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Title: Bioinformatic analysis of genome-scale data reveals insights into host-pathogen interactions in farm animals
Author: Watson, Michael Bryan
ISNI:       0000 0004 6057 0021
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2015
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This thesis documents the contribution of my bioinformatics research activities, including novel software development, to a range of research projects aimed at investigating the interactions between bacterial and viral pathogens and their hosts. The focus is largely on farm animal species and their pathogens, although some of the research has a wider scientific impact. RNA interference (RNAi) refers to a variety of related regulatory pathways present in animals, plants and insects. The major pathways are microRNAs (miRNAs), small-interfering RNAs (siRNAs) and PIWI-interacting RNAs (piRNAs). Marek’s disease virus is an important pathogen of poultry, causing T-cell lymphoma. We identified the presence and expression patterns of several MDV-encoded microRNAs, including the identification of 5 novel microRNAs. We also showed that not only do virus-encoded microRNAs dominate the mirNome within chicken cells, but also that specific host-microRNAs are down-regulated. We also identify novel virus-encoded microRNAs in other Herpesviridae and provide the first evidence of miRNA evolution by duplication in viruses. In related work, we present a novel microRNA generated by the canonical miRNA biogenesis pathway in Avian Leukosis Virus, another avian oncogenic virus, and publish data showing the expression pattern of known chicken microRNAs across a range of important avian cells. Two of the other RNAi pathways (siRNA and piRNA) form an important part of the antiviral response in arthropods. We have published work demonstrating an siRNA antiviral response to bluetongue virus and Schmallenberg virus in cells from the Culicoides midge, an important insect vector, as well as work demonstrating the importance of the piRNA pathway in the antiviral response to Semliki forest virus (SFV). Further work on flaviviruses in ticks demonstrates the active suppression of the siRNA response by Langat Virus, as well as a key difference between the siRNA responses in Mosquitos compared to ticks. Salmonella is one of the most important zoonoses, with an estimated 1.4 million cases of human salmonellosis per annum in the USA alone. Salmonella infections of farm animals are an important route into the human food chain. This thesis presents work on the comparative structure and function of 13 fimbrial operons within Salmonella enterica serovar Enteritidis as well as a genomic comparison of that serovar with Salmonella enterica serovar Gallinarum, a chicken-specific serovar. We characterised the global expression profile of Salmonella enterica serovar Typhimurium during colonization of the chicken intestine, and we have published the genomes of four strains of Salmonella eneterica serovars of well-defined virulence in food-producing animals. Our work in this area led to us publishing an important and comprehensive review of the automatic annotation of bacterial genomes. Finally, I present work on novel software development. ProGenExpress, a software tool that allows the easy and accurate integration and visualisation of quantitative data with the genome annotation of bacteria; Meta4 is a web application that allows data sharing of bacterial genome annotations from metagenomes; CORNA, a software tool that allows scientists to link together microRNA targets, gene expression and functional annotation; viRome, a software tool for the analysis of siRNA and piRNA responses in virus-infection studies; DetectiV, a software tool for the analysis of pathogen-detection microarray data; and poRe, a software tool that enables users to organise and analyse nanopore sequencing data.
Supervisor: Morrison, Ivan Sponsor: Biotechnology and Biological Sciences Research Council (BBSRC)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: bioinformatics ; farm animals ; genomics ; pathogen