‘Drugging’ Liver Fluke into the 21st Century

Tue10  Apr02:00pm(30 mins)
Where:
Stream 3 - Physics 0.15 Main
Keynote Speaker:
Prof Aaron Maule

Authors

A Maule2; P McVeigh2; E McCammick2; E Robb2; W Hussain1; E Gardiner2; D Wells2; M Tsifaki2; A Margariti2; A Mousley2; N J Marks2
1 Institute for Global Food Security, Queen’s University Belfast, UK;  2 Queen's University Belfast, UK

Discussion

Liver fluke species are pervasive parasites, renowned for undermining the productivity of farmed ruminants and for causing a neglected tropical zoonosis. Despite their sustained economic toll on agricultural production systems, a restricted panel of effective flukicides and mounting evidence for widespread drug resistance, research resources/tools for Fasciola species parasites have languished in the 20th Century, hindering the biological scrutiny needed to underpin drug and vaccine target discovery and validation. Further, after infection peak virulence associates with the migrating juvenile, a stage that has defied biological interrogation based on the challenge of juvenile worm recovery from infected livers at appropriate scale. The last decade has seen a slow, but remarkable progression in the resources and tools available for liver fluke, promoting confidence that these can help advance the development of new control agents. Coincident with liver fluke definitive host promiscuity is the largest helminth genome reported to date that along with improving transcriptomic resources provide new opportunities for in silico discovery. Gene silencing is robust during in vitro maintenance for diverse target genes and a growing panel of bioassays boast refined phenotypic readouts. In vitro maintenance supports long-term laboratory culture, facilitating experimentation on the juvenile, the key life stage for control. Here we will consider how these new tools are supporting advances in our understanding of two elements core to juvenile liver fluke biology: (i) their stem cell-like neoblasts that support the rapid growth and development displayed by migrating worms. These cells drive fluke virulence, offer important new avenues for control and potential tools for the heterologous expression of target genes; (ii) their neurobiology that underpins the sensory and motor coordination needed to support migration from the intestine to the bile ducts. The importance of nerve/muscle targets to nematode parasite control supports the hypothesis that fluke nerve and muscle cells are likely to provide a rich source of flukicide targets.

This work reported here has been supported by BBSRC (BB/H009477/1, BB/K009583/1), NC3Rs (NC/N001486/1), Merial and Boehringer Ingelheim Animal Health.

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