PhD Studentship in Cell Biology - Muscular Dystrophy Mechanism Involving LPCAT3 and Ferroptosis

4-year PhD Studentship
100% of home tuition fees and annual stipend of £21,617

Additional funding given to cover research costs

Are you interested in the pathomechanisms of muscle conditions? This PhD project will explore how a novel candidate gene can affect cell membranes resulting in disease.

Preliminary work has identified variants in LPCAT3 in patients with limb-girdle muscular dystrophy. LPCAT3 encodes an enzyme involved in phospholipid remodelling and the maintenance of cell membrane composition. Its function is also closely linked to ferroptosis, an iron-dependent form of regulated cell death driven by an oxidative stress mechanism involving lipid per oxidation, which could induce and/or exacerbate such metabolic stress and propagate muscle weakness and wasting.

The central hypothesis of this PhD is that pathogenic variants in LPCAT3 disrupt phospholipid composition and redox balance in skeletal muscle, increasing susceptibility to ferroptosis and contributing to progressive muscle degeneration.

The student will work across human genomics, clinical research and experimental disease modelling to:

• Identify additional individuals with potentially pathogenic LPCAT3 variants through analysis of >10,000 exomes;
• Establish the clinical, radiological, histopathological spectrum of LPCAT3-related muscle disease;
• Validate candidate variants using targeted RNA and molecular studies;
• Generate patient-derived and/or CRISPR-engineered cellular models;
• Investigate the effects of LPCAT3 dysfunction on phospholipid composition, lipid per oxidation, ferroptosis sensitivity, mitochondrial metabolism and oxidative stress;
• Use transcriptomic and metabolic data to identify potential disease pathways and future therapeutic targets.

The project therefore provides an opportunity both to define a potentially novel form of muscular dystrophy and to investigate an emerging disease mechanism with broader relevance to neuromuscular disease.

The student will receive broad interdisciplinary training in the areas, including NGS variant interpretation, multi-omics analysis, muscle pathology, cell culture and CRISPR-based modelling, lipid per oxidation and redox biology and mitochondrial and metabolic assays.

The project will be based at the John Walton Muscular Dystrophy Research Centre, an internationally recognised and collaborative centre bringing together geneticists, clinicians, pathologists and experimental scientists.

Number of awards: 1

Start date: 04/01/2027

Award duration: 4 years

Sponsor
MDUK

Dr Philipp Heher
Dr Ana Töpf
Professor Volker Straub

A 2:1 honours degree, or equivalent, in Molecular Biology, Biomedical Sciences or 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.

Dr Ana Töpf