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Biological auto-detection and termination of heart rhythm disturbances

Objective

Imagine a heart that could no longer suffer from life-threatening rhythm disturbances, and not because of pills or traumatizing electroshocks from an Implantable Cardioverter Defibrillator (ICD) device. Instead, this heart has become able to rapidly detect & terminate these malignant arrhythmias fully on its own, after gene transfer. In order to explore this novel concept of biological auto-detection & termination of arrhythmias, I will investigate how forced expression of particular engineered proteins could i) allow cardiac tissue to become a detector of arrhythmias through rapid sensing of acute physiological changes upon their initiation. And how after detection, ii) this cardiac tissue (now as effector), could terminate the arrhythmia by generating a painless electroshock through these proteins.
To this purpose, I will first explore the requirements for such detection & termination by studying arrhythmia initiation and termination in rat models of atrial & ventricular arrhythmias using optical probes and light-gated ion channels. These insights will guide computer-based screening of proteins to identify those properties allowing effective arrhythmia detection & termination. These data will be used for rational engineering of the proteins with the desired properties, followed by their forced expression in cardiac cells and slices to assess anti-arrhythmic potential & safety. Promising proteins will be expressed in whole hearts to study their anti-arrhythmic effects and mechanisms, after which the most effective ones will be studied in awake rats.
This unexplored concept of self-resetting an acutely disturbed physiological state by establishing a biological detector-effector system may yield unique insight into arrhythmia management. Hence, this could provide distinctively innovative therapeutic rationales in which a diseased organ begets its own remedy, e.g. a Biologically-Integrated Cardiac Defibrillator (Bio-ICD).

Field of science

  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /medical and health sciences/medical biotechnology/genetic engineering/gene therapy

Call for proposal

ERC-2016-STG
See other projects for this call

Funding Scheme

ERC-STG - Starting Grant

Host institution

ACADEMISCH ZIEKENHUIS LEIDEN
Address
Albinusdreef 2
2333 ZA Leiden
Netherlands
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 485 028

Beneficiaries (1)

ACADEMISCH ZIEKENHUIS LEIDEN
Netherlands
EU contribution
€ 1 485 028
Address
Albinusdreef 2
2333 ZA Leiden
Activity type
Higher or Secondary Education Establishments