Each beat of our hearts is coordinated by electrical impulses generated by the heart tissue itself. These electrical impulses are generated in the muscle cells through the action of ion channels in the cell membrane, allowing entry and exit of charged ions.
Variations in the genes encoding ion channels can cause disruption of the electrical impulses, and can cause a lethal stop of the heart beat. Prediction whether a newly found gene variation is dangerous or not is difficult and requires a lot of experimental work. In this project we will continue development of a new high-throughput method that will speed up and improve such predictions.
We will further develop a combination of automated patch clamping and dynamic clamping. Using these techniques, we can create hybrid biological-digital twins of heart cells that are suitable for studying the effects of the ion channel variants, and will be used to test drug effects. Important advantage of this approach is that we merge the actual biological ion channels into a simulation of the electrical impulses of heart cells, thereby capturing the real biology and real ion channel-drug interactions. Within this project we will develop the implementation of this technique and work towards use in clinical diagnostics.
Key objectives include:
- Optimising expression of ion channel variants in cell lines.
- Performing automated patch clamping experiments.
- Validation of hybrid biological-digital twin methods and experiments.
- Development of protocols for integration of the method in clinical diagnostics.