Investigations of Parasite-Host-Microbiota Interactions Using Cutting-edge Genomics and bioinformatics technologies

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The increased incidence of allergic and autoimmune disorders in developed countries has been attributed to a decline in childhood exposure to pathogens that causes inappropriate immune responses to harmless stimuli. Thus, several attempts have been made to exploit this 'hygiene hypothesis' by reintroducing some of these infectious agents, particularly intestinal worms, into patients as novel immunotherapy. However, the precise mechanisms by which worms modulate the immune system are unclear. Recent studies have established a link between infections by gastrointestinal parasitic helminths and modifications of the composition of the gut microbiota and relative abundance of selected microbial species, thus prompting the hypothesis that the ability of gastrointestinal parasites to modulate the immune response of the vertebrate hosts may be in part associated to changes in the commensal makeup. However, thus far, data on the interactions between parasitic helminths, vertebrate hosts and their commensal microbiota is lacking. Elucidating the complex relationships between the parasite, the host and the gut microbiota is crucial, because of an increasing need for an integrated approach to understand host---pathogen interactions that, in turn, underpin the translation of experimental findings to the clinic. Recent technological advances provide unique opportunities to investigate various aspects of these interactions. For instance, high---throughput sequencing platforms, together with bioinformatics techniques that allow timely processing of large sequence outputs, enable the identification of host genes and microbial populations and/or species associated with the establishment of a parasite in the gastrointestinal tract of its definitive host. The specific research aims of this project will be: (1) to determine helminth---induced changes in gut microbiota following experimental infection of vertebrate hosts; (2) to conduct analyses of transcriptional regulation following parasite infection using next---generation sequencing technologies and bioinformatics; (3) to establish the role of the gut microbiota and the relative contribution of helminth---induced modulation of host gene expression in parasite---mediated suppression of inflammation; (4) to select candidate bacterial species for the development of novel helminth---based therapies of gut inflammatory disorders. This interdisciplinary project will integrate key areas of parasitology, microbiology, immunology, genetics, molecular biology and bioinformatics and will provide essential skills in these areas. This project is timely, since its outcomes will not only have broad implications for future studies of the biology and origin of parasitism itself, but will also pave the way to investigations aimed at exploiting the immunoevasive strategies of parasites for the development of helminth---based therapeutics for chronic inflammatory disorders.