细胞生物学博士生职位 - 探索LPCAT3和铁死亡在肌肉疾病中的作用

Award summary

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

Additional funding given to cover research costs

Overview

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 peroxidation, 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 peroxidation, 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 peroxidation 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

Supervisors

Dr Philipp Heher Dr Ana Töpf Professor Volker Straub

Eligibility criteria

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.

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  ‘TC132’  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.

Contact details:

Dr Ana Töpf ana.topf@ncl.ac.uk