PhD candidate Cardiology Department10-03-2022
PhD-candidate in computational modeling of cardiac cellular electrophysiology
The heart’s electrical activity is regulated through complex processes operating on timescales from milliseconds to years. Cardiac arrhythmias result from abnormal electrical activity and are a frequent cause of death and disability. Stabilization of arrhythmias, promoting their maintenance for prolonged periods of time, is a major determinant of such adverse events, but its mechanisms are incompletely understood.
Research during the last 30 years has identified a wide range of molecular mechanisms that can promote cardiac arrhythmogenesis. Ca2+ ions have emerged as critical regulators of cardiac electrical activity (electrophysiology) and contractility. However, calcium-dependent regulation of cardiac electrophysiology transcends those acute (millisecond) timescales via signaling pathways modulating ion-channel function and expression over minutes to days. This calcium-dependent remodeling may be critical for arrhythmia stabilization and can significantly affect the efficacy and safety of antiarrhythmic therapies.
This 4-year PhD project is part of an NWO/ZonMW-funded Vidi project, in which you will join an international and interdisciplinary research team employing detailed mechanistic computer models of the electrical activity of individual heart muscle cells to better understand this long-term regulation of cardiac electrophysiology. You will delve into the fascinating world of so-called excitation-transcription coupling, developing new models with which calcium-dependent signaling pathways controlling the expression of genes regulating cellular electrophysiology can be simulated. This process plays a key role in all our 3 billion heart muscle cells and ensures, among other things, that a large fraction of the electrical components in your heart muscle cell are replaced on a daily basis. The results from this project will be connected to ongoing work simulating ion-channel trafficking. These models can then be employed to integrate available data, design future experiments, predict potential effects of (antiarrhythmic) drugs, thereby providing important new insights into the treatment of cardiac arrhythmias.
Besides working in a welcoming and stimulating translational research environment with a strong track record in publishing translational research with input from experimental scientists, engineers and clinicians, you will have the opportunity to participate in a wide range of courses, as well as seminar series, workshops, etc., to advance your skills. The CARIM School for Cardiovascular Diseases is one of the largest cardiovascular research centers in Europe, embedded within Maastricht University, one of the youngest and most international universities in The Netherlands, which has ranked within the top 10 of the Times Higher Education ranking of Young Universities for the last 10 years. Moreover, the city of Maastricht is a beautiful historic city with strong international character and excellent quality of life.
- You have successfully completed a master’s degree (or equivalent) in technical medicine, (bio)medical engineering, biomedical sciences, bioinformatics or related disciplines;
- You have a strong motivation to commit to an interdisciplinary 4 year PhD-program integrating computational approaches and complex experimental data sets, an interest in cardiovascular research and enjoy working in diverse and international teams;
- The project will involve model development and analysis, primarily in Python and MATLAB. Some previous scripting/programming experience, or a strong motivation to learn these skills is considered a plus.
CONDITIONS OF EMPLOYMENT
Fixed-term contract: 48 months (1+3 years).
Temporary employment of 1.0 FTE for 4 years. The first year will be a probation period, after a positive assessment the position will be extended for another 3 years.
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