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Title: Investigations on RNA interference susceptibility in selected nematodes
Author: Warnock, N. D.
ISNI:       0000 0004 2726 4057
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2012
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Parasitic nematodes continue to be the causative agents of some of the most prevalent diseases of man and cause significant economic losses to the worldwide agri-food industry. With anthelmintic resistance on the rise and environmental concerns over the use of many nematicides the effectiveness of current control options is diminishing. The only viable alternative is the creation of new, environmentally safe drugs/control options. The reverse genetic technique of RNA interference (RNAi) facilitates the examination of gene function by the application of double stranded (ds)RNA complementary to a gene of interest which triggers endogenous cellular mechanisms that destroy the target gene transcript. Of particular interest here is the application of RNAi to nematode species and how this technology could be harnessed to improve our understanding of nematode biology and, ultimately, exploited to inform drug target selection. This study demonstrates that RNAi remains a potentially useful tool for the validation of gene function despite the pressing need to improve experimental rigor and statistical analysis when validating RNAi induced gene knockdown. Although RNAi failed to silence gene expression in the free-living nematode Panagrellus redivivus and was limited in its efficacy in l3 stage worms of the pig parasite Ascaris suum, it did trigger consistent knockdown of selected genes in A. suum adults. A bioinformatic analysis of the RNAi pathway components in the genomes/transcriptomes of selected nematodes indicated the occurrence of all functional groupings within diverse nematodes, suggesting that RNAi mechanisms are in place broadly in the phylum. There were no RNAi effector deficiencies that specifically mapped to RNAi incompetency. As such there remains hope that with further optimisation, and as culture and delivery techniques continue to improve, RNAi could be an important tool for screening gene function and validating drug targets in nematode parasites.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available