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Title: The role of microRNAs in the host-parasite relationship in the veterinary nematode Haemonchus contortus
Author: Gu, Henry Yuekun
ISNI:       0000 0004 6060 5247
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2016
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Haemonchus contortus is one of the most pathogenic nematodes of small ruminants, particularly sheep, and has a major impact on welfare as well as causing significant economic losses to farmers worldwide. In this project, the possible interaction of parasite microRNAs with the host’s immune response was investigated with a view to determining whether microRNAs may enhance parasite survival. microRNAs are 22 nucleotides long, non-coding RNA molecules that bind to target sites with complementary sequences on mRNAs, usually in the 3' UTR. This interaction causes degradation of the mRNA or suppression of protein synthesis (Bartel, 2009; Selbach et al., 2008). A previous study identified 192 microRNAs in H. contortus, a large proportion of which were unique to parasitic nematodes (Winter et al., 2012). One particular microRNA, Hco-miR-5352 is of particular interest and is the major focus of this study. This microRNA is one of a cluster of four microRNAs (the miR-5352 cluster) which is conserved predominantly in nematodes that reside within the gastro-intestinal tract. Microarray and qRT-PCR data show that the miR-5352 cluster was most highly expressed in parasitic stages of the H. contortus life cycle. Some members of the cluster were detected in the excretory-secretory products of H. contortus as well as in abomasal and lymph node tissues taken from sheep infected with H. contortus. Transmission electron microscopy of the excretory-secretory products showed the presence of small vesicle-like structures. The data presented here showed that H. contortus releases a range of microRNAs in the excretory-secretory products, some of which were present within extracellular vesicles. Bioinformatic target prediction methods identified CD69 as a likely target of Hco-miR-5352 and this interaction was demonstrated experimentally using a dual luciferase assay. However the interaction was not confirmed using an inducible CD69 system in Jurkat T cells. The impact of Hco-miR-5352 on global gene expression of an intestinal epithelial cell line identified several interesting targets with important roles in the host immune response against H. contortus, the regulation of which may be important in parasite survival within the host.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: QH345 Biochemistry