Project title
Molecular distinction between arrhythmogenic cardiomyopathy and Brugada syndrome
Supervisory team
About the Project
Sudden cardiac death (SCD) is a leading cause of mortality claiming over 6 million lives annually worldwide. And yet we have no truly effective ways to prevent it, mainly because we do not understand it. Arrhythmogenic cardiomyopathy (ACM) and Brugada syndrome (BrS) are two major causes of SCD. Heretofore, they were regarded as separate diseases. Recent evidence, however, indicates significant clinical, pathological and genetic overlap between them. This project will investigate the molecular similarities and differences of these two SCD entities.
We have created sophisticated cellular experimental disease models. We will use whole-cell patch clamping to investigate changes in ion currents and action potential parameters in the presence of mutations underlying ACM or BrS. We will use cutting edge technology to measure conduction velocity and calcium handling in cellular syncytia. Immunofluorescence and confocal microscopy will establish the distribution of key proteins, previously implicated in disease pathogenesis. And we will perform whole transcriptome analysis of cardiac tissue samples obtained from ACM/BrS-driven SCD victims to establish each disease’s RNA molecular signature. These studies will provide much-needed insights into the mechanisms of disease pathogenesis, improve accurate diagnosis and suggest novel, mechanistic therapeutic targets.
Skills acquisition
The project will equip the student with a range of versatile skills including:
- Cell culture
- Whole-cell patch-clamping
- Multi-electrode platform use
- Calcium fluorescence imaging
- Immunocytochemistry
- Confocal microscopy
- TUNEL assays
- Tissue RNA extraction
- Whole transcriptome analysis
Entry requirements
Applicants must have obtained, or be about to obtain, an MSc/MRes or BSc (2i and above) in biology, molecular biology, genetics, biochemistry or a related life sciences field.
Prior experience in basic laboratory skills is essential. Applicants should have an interest in molecular biology, cellular electrophysiology, and bioinformatics.
Funding
The studentship provides funding for three years full-time and includes Home tuition fees plus a tax-free stipend in line with UKRI rates. We welcome applications from international students (EU and rest of the world), but they will normally be required to cover the difference between Home and International tuition fee rates.
Application process
Please send the completed application form to stgeorgesphd@sgul.ac.uk by Wednesday 6 November, 17.00 GMT. An equal opportunities form should also be submitted as a separate document. References will be requested should you be successful in being offered the studentship.
Applications will undergo shortlisting and successful applicants will then be invited to interview week commencing Monday 18 November 2024.
The successful candidate will be given a verbal offer and once it has been accepted, will be sent a formal offer letter and a registration pack with joining information.
Unsuccessful candidates will be contacted with their outcomes at the earliest opportunity and will be able to request feedback if required.