Post-doc Researcher in Ca2+ dysregulation and arrhythmias in human heart failure

(ref. BAP-2023-51)

Laatst aangepast : 26/01/2023

Summary Box: Dysregulation of Ca2+ handling is a key feature and a mediator of the pathophysiology of cardiomyocytes in heart failure and ageing. We have an open post-doc position to investigate Ca2+ signalling between InsP3R, RyRs and connexin hemichannels in ventricular arrhythmias in human heart failure and ageing. This position builds on recent our recent identification of a contribution of Ca2+ release via RyRs to the activation of connexin hemichannels (De Smet et al., JCI 2021) and of InsP3R-RyR crosstalk (Jin et al., BRIC 2022) in arrhythmia generation. In this project, we will extend our analysis to probe how InsP3R signalling is involved in hemichannel opening and the conditions under which this pathway is engaged. The influence of InsP3R-Cx crosstalk on cellular arrhythmia propensity, contraction and excitation propagation will be explored. The project will involve dual voltage/calcium imaging of living cardiac slices, acutely isolated cardiomyocytes from human and from sheep models of ageing and disease. Genetic manipulation in cultured cells and slices will be employed to directly probe individual contributions of the players involved. This project is part of a recently funded FWO project with the Laboratory of Prof Luc Leybaert at University of Ghent, which focusses on the use of mouse models to examine connexin hemichannels in arrhythmia generation. Smet, M.A.J.D., A. Lissoni, T. Nezlobinsky, N. Wang, E. Dries, M. Pérez-Hernández, X. Lin, M. Amoni, T. Vervliet, K. Witschas, E. Rothenberg, G. Bultynck, R. Schulz, A.V. Panfilov, M. Delmar, K.R. Sipido, and L. Leybaert. 2021. Cx43 hemichannel microdomain signaling at the intercalated disc enhances cardiac excitability. J Clin Invest. 131. doi:10.1172/jci137752. Jin, X., M. Amoni, G. Gilbert, E. Dries, R.D. Puertas, A. Tomar, C.K. Nagaraju, A. Pradhan, D.I. Yule, T. Martens, R. Menten, P.V. Berghe, F. Rega, K. Sipido, and H.L. Roderick. 2022. InsP3R–RyR Ca2+ channel crosstalk facilitates arrhythmias in the failing human ventricle. Basic Res Cardiol. 117:60. doi:10.1007/s00395-022-00967-y. Organisational Unit: The Laboratory of Experimental Cardiology: The Laboratory of Experimental Cardiology sits alongside clinical and basic research groups within the Department of Cardiovascular Sciences involved in translational research investigating cardiac structural, contractile and electrical remodeling processes during cardiovascular disease. Our research spans from the study of genome regulation by omics approaches (including single cell) through cellular analysis to investigations of the physiology and function at the tissue and organ level. The laboratory is highly international consisting of post-doctoral scientists, PhD students and technicians. We also collaborate widely with external partners to advance our research and provide opportunities for training. The laboratory has a wide range of state-of-the art equipment required to examine the molecular and physiological changes involved in cardiac remodelling. Our laboratory has dedicated systems for imaging and electrophysiology including of living cardiac slices, high throughput cell analysis, and for confocal microscopy. The lab is also fully equipped for molecular biology and protein biochemistry. Through interactions with the transplant and surgical teams of KU Leuven, we have regular access to explanted and non failing human heart tissue. Collaborations with the Laboratories of Cardiac Surgery and of Cardiac Haemodynamics and Imaging provide access to large animal models of disease and ageing. Extensive training and support will be available to gain expertise in all areas. Through our excellent local and international collaborators and core facilities, you will have access to additional expertise and tools. The Department: The Department Cardiovascular Sciences is situated in the Biomedical Campus of KU Leuven. It has the entire range of competences from basic science, over pre-clinical modeling to applied clinical and epidemiological research, taking a systems approach to the complexity of cardiovascular disorders. The University: KU Leuven offers a stimulating environment for international students and support for junior scientists to achieve their ambitions and in career development.

Responsibilities

You will develop and drive forward your own project and take opportunities to extend your findings.
You will contribute to guiding students in the laboratory.
You will be expected to develop expertise in areas necessary for successful progress of your project. 
You will be expected to perform experiments ranging from cell biological to in vivo analysis.
You will be expected to present your work at conferences, lab meeting, and departmental meetings.

Profile

You are motivated, have an enquiring mind and are excited by science.
You hold a PhD degree in Physiology, Biomedical Sciences, Cell Biology,Biochemistry or other similar domain of life sciences with working knowledge in relevant areas.
You ideally have experience in calcium imaging and/or electrophysiology. 
You have experience in cardiomyocyte biology/physiology and are driven to establish mechanisms linking physiology and cell function/pathology.
You have a demonstrated ability to perform high-level biomedical research.
You enjoy collaborating with your colleagues and externally to scientific advance.
You are a team player with excellent written and oral communication skills in English
You are an independent thinker who can drive a project forward.
You enjoy presenting your data to collaborators and to the community at scientific meetings.
You perform your research to the highest standards and integrity.

Offer

A position for 3 years with possibility for extension.
A stimulating and supportive environment in which you acquire expertise as a multidisciplinary researcher.
Access to contemporary equipment, expertise and thinking in cardiovascular research.
Opportunity to develop your independence. 
Support and mentorship to apply for independent funding from the national and international funding agencies including the Flemish Research Council (FWO) and the EU.

Interested?

Please send your CV, motivation letter and 2 recommendation letters to Prof. Dr. H. Llewelyn Roderick Email: ([email protected])or Prof K Sipido, Email:[email protected]). Please also apply via the online portal of KU Leuven.

KU Leuven seeks to foster an environment where all talents can flourish, regardless of gender, age, cultural background, nationality or impairments. If you have any questions relating to accessibility or support, please contact us at [email protected].