Tissues have unique genome-organisation patterns that fine-tune gene expression, e.g. nuclear envelope (NE)-association enhances gene silencing. These patterns are important as their disruption yields many disorders; however, only ~60-70% of cells achieve their optimal pattern. Schirmer found disruption of muscle genome-organisation patterns alters metabolic gene expression causing Emery-Dreifuss muscular dystrophy (EDMD) while Galloway and Hall identified muscle metabolic changes in athletes, the elderly, and with exercise.
Hypothesis: While disrupted metabolic genome organisation causes EDMD, its further optimisation may enhance athletic performance. We propose that drugs targeting metabolic pathways disrupted in EDMD may improve muscle function in both muscular dystrophy and ageing while generally supporting repair of damaged muscles. Moreover, metabolic changes during exercise might contribute epigenetic regulation to this nexus to further optimise muscle performance.
Aim 1. Relate exercise metabolic changes to genome organisation
The student will compare Galloway/Hall-generated lists of metabolites/metabolic pathways altered during exercise to Schirmer-generated lists of metabolic genes under NE-genome regulation. Where correlations are observed, gene positioning will be determined in muscle from EDMD patients, healthy controls, and athletes before and after exercise using fluorescence-in-situ-hybridisation (FISH). As many NE-regulated genes undergo release or recruitment during development/muscle repair, we predict such genes will undergo rapid repositioning. The student will also learn 4C to test enhancer interactions.
Aim 2. Test metabolic drugs for improving muscle function
Pilot data shows metabolic drug treatment of a tissue culture EDMD model yields improvement in myotube fusion, alignment, and nuclear distribution. Control myotubes also improve with this treatment. The student will test more drug combinations/concentrations using tissue culture myogenesis assays, delivering quantitative data on myotube fusion/alignment, nuclear distribution/genome organisation (FISH), and metabolism (Seahorse metabolic analyser). The student will also learn how to handle human samples, testing these in patient/athlete biopsies.
Aim 3. Do muscle metabolites alter the epigenetic landscape of metabolic genes?
Some muscle metabolites can be used in pathways adding epigenetic marks to genes. The student will learn chromatin immunoprecipitation (ChIP) to determine if changes occur in epigenetic marks on these genes in biopsy material and/or in vitro myogenesis assays using patient/athlete cells. Cells treated with metabolites upregulated in exercise will determine if they can change the epigenetic profile of metabolic genes. Effects of cytokines will also be tested in relation to how fibrosis intersects with these metabolic pathways.
For more information on the project, eligibility and how to apply for the School's PhD programme, please click on the 'Visit Institution Website' link.
Please download and complete the mandatory documents from the EastBio “how to apply” website linked below, before proceeding with your EUCLID application.
Applicants should apply to the School's Biological Sciences PhD programme via the University’s admissions portal (EUCLID) with a start date of 01 October 2026.
In the Euclid application, applicants should state the project “EASTBIO: Spatial Genome Organisation Fine-Tuning of Metabolic Control in Muscle Function in Exercise and Health”, the research supervisor (Professor Eric C Schirmer), their anticipated funding source (e.g. EastBio) and upload their EastBio application form via the Research Proposal Section.
The closing date for applications to be submitted to EUCLID is midday on Monday 15 December 2025.
