Per September 1st 2024, we have a vacancy for two PhD students to work in the group of Dr. Diederik Kuster within the Department of Physiology at Amsterdam UMC. The PhD students will be involved in international projects studying hypertrophic cardiomyopathy (HCM) disease mechanism and building new tools to understand drug response on the cellular level.

HCM affects ~1:200 - 1:500 people. It is the most common inherited cardiac disease. Clinically defined by a unexplained growth of the heart muscle, HCM patients also show impaired relaxation and an increased arrhythmia risk. In more than half of the patients an causative mutation can be identified. These mutations are in the contractile proteins of the sarcomere. Even though these mutations have been known for >30 years, how they lead to a bigger and poorly relaxing heart is not well understood. Over the years the groups of Dr Kuster and Prof van der Velden have contributed to mechanistic and translational knowledge of HCM. These new and exciting projects aim to 1) shed led on the disease mechanisms and 2) understand and expand our knowledge on drug response to increase relaxation.

1) We aim to study the role of the Z-disc in HCM, as this is what couples sarcomeres (contractile units) to each other and is an important mechanosensor in the cell. Based on existing data, major changes are seen in Z-disc morphology and protein expression. We will measure Z-disc changes in human patient samples, study the mechanism for Z-disc remodeling in human induced pluripotent stem cell derived cardiomyocytes and engineered heart tissue. This project is a collaboration between Amsterdam UMC, the University of Birmingham and Charité in Berlin.

2) Our group has extensive expertise in developing tools to measure contraction/relaxation of cardiomyocytes. We are there first that performed drug screenings in cardiomyocytes. We have found a high level of variability in drug response. The mechanism behind this variability is completely unknown. We will develop a new setup that can perfuse and measure individual cardiomyocytes. This allows us to perform for the first time drug responses on an individual cell level. By integrating molecular analysis we will be able to understand the biology of the variable response and test compounds that improve drug effectiveness. This is a collaborative project with small companies from Amsterdam and Sweden.

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 and international partners
• 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.

We are looking for an enthusiastic and ambitious researcher with a strong motivation for doing science. You have a strong interest in physiology, cell and molecular biology and development of new methodologies.

• MSc degree in Medical Natural Science, Biomedical Science, Medicine, Biomedical Engineering Biochemistry or a related discipline;
• High level of independence and the ability to take ‘ownership’ of the project, but are also a pleasant team player able to work with people from different backgrounds;
• Experience with basic science
• A good command, both spoken and written, of the English language.

• We offer an initial contract for 12 months that can be extended (after evaluation) for another 36 months.
• Salary scale: OIO (3.017 tot 3.824 euro based on a 36 hour week), depending on qualifications and experience. The monthly wage will increase yearly to the maximum wage in the fourth year of EUR 3.824 gross per month.
• Additional benefits including an 8.3% end-of-year bonus and 8% holiday pay. Calculate your net salary here.
• Your pension is accrued at BeFrank. A modern and fair pension scheme
• Excellent accessibility with public transportation and reimbursement of a large portion of your travel expenses. Additionally, we have plenty of parking spaces and a good bicycle scheme.

For more information about our employment conditions, please visit our website.

Amsterdam UMC

The Department of Physiology at Amsterdam UMC (location VUmc) performs research in the area of muscle structure and function. The research groups use state-of-the-art physiological and imaging setups, animal models, stem cell-derived models, and human muscle biopsies to study muscle cell structure/function and to achieve insights into the pathophysiology of muscle diseases. For more information please visit the website.

In addition, our research group is embedded in Amsterdam Cardiovascular Sciences research institute. In this research area more than 150 persons from different disciplines (e.g. cardiovascular biology, physiology, health science, exercise physiology, etc.) collaborate.

Working at Amsterdam UMC means working in an inspiring and professional environment in which developing one`s talents and skills is encouraged. We offer you ample opportunity for career development, additional training and a place to grow!