RVC Supervisor(s): Dr Alberto Malerba

Department - Comparative Biomedical Sciences

Background, Aims and Objectives:

 Duchenne Muscular Dystrophy (DMD) is a rare X-linked muscular disorder affecting approximately 1 in 5,000 newborn males. Early symptoms include difficulty with movement and an inability to climb stairs. Over time, the disease progresses to a loss of cardiac and respiratory functions, ultimately resulting in death. DMD is caused by mutations in the Dystrophin gene, which prevent the production of the dystrophin protein in muscles. Current treatments show promise, but they offer only marginal benefits to patients. This work aims to optimize a combined Adeno-associated viral vector (AAV) mediated strategy for exon skipping and CRISPR activation of specific genes in order to ameliorate the pathology. This tool will be optimized in relevant cellular models in vitro before being translated into the most used animal model of disease where expression levels of molecular targets, functionality and effect on histopathology will be assessed. The aim is twofold: first, to develop a novel and effective gene therapy approach for DMD; and second, to provide an exceptional training opportunity for a PhD student, equipping them with a wide range of skills in molecular biology, histology, in vitro and in vivo techniques, viral vector production, and more

References

 Cernisova V, Lu Nguyen N, Herath S, Malerba A*, Popplewell L. Microdystrophin gene addition significantly improves muscle functionality and diaphragm muscle histopathology in a fibrotic mouse model of Duchenne muscular dystrophy. International Journal of Molecular Science, 2023, May 3;24(9):8174.  

Malerba A, Sharp PS, Graham IR, Arechavala-Gomeza V, Foster K, Muntoni F, Wells DJ, Dickson G. Chronic systemic therapy with low-dose morpholino oligomers ameliorates the pathology and normalizes locomotor behavior in mdx mice. Molecular Therapy. 2011; 19(2):345-54.  

Gilbert LA, Larson MH, Morsut L, Liu Z, Brar GA, Torres SE, Stern-Ginossar N, Brandman O, Whitehead EH, Doudna JA, Lim WA, Weissman JS, Qi LS. CRISPR-Mediated Modular RNA-Guided Regulation of Transcription in Eukaryotes. Cell. 2013; 154(2): 442-451

Requirements

Essential 

• Highly motivated in pursuing a PhD
• Good interpersonal skills/ability to work as part of a team
• Proactive attitude in design, execution, interpretation and writing up experimental research programmes with support from PI.
• Careful monitoring project-related deliverables and milestone achievements.
• Contribution to the production of research reports, manuscripts and their publication.
• Working to deadlines under time pressure if required.
• Willingness to work with both cellular and animal models of disease.
• The student is expected to work with murine animal models for Duchenne muscular dystrophy.

Desirable 

•  Interest on rare diseases, Duchenne muscular dystrophy or other neuromuscular conditions.
•  Interest on gene therapy applications.
•  Previous knowledge/expertise on:

1. Molecular biology/cloning
2. Quantitative and semiquantitative PCR
3. Western blot
4. Immunohistology
5. Viral vector production
6. Animal work

Fees & Funding

Fully funded at UK home student rate by Muscular Dystrophy UK

Duration 4 year studentship

Location Camden Campus

The studentship will commence 1st March 2026.

Open to applicants eligible for "Home" fees. International applicants are welcome to apply but must be able to fund the difference between "Home" and "Overseas" tuition fees. 

EU/EEA and Swiss national students starting studies in the 2021/22 academic year or later academic years may no longer be eligible to pay the “home” rate of tuition fees nor claim any financial support for their studies dependent on your personal circumstances (including immigration status and residence history in the UK). To help determine whether you would be eligible for home fees please see the UKCISA's 'Who pays 'home' fees for higher education in England?' guide found here.

If you are interested in applying for this position, please follow the link below.  Please use your personal statement to demonstrate any previous skills or experience you have in either cellular analysis or bioinformatics.

How to Apply

For more information on the application process and English Language requirements see How to Apply.

Interviews will take place in person at our Camden Campus OR remotely in December 2025.

We welcome informal enquiries - these should be directed to Dr Alberto Malerba  - amalerba@rvc.ac.uk

Deadline: 30/11/2025