Objective
Cardiac arrhythmias like atrial fibrillation (AF) and scar/fibrosis related ventricular arrhythmias (VA) are responsible for significant morbidity and mortality. Yet, the mechanisms underlying their initiation and perpetuation are, in many cases, unclear and their treatments inadequate. These limitations stem, in part, from the lack of suitable complex human arrhythmia models and the inability to introduce reversible targeted functional interventions in the system. Here we propose to develop advanced 3D human cardiac tissue models that can recapitulate the patient-specific structural and electrophysiological substrate and combine them with novel optogenetic interventions to study cardiac arrhythmias. Specifically, we propose to combine patient-specific engineered human induced pluripotent stem cell (hiPSC) derived cardiac cell subtypes with photolithography micropatterning, decellulrization/recellularization, and 3D bioprinting to establish advanced tissue models (Aim 1). Novel optogenetic tools and concepts will then be developed to facilitate modeling of the underlying arrhythmia substrate, for robust and reproducible arrhythmia induction (“arrhythmia printing”), to decipher the mechanisms and to identify critical sites for arrhythmia maintenance; and to introduce new therapeutic concepts (Aim 2). These tools, together with clinical imaging/pathological samples serving as templates, will be used to generate models of the ventricular infarct border-zone (and other fibrosis patterns) to study VA (Aim 3) and the healthy and diseased atria to study acquired and inherited AF (Aim 4). Lessons learned from these studies will be evaluated in relevant animal models. The described approach represents a paradigm shift in the way cardiac arrhythmias can be studied and treated. If successful, it will provide a tailored approach towards novel mechanistic insights into different rhythm disorders, allow patient-specific risk-stratification and provide novel therapeutic options.
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Keywords
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-ADG
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32000 Haifa
Israel
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