This thesis has used bioinformatics and RNAi methods to investigate diverse aspects of liver fluke biology. In particular, new data on the diversity and expression of liver fluke ABC transporters has revealed previously unrecognised diversity/complexity of this protein superfamily. Some family members were found to be responsive to flukicide pressure suggesting that they may play a role in the normal worm response to drug treatment. Further, RNAi interrogation of their role in resistant fluke isolates supported this link by showing that the silencing of selective ABC transporters increased drug sensitivity - consistent with reduced drug efflux associated with silencing. Further work used RNAi to probe the potential of liver fluke calmodulins as new control targets. These efforts identified target-specific RNAi phenotypes that matched the phenotypes induced by exposure to calmodulin inhibitors, validating the specificity of both the RNAi and the inhibitory drugs. These data support calmodulin candidature as drug targets and further validate the use of RNAi as a tool for functional genomics in fluke. Finally, the work reported here reveals that the serum-induced growth of juvenile fluke speeds up silencing processes and may help researchers refine their approaches to post-RNAi phenotype analyses in the face of the unusually slow/long RNAi-dynamics displayed by liver fluke.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:675457 |
| Date | January 2014 |
| Creators | McCammick, Erin M. |
| Publisher | Queen's University Belfast |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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