Strain-level characterisation and visualisation of microbial communities associated with inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder driven by complex interactions between environmental, microbial and immune-mediated factors. An unfavourable shift in gut microbiome composition, known as dysbiosis, is now considered a key feature of IBD, however it is unclear how specific microorganisms and their interactions with host cells contribute to disease onset and progression. Previous IBD studies have been largely limited to older sequencing methods with low resolution. Furthermore, these studies have predominantly focused on bacterial populations, while other important elements of intestinal ecology (e.g. viruses and plasmids) remain poorly characterised. Together, these limitations have prohibited the comprehensive characterisation of microbial perturbations observed in IBD. The overall aim of this project is to understand how the composition, function and organisation of microbial communities in the epithelial mucosa differ between individuals with IBD and healthy controls.

Approaches/skills and techniques

In this project, high-resolution metagenomics – the sequencing and reconstruction of all microbial DNA from an environmental or clinical sample – will be applied to epithelial mucosa biopsy samples from individuals with and without IBD. Advanced bioinformatic tools will be used to identify microorganisms, including all bacteria, viruses and plasmids associated with IBD, along with functions underpinning disease pathogenesis. Novel fluorescence in situ hybridisation (FISH) approaches will be applied to epithelial mucosa samples, allowing strain-level visualisation of key IBD-associated microorganisms, their spatial arrangement, and interactions with gut epithelial cells.

Outcomes

Together, these approaches will provide the most comprehensive analysis of the intestinal microbiome in IBD to date and will generate fundamental new knowledge on the microbial role in IBD initiation and progression.

Required skills and experience

The ideal candidate will have recently completed a BSc Hons degree or equivalent in a relevant field (microbiology, genomics or biochemistry) with first-class honours (H1), and have a general interest in microscopy and/or microbial ecology. Additional experience with confocal microscopy and image analysis and experience with bioinformatics is preferred.