EASTBIO: Investigating the mechanism by which endogenous alcohol production by gut anaerobic bacteria impacts disease progression in Non-Alcoholic Fatty Liver Disease

This fully funded, 4-year PhD project is part of a competition funded by the BBSRC EASTBIO Doctoral Training Partnership

Non-Alcoholic Fatty Liver Disease (NAFLD) is a metabolic disorder aligned to diabetes, obesity and hypercholesterolemia that affects nearly 12% of the UK population. Alteration of the gut microbiota has been associated with NAFLD leading to changes in intestinal permeability and translocation of toxic metabolites to the liver, resulting in hepatic injury and fibrosis. Several strands of evidence have suggested that microbial ethanol production determines the progression of this complex metabolic disease. In a study of patients undergoing bariatric surgery, the levels of portal venous ethanol were found to be significantly elevated in patients with NAFLD as opposed to controls, which were then reversed with broad spectrum antibiotics. Genes of ethanol metabolism and specifically alcohol dehydrogenase were upregulated in the liver tissue of NAFLD patients. NAFLD cannot be distinguished histologically from alcohol related liver disease, with several pathological features being shared between both conditions. Finally, metagenomic sequencing of faecal samples from NAFLD patients have correlated their microbial signatures with post prandial ethanol levels. An extreme form of this abnormal fermentation by the gut microbiota has been documented in the ‘auto brewery syndrome’ wherein patients present with alcohol intoxication despite being completely abstinent. These factors underline the necessity to elucidate the molecular mechanisms of microbial ethanol generation in NAFLD in order to develop personalised therapeutic options.

This project will involve a comprehensive culturomic, metabolomic and immunological assessment of ethanol-producing anaerobic bacteria in NAFLD patients and controls. The aim of this studentship is to test the hypothesis that there is a fundamental alteration of anaerobic ethanol-producing bacteria in patients with NAFLD, with pathological production of ethanol and its metabolites, leading to alteration of the gut intestinal barrier and release of pro-inflammatory cytokines leading to inflammation.

This studentship will benefit from the combined expertise of the supervisory team in host-pathogen interactions (Dr Indrani Mukhopadhya), gut anaerobic microbiology  and microbial metabolism (Dr Petra Louis) and metabolomics (Professor Jules Griffin). The project will be best suited for an individual with a background in microbiology, immunology, or similar biomedical degree. The student will use an exciting mixture of laboratory microbiology, immunology, molecular biology, and bioinformatics. Training will be provided for anaerobic bacterial and mammalian cell culture, imaging, conducting challenge experiments and working with different experimental model systems. The Centre for Genome Enabled Biology and Medicine at University of Aberdeen houses DNA sequencing platforms which will be available to the project including training in cutting-edge computational approaches to analyse next-generation sequencing data.

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ELIGIBILITY:

Applicants should hold a minimum of a 2:1 UK Honours degree (or international equivalent) in a relevant subject. Those with a 2:2 UK Honours degree (or international equivalent) may be considered, provided they have (or are expected to achieve) a Distinction or Commendation at master’s level.

All students must meet the eligibility criteria as outlined in the UKRI guidance on funding for postgraduate training and development. This guidance should be read in conjunction with the UKRI Training Grant Terms and Conditions.

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APPLICATION PROCEUDRE:

• Please visit this page for full application information: How to apply | eastbio (eastscotbiodtp.ac.uk)
• Please send your completed EASTBIO application form, along with academic transcripts to Alison Innes at [Email Address Removed]
• Two references should be provided by the deadline using the EASTBIO reference form. References should be sent to [Email Address Removed]
• Unfortunately, due to workload constraints, we cannot consider incomplete applications.
• CV's submitted directly through a FindAPhD enquiry WILL NOT be considered.
• If you require any additional assistance in submitting your application or have any queries about the application process, please don't hesitate to contact us at [Email Address Removed]