Probing in vivo parasite biology in vitro

Helminth parasites impose a huge burden on human health and agricultural productivity. Amongst the most important parasites of livestock are Fasciola species liver fluke that cause fasciolosis - also a neglected tropical disease. The predicted impact of climate change on fluke epidemiology and growing drug resistance emphasise the need for new flukicides / vaccines. Unfortunately, major impediments to research that advances new control target discovery/validation have included the lack of good bioinformatic resources, the absence of a model system for functional studies and the reliance on host animal-based in vivo experiments to inform fluke biology; the reliance on in vivo efficacy studies in host animals impedes significantly the drug discovery process. 

The new liver fluke genome sequence and the development of functional genomics tools expose a compelling need for in vitro tools for juvenile fluke to facilitate studies of their biology. In this respect we have made significant advances in their in vitro maintenance that facilitate fluke survival for >7 months (with >70% survival). Although our methods facilitate marked growth and development of the gut, tegument and reproductive systems, these are slower than those seen in vivo. This project will build on these new resources and preliminary data to enhance in vitro fluke culture. The work will be underpinned by comparative studies (behavioural, morphological, pharmacological and transcriptomic) of in vitro and in vivo fluke to validate the utility of functional/phenotypic readouts. This project aims to deliver an in vitro toolkit for liver fluke that is robust and translational (i.e. predictive of in vivo outcomes) and enables the study fluke developmental biology, the validation of new drug targets and the screening new drug candidates. Progress made here will contribute significantly to the replacement of animals for studies of parasite biology.