The microturbellarian Macrostomum ligano as a model for the study of parasitic worms

• Main Author: Horan, G. H.
• Published: Queen's University Belfast 2014
• Subjects: 578.6
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.676520

Parasitic platyhelminths are a major burden on humanity through their direct impacts on human health and the huge economic losses they cause, predominantly by undermining agricultural productivity and associated anti-parasite treatments. Previous studies on helminth parasites have highlighted the potential of the neuropeptide signalling system as a source of novel parasite control targets. The use of model organisms is preferable when the target organism is prohibitively difficult or unethical to study directly. The free living microturbellarian Macrostomum lignano is an ideal candidate for the study of parasitic flatworms due to its ease of culture, small size, availability of genomic and transcriptomic datasets and its basal phylogenetic position within the phylum Platyhelminthes. Firstly, this project mapped the distribution of four novel neuropeptides identified from the M. Iignano genome and uses RNA interference (RNAi) on one of those associated neuropeptide genes in an attempt to knockdown the associated transcript and delineate function. Subsequently, the expression of these neuropeptides was examined in selected parasitic flatworms. Despite being successful in the treatment of various parasitic flatworms of animals and humans, the mechanism of action of the anthelmintic praziquantel (PZQ) remains open to debate, hampering efforts to identify mechanisms of resistance and the design of novel drugs which could emulate its effects in parasitic flatworms. The mechanism of action of PZQ was investigated in M. lignano by first determining if the worm was PZQ sensitive. Next the genome was screened for the presence of voltage operated calcium channel (VOCC) β subunit genes (one of the proposed targets of PZQ) which was subsequently silenced using RNA interference to determine if it had a role in PZQ sensitivity in M. lignano. A role for these VOCCs in PZQ action in M. lignano was confirmed using RNAi.