Award Summary
This PhD project is focussed on investigating the mechanisms underpinning liver dysfunction in childhood POLG-related mitochondrial disease, also known as Alpers-Huttenlocher syndrome.
The award covers 100% of home (UK) tuition fees and an annual stipend of approximately £21,805 per year (UKRI Rates).
Overview
POLG-related mitochondrial disease is the most common inherited mitochondrial DNA (mtDNA) maintenance disorder and is caused by pathogenic variants in the POLG gene, resulting in mtDNA depletion. Alpers-Huttenlocher syndrome is a childhood form of POLG disease that predominantly affects the central nervous system and liver, with patients developing epilepsy, hepatic dysfunction, or both. Acute liver failure is a particularly severe manifestation that most commonly affects infants and is associated with high mortality. Despite the clinical significance of hepatic involvement, the mechanisms underlying liver vulnerability in POLG disease remain poorly understood, and there are currently no disease-modifying therapies that prevent or treat liver failure.
To investigate the mechanisms underpinning POLG-related liver dysfunction in Alpers-Huttenlocher syndrome, the molecular pathology of donated post-mortem liver tissue from children and adults with POLG disease will be characterised using quantitative untargeted proteomics and immunohistochemical techniques. Using POLG patient-derived induced pluripotent stem cells (iPSCs), hepatic organoids will be generated to investigate disease mechanisms and establish a platform for therapeutic screening.
The awardee will join the internationally recognised Newcastle Mitochondrial Research Group and will be affiliated with the Translational and Clinical Research Institute at Newcastle University and the School of Medicine at the University of St Andrews. The studentship will be based at Newcastle University with the opportunity to do a research placement at the University of St Andrews.
Number Of Awards
1
Start Date
4th January 2027
Award Duration
3 years
Application Closing Date
18/11/2026
Sponsor
This PhD studentship is jointly funded by The Noah Jordan Foundation and Ryan Stanford Appeal.
Supervisors
Professor Robert McFarland and Dr Laura Smith (Newcastle University), and Dr Gareth Sullivan (University of St Andrews).
Eligibility Criteria
A 2:1 honours degree, or international equivalent, in a relevant subject. A Masters with strong research training element would be highly advantageous.
If your first language is not English you need an overall IELTS score of 6.5 (at least 5.5 in all sub-skills) or equivalent language qualification.
International applicants may require an ATAS (Academic Technology Approval Scheme) clearance certificate prior to obtaining their visa and to study on this programme.
How To Apply
You must apply through the University’s Apply to Newcastle Portal
In ‘Course choice’ tab, put ‘Postgraduate Research’ in 'Type of Study', ‘Full Time’ in ‘Mode of Study’, ‘2026’ in ‘Year of Entry’, code ‘8440F’ in ‘Course Title’, blank in ‘Research Area’. Press ‘Search’, select ‘PhD Translational and Clinical Research (FT)’, and save selection.
Either upload a document or write into ‘Personal Statement’. Put code ‘TC135’ in ‘Studentship/Partnership Reference’. When prompted for research proposal, select ‘Write Proposal’. Type in the title of the research project from this advert. A research proposal is not required. You can also upload a covering letter and CV, please state how your interests and experience relate to the project.
You must submit one application per studentship, you cannot apply for multiple studentships on one application.
Interviews will be held 2nd – 3rd December.
Contact Details
Professor Robert McFarland: Robert.mcFarland@newcastle.ac.uk
Dr Laura Smith: laura.alexandra-smith@newcastle.ac.uk
