Akbar Group: Extracellular vesicles as mediators and biomarkers of hypertrophic cardiomyopathy (HCM)
- Naveed Akbar
About the Research
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease, caused by mutations in sarcomeric proteins such as MYH7, MYBPC3 and TNNI3. HCM is characterised by left ventricular hypertrophy, fibrosis, and a heightened risk of arrhythmia and sudden cardiac death. However, the molecular signals linking sarcomeric dysfunction to disease progression remain incompletely understood.
Extracellular vesicles (EVs) are nanosized, lipid-bilayered particles released by all cells. They carry proteins, nucleic acids, and lipids reflective of their cell of origin and have emerged as key mediators of intercellular communication and promising circulating biomarkers of cardiovascular disease. Recent work in our laboratory and collaborators has demonstrated that cardiomyocyte-derived EVs from induced pluripotent stem cell (iPSC) models of HCM display altered secretion and molecular cargo, suggesting impaired EV-mediated signalling may contribute to maladaptive cardiac remodelling.
This MSc project will investigate the role of EVs in HCM by focusing on:
Plasma-derived EVs from HCM patients – characterisation of EV yield, size distribution, and surface markers using Nanoparticle Tracking Analysis (NTA), ExoView, and Western blotting.
Molecular profiling of EV cargo – including small RNAs, proteins and lipids, to identify disease-associated signatures linked to myocardial dysfunction using Omics technologies
Integration with experimental HCM models – findings will be compared with existing data from iPSC-derived cardiomyocyte models of HCM to uncover shared or distinct signatures with Professor Christopher Toepfers Laboratory
This project will provide mechanistic insight into how plasma EVs may signal myocardial dysfunction and evaluate their potential utility as biomarkers of disease severity or therapeutic targets.
The project is well suited for a motivated student with interests in molecular cardiology, extracellular vesicles, and translational research.
This MSc by Research project is suitable for part-time research.
Training Opportunities
The student will gain experience in:
Plasma processing and EV isolation (size exclusion chromatography, ultracentrifugation and density ultracentrifugation).
EV characterisation (NTA, ExoView, electron microscopy, Western blotting).
RNA and protein extraction from EVs and downstream Omics-profiling methods.
Bioinformatics approaches for EV-omics datasets.
Translational research approaches, working with clinical and experimental datasets.
The student will be part of the Akbar and Raman Laboratories and collaborate closely with the Toepfer group, gaining exposure to both basic and clinical cardiovascular research. Opportunities to present at internal seminars and external conferences will be encouraged.
Students are encouraged to attend the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.
Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence, and impact. Students are actively encouraged to take advantage of the training opportunities available to them.
As well as the specific training detailed above, students will have access to a wide range of seminars and training opportunities through the many research institutes and centres based in Oxford.
The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.
Additional Supervisors
1. Betty Raman