Deciphering molecular pathology in facioscapulohumeral muscular dystrophy

Award details

Skeletal muscle plays vital roles in movement, posture, and metabolism, but is impaired in many diseases. Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common genetic neuromuscular disorders, marked by progressive muscle weakness and wasting, leading to declining muscle function and quality of life.

FSHD is driven by abnormal expression of the DUX4 transcription factor, which alters the molecular environment of muscle cells. Our recent research has uncovered how DUX4 causes epigenetic changes (chemical modifications that control how genes are switched on or off), disrupting the genes that are expressed in muscle and so contributing to disease.

This PhD will build on a large, novel dataset generated by our group to:

• Identify specific DUX4-driven epigenetic changes and their impact on gene activity.
• Assess the relevance of these changes in FSHD patient muscle cells and biopsies.
• Pinpoint and test therapeutic pathways that might reverse or prevent FSHD-like defects such as impaired differentiation, mitochondrial dysfunction, and metabolic stress.

These studies will not only advance understanding of FSHD but also provide broader insights into how healthy muscle is normally regulated.

Research Goals

• Map how DUX4 alters the epigenome and transcriptome of muscle.
• Compare these effects with FSHD patient-derived samples to identify robust disease signatures.
• Functionally test candidate pathways to see whether they cause FSHD-like features or can improve muscle cell function when manipulated.
• Identify druggable mechanisms with potential for translation into therapies.

Training and Environment

You will join a multidisciplinary supervisory team spanning King’s College London and the Alan Turing Institute, with a third supervisor of Dr. Massimo Ganassi (m.ganassi@ucl.ac.uk) at University College London (UCL), together offering expertise in molecular biology, muscle biology, disease modelling, and bioinformatics.

The project provides:

• Hands-on training in cell and molecular biology, transcriptomics, epigenomics, and bioinformatics.
• Opportunities to work with patient-derived samples and internationally recognised collaborators.
• Access to the King’s Doctoral Training Programme and transferable skills workshops.
• A strong culture of career development, with previous PhD graduates moving on to competitive academic and industry roles.

 

References

Belayew, A. Rosa, A.L. and Zammit, P.S. (2025). DUX4 at 25: how it emerged from junk DNA to become the cause of facioscapulohumeral muscular dystrophy. Skeletal Muscle 15: 24 (https://doi.org/10.1186/s13395-025-00388-0).

Banerji, C.R.S. and Zammit, P.S. (2021). Pathomechanisms and biomarkers in facioscapulohumeral muscular dystrophy: roles of DUX4 and PAX7. EMBO Molecular Medicine 13: e13695. (doi: 10.15252/emmm.202013695).

Award value

This is a 3-year PhD studentship funded by the charity Muscular Dystrophy UK with the potential for a 4^th year of funding subject to progress.

The preferred start date is 1 February 2026 but applications will be considered for a 1 June 2026 or 1 October 2026 start.

Eligibility criteria

• A first-class or minimum upper (above 60%) second-class degree (or equivalent) in biological sciences, genetics, molecular biology, bioinformatics, or a related field.

• An MSc in a relevant field is desirable but not essential

• Strong interest in muscle biology, epigenetics, or neuromuscular disease.

• Some prior laboratory or computational experience is highly desirable.

• English Language Requirements: Band D

Application process

Please apply for the Basic and Medical Bioscience Research MPhil/PhD (Full-time) using the KCL online application form.

Before completing the application please visit here for information about the programme, requirements and details of what documentation and information needs to be included in your application.

Please include in your application:

• Details of previous employment where applicable

• A 500-word personal statement outlining your motivation for undertaking postgraduate research should be uploaded to the Supporting statement section.

• References: two supporting references are required with at least one academic. Professional references will be accepted if you have completed your qualifications over five years ago.  The prospective supervisors must not be given as referees. Applicant must ensure that their chosen referees are made aware of the requirement to submit the reference before the application deadline.

In the application form under ‘Funding information’: Please select option 5 ‘I am applying for a funding award or scholarship administered by King’s College London’ and under ‘Award Scheme Code or Name’ add 2025/BMBS/07. Failing to include this code might result in you not being considered for this studentship.

 

It is highly recommended to informally approach Professor Peter Zammit before making an application. For administrative and application process enquiries please contact BMBS PGR. 

Selection process

The selection process will involve shortlisting of applicants based on their application. Those shortlisted will be invited for formal interview.