The development of a Porcine Intestinal Organoid to understand Nematode-Host-Microbe interactions using Ascaris suum as a model
Supervisors:
Prof Angela Mousley, School of Biological Sciences and Institute for Global Food Security (Queen's University Belfast)
Dr Louise Atkinson, School of Biological Sciences and Institute for Global Food Security (Queen's University Belfast)
Dr David Smith, Moredun Research Institute
Dr Marc Nicholas Faber, Moredun Research Institute
Dr Tom McNeilly, Moredun Research Institute
Summary:
The control of pro- and eukaryotic microbial pathogens of livestock is challenged by accelerating drug resistance such that the development of novel therapeutics for multi-drug resistant bacteria and helminth parasites is critical. Gastrointestinal nematode parasites (GINs) inhabit the microbe-rich host intestine where they reside alongside a diverse microbiome that may encompass pathogens, including those that cause zoonotic disease. The ability to survive in this hostile environment is supported by nematode innate immunity in part through the production of parasite-derived antimicrobial peptides (AMPs) that can provide protection from harmful bacteria. GINs have also been shown to modulate host microbiomes during active infection however the mechanisms supporting these interactions are unknown.
This project exploits recent progress at QUB (detection of AMPs in nematode biofluids) and MRI (Organoid development) to establish a porcine intestinal organoid-microbial co-culture platform for interrogation of Ascaris suum biology at the host intestinal interface. The student will receive multi-disciplinary training (bioinformatics, molecular biology, microscopy, Omics technologies, cell, nematode and microbe culture) to explore the putative roles of parasitic nematode AMPs in shaping the host microbial community, protecting against invading pathogens, and parasite survival. The project has the potential for novel drug target identification for GINs and may reveal novel bioactives against microbial pathogens.