both miRNAs and lncRNAs across intra-mammalian parasite stages, suggesting developmentally specific functions for both. The McVeigh lab’s focus is on using these tools and resources to understand the functions of non-coding (nc)RNAs, and in particular, the subset of those that are secreted by parasites into the host environment. To this end, we have identified subsets of miRNAs and lncRNAs in worm secretions, suggesting roles in host-parasite communication, and we have identified potential binding partners for these in ovine and bovine mRNA transcriptomes. When coupled with functional interrogation using the Fasciola molecular toolbox, these data add perspective to the host-helminth interactome and provide new sources for candidate diagnostic biomarkers and innovative therapeutic targets.