Human gastrointestinal bacterial-virus interactions and their role in the pathophysiology of autoimmune liver disease (HLS/DRFAPP7P/61985)

Autoimmune liver diseases (ALD; autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis) impact greatly on health and reduce the quality of life of affected individuals. Emerging data show that the viral component of the microbiome, termed the virome, can have a profound effect on patient physiology (in addition to the effect of the bacteriome). For example, we recently showed that in chronic respiratory diseases the complexity of the bacterial virome’s accessory gene carriage increased in Pseudomonas aeruginosa with the severity and duration of disease (Tariq & Everest et al., 2015). Next-generation sequencing technology and improved resolution of metabolomics technology that can profile metabolites in biological samples, have led to the discovery of a diverse human enteric virome, comprising eukaryotic and bacterial viruses that can link to individual bacteria or stratify according to the progression of the disease. However, in ALD we don’t know what the role of the microbiome is, and more importantly what the impact of the virome is, on the pathophysiology of these diseases.

This PhD project seeks to test the hypothesis that changes in the enteric virome drives the immunological switch from tolerance to a detrimental self-directed immune response within the liver microenvironment in patients with autoimmune liver diseases compared to appropriately matched controls. This collaborative research project using cutting edge genomic (next generation sequencing and bioinformatics) and metabolomic technology on samples from ALD patients and matched healthy controls will (i) identify and compare the gut bacterial microbiome and virome (ii) identify the gut, saliva and serum metabolite profile (iii) identify the metabolic phenotype of immune cells.

Cross-disciplinary training will be provided in molecular biology, microbiology, infection, and immunity. The student will gain significant in-house expertise and training in state-of-the-art-‘omic’ techniques including next-generation sequencing, metabolomics and bioformatics.

It is hoped that the results and findings of this study will guide identification and development of novel therapies for the prospective treatment of these unresolvable chronic autoimmune liver diseases.

Enquiries regarding this studentship should be made to: Dr Simon H. Bridge, 01912274808; [Email Address Removed]

For further details of how to apply, entry requirements and the application form, see
https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/
Please ensure you quote the advert reference above on your application form.