项目介绍

2024年6月2日

The Lab of Experimental Cardiology is part of the Department of Cardiovascular Sciences at the KU Leuven and includes research teams led by Prof. Eef Dries and Prof. Llewelyn Roderick. The joint focus of our teams is to study cellular and molecular mechanisms that underlie the physiological and structural changes in the heart that occur during disease and ageing that contribute to decreased function and arrhythmia. Our experimental approach combines a variety of advanced physiological and molecular technologies, ranging from single cell analysis to the use of multicellular native and engineered preparations as well as in vivo. The goal is to bridge the gap between basic research and clinical observations with the ultimate aim of defining new targets for therapy.

Project

The team of Prof. Eef Dries is recruiting a PhD student to study underlying mechanisms contributing to arrhythmogenesis in cardiac disease. We previously studied aberrant Ca2+ handling (ectopic calcium release events) in isolated single cardiomyocytes in the onset of arrhythmia after disease remodelling (Dries et al. 2018). The obtained findings were translated to in vivo using a large animal model with myocardial infarction (Dries & Amoni et al. 2020). As a continuation of this work and to gain deeper insights into how changes in cardiomyocyte physiology affect tissue function, we will use a new living tissue slice experimental model in which calcium and voltage changes can be simultaneously monitored. Using this slice model in which cell-cell and cell-matrix interactions are preserved, a more physiological perspective of the impact of cardiomyocyte dysfunction and greater insights into the impact on the intact organ can be obtained.
The research project is centred around the following objectives:

• Understanding how aberrant calcium handling contributes to arrhythmogenesis in diseased cardiac tissue.
• Testing interventions that could modify defective calcium handling in cardiac tissue.

The candidate will prepare living cardiac slices from human samples of different disease etiologies and perform advanced live calcium and voltage imaging, which they will combine with molecular analysis (Dries et al. 2021). Identified mechanisms will then be targeted using pharmacological interventions and/or genetic modifications.
Key methodologies used in this project include: living cardiac tissue slices (Watson et al. 2017), live fluorescent imaging (calcium and voltage indicators), cardiac tissue culture, confocal microscopy, immunostaining, immunoblotting, viral vectors and transduction.
The team has a long-standing expertise in cardiac electrophysiology, Ca2+ homeostasis and remodelling with disease. Extensive facilities are available for functional imaging, electrophysiology, access to large animal models and human cardiac tissue samples. The research group has several postdocs and doctoral students.
Funding is available to support the position and the research.
The candidate will enroll in the Doctoral School offering further training and complementary skills’ development.
Selected References:

• Dries E, et al. Hyperactive ryanodine receptors in human heart failure and ischaemic cardiomyopathy reside outside of couplons. Cardiovasc Res. 2018 114(11):1512-1524. doi:10.1093/cvr/cvy088.
• Dries E, Amoni M, et al. Altered adrenergic response in myocytes bordering a chronic myocardial infarction underlies in vivo triggered activity and repolarization instability. J Physiol. 2020 Jul;598(14):2875-2895. doi: 10.1113/JP278839.
• Dries E, et al. CaMKII inhibition reduces arrhythmogenic Ca2+ events in subendocardial cryoinjured rat living myocardial slices. J Gen Physiol. 2021 Jun 7;153(6):e202012737. doi: 10.1085/jgp.202012737.
• Watson S, et al. Preparation of viable adult ventricular myocardial slices from large and small mammals. Nat Protoc. 2017. 2(12):2623-2639. doi: 10.1038/nprot.2017.139.

Profiel

• We are looking for an enthusiastic and highly motivated candidate with a Master degree in Biomedical or Life Sciences (or equivalent). In depth knowledge of relevant areas, in particular cardiovascular system and cell physiology is expected.
• You are flexible, able to work independently as well as in a team and have a problem-solving attitude.
• You are interested to work with samples from patients and large animal models.
• You are motivated to work in a multidisciplinary research team and have good communication skills in English.
• You are expected to write a doctoral thesis within 4 years.
• A creative and technical mindset is a plus.

Aanbod

• We offer a fully funded doctoral fellowship (based on successful intermediate evaluation after 1 year).
• We provide excellent research facilities and opportunities for broader skill development (training, education and career development).
• You will be part of a multinational research group.

Doctoral School
Department of Cardiovascular Sciences

Interesse

For more information please contact Prof. dr. Eef Dries, tel.: +32 16 37 94 54, mail: eef.dries@kuleuven.be or Prof. dr. Llew Roderick, tel.: +32 16 37 71 50, mail: llewelyn.roderick@kuleuven.be.You can apply for this job no later than July 08, 2024 via the online application tool

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