Per December 1st 2023, we have a vacancy for a PhD student to work in the group of Dr. Tyler Kirby within the Department of Physiology at Amsterdam UMC. The PhD student will be involved in studying nuclear abnormities in the context of
hypertrophic cardiomyopathy (
HCM).
HCM affects ~1:200 - 1:500 individuals worldwide. HCM can lead to a number of cardiac complications, including atrial fibrillation, blocked blood flow, mitral valve disease, heart failure, and sudden cardiac death. Despite the significant advances in our understanding of the underlying mechanisms driving the pathogenesis of HCM, the heterogeneous clinical manifestations of disease have made it challenging to develop targeted therapies that modify disease progression and prevent adverse outcomes. HCM is typically caused by mutations in proteins that are located within the sarcomere (i.e. the contractile apparatus) of the cardiomyocyte, but it is now clear that ~50% of all patients have no known sarcomere mutation. Unexpectedly, even with a broader genetic screening panel, there is no pathogenic mutation identified to explain the hypertrophy in SMN patients, suggesting a novel disease-causing pathway.
This project aims to reevaluate how we think about pathological cardiomyocyte hypertrophy, and test the role of altered nuclear mechanotransduction and subsequent nuclear remodeling in the development of HCM.
As a PhD student you will work in an internationally-orientated research environment, where your main tasks and responsibilities are:
- Set-up, plan and conduct studies, often in collaboration with other researchers in the Department of Physiology;
- Collaborate with clinical partners to study disease mechanisms in explanted cardiac tissue;
- Conduct studies in a recently developed mouse model of HCM;
- Train MSc and BSc students who work with you on your project;
- Writing and publishing scientific manuscripts and other reports on study results;
- Present and disseminate research results at (international) conferences.
This work will result in a PhD thesis based in international, peer-reviewed publications. Training in research and transferable skills are part of the PhD trajectory.