- Course: PhD Project funded by the British Heart Foundation
- PhD title: Investigating the mechanisms of action of the clinical drug flecainide on calcium in cardiac muscle cells
Please tell us the title of your PhD?
I am investigating the mechanisms of action of the clinical drug flecainide on calcium in cardiac muscle cells.
What research are you undertaking?
I am undertaking a 3 year British Heart Foundation funded PhD studentship with Prof. Derek Steele within the School of Biomedical Sciences and the Faculty of Biological Sciences.
What is the purpose of your research?
Flecainide is a clinically powerful drug used in patients with atrial fibrillation and in children with the cardiac genetic disorder Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). Patients with CPVT have a mutated protein in their cardiac cells which causes abnormal calcium handling, abnormal heart contractions and often fatal arrhythmias. Flecainide is very effective at preventing these arrhythmias; however the mechanism of action of flecainide within cardiac cells is currently not fully understood.
Initial studies have shown that flecainide may interact with the mutated protein via a novel mechanism of action. If we are able to fully understand how flecainide affects this protein and how it prevents these arrhythmias we can help guide future drug development.
How will this apply to real world applications?
Flecainide radically increases the life expectancy of CPVT patients. However, with increased age comes the increased risk of heart attacks and associated structural cardiac abnormalities. Flecainide can become dangerous when given to adults with structural heart problems. By understanding the mechanisms of action of flecainide, similar and safer drugs could be developed for ageing CPVT individuals.
What facilities and specialise equipment do you use to help you carry out your research?
I primarily image calcium within live, isolated cardiac cells using calcium binding dyes and a confocal microscope. The microscope allows me to image global releases of calcium, as well as take high resolution images of minute releases of calcium from the intracellular stores called “calcium sparks”. Our group also uses the confocal microscope to image fixed cells which are specifically stained with fluorescent antibodies during immunocytochemistry experiments.
What do you particularly enjoy about your research?
Research is full of challenges which must be overcome and enjoying this makes my research a lot more fun! My work is varied – I share my time between the lab and the office which keeps me motivated.
I have had the opportunity to attend and present my work at national and international conferences. I find it exciting to discuss my ideas and results with researchers from other universities working on similar research.
Why did you choose to undertake a PhD?
During my BSc Hons Human Physiology undergraduate degree I was always interested in the process of scientific research. I undertook several research placements during my summer holidays to gain as much experience as I could and I knew a PhD was the right course for me.
Cardiac research was a particular interest of mine and I knew that the research group at Leeds was strong in this field. Since I have begun my project, the topic of flecainide’s mechanism of action has come to a lot of debate within the literature. It’s amazing to be playing a part in such current and fascinating research which could be of real benefit in the future.
What are your plans after you complete your PhD?
After completing my PhD I am keen to continue within scientific research as a Post-Doc and become more involved in written science communication.
Why did you choose the University of Leeds?
The University is great for scientific research and the atmosphere in FBS reflects this. FBS help to ensure that post graduates are able to find friends with similar interests during Induction Week at the start of each academic year, through the Post Grad Society or via the many of the other societies at the Student’s Union.
Leeds itself is a vibrant city full of interesting activities, not just shopping! There are small festivals throughout the summer for food, music and art lovers. It is also a short train ride away from the Yorkshire Dales, some of the most beautiful countryside to cycle through.
What have been the highlights of your time at the University of Leeds?
I have met some lovely people during my PhD at the post grad coffee mornings!
What are your ambitions for the future?
I hope to stay within science throughout my career, both as a researcher and an educator.