Liver fluke development : a target for parasite control?

Fasciolosis, a debilitating disease caused by flatworm parasites belonging to the genus Fasciola, is a prominent threat to global food security due to its widespread infection of agriculturally significant ruminants. Recent studies have identified a population of proliferative cells within Fasciola hepatica (Fasciola proliferative cellsFPCs) that resemble neoblast-stem cells, both morphologically and behaviourally. These cells are the only proliferating cells in Fasciola hepatica and can be localised using thymidine analogue 5-Ethynyl-2 ́-deoxyuridine (EdU). This thesis further characterises these neoblast-like stem cells, investigating their dynamics, supportive roles in growth and development and identifying putative regulatory effectors. This study reports increased juvenile growth, which correlated with increased proliferation of these stem-like cells, in juveniles maintained in chicken serum supplemented media (CS+). The comparison of FPCs between in vitro maintained and ex vivo maintained juveniles further supports the link between FPCs and juvenile development, with the larger, more developed ex vivo juveniles exhibiting significantly more proliferating cells. FPCs were found to be radiation sensitive enabling us to selectively deplete them and examine downstream effects. Using an RNA interference (RNAi) platform, the function of a key effector (fgfrA) was investigated and silenced juveniles exhibited a significant reduction in the number of EdU+ cells. The findings of this study highlight the stem-like characteristics of FPCs, their facilitative roles within fluke growth and indicate their importance to fundamental fluke biology. The disruption and dysregulation of this cell population may hold the key to developing novel control therapies.