Controlling the susceptibility of biological cells to pulsed electric field treatment by using ion channel modulators

Controlling the susceptibility of biological cells to pulsed electric field treatment by using ion channel modulators (2021-2023)
Head: doc. dr. Lea Rems, Univerza v Ljubljani, Fakulteta za elektrotehniko
Partner: /
Funding: EC – European Commission
Code: 893077 — EPmIC

 

The research project is funded by the European Comission.

Member of University of Ljubljana

University of Ljubljana, Faculty of Electrical Engineering

Code
893077 — EPmIC
Project
Controlling the susceptibility of biological cells to pulsed electric field treatment by using ion channel modulators
Period
01.03.2021 - 20.04.2023
Amount of financing
1 FTE
Head

Assist. Prof. Lea Rems

Research activity
ENG - Information Science and Engineering
Research Organisation

University of Ljubljana, Faculty of Electrical Engineering

Abstract

The integrity of the cell membrane, while essential for life of any biological cell, presents a barrier that sometimes needs to be transiently disrupted in order to deliver therapeutic molecules inside the cell. High-intensity pulsed electric fields (PEFs) are used increasingly in medicine to achieve such increase in cell membrane permeability via a phenomenon called cell membrane electroporation. PEF-based clinical applications include gene therapy techniques, DNA vaccination, electrochemotherapy, nonthermal tumor ablation, and cardiac ablation. Depending on the desired outcome of the PEF treatment, the targeted cells must either survive or die. However, different cell types exhibit different susceptibility to PEF treatment, with some cells being killed at lower pulse amplitude than others, which often presents a disadvantage that limits the safety and efficiency of PEF treatment. In this action I aim to design an approach that will allow us to increase or decrease cell’s susceptibility to PEF treatment in a controlled, clinically applicable way. The approach is based on using modulators of membrane ion channels, that can influence the extent and longevity of post-pulse membrane depolarization – a hallmark of membrane electroporation. My idea is on the one hand inspired by increasing amount of evidence showing the involvement of ion channels in PEF-induced cell response, and on the other hand by the fact that ion channel modulators are already successfully used in treatment of various diseases and we can expect exciting development of new modulators in the near future. The design will be guided by state-of-the-art microscopic techniques and computational models, including molecular dynamics simulations, particle-based simulations, and finite element modeling, that will help elucidate the molecular mechanisms of membrane depolarization and choose the appropriate modulators and pulse parameters for fine-tuning the treatment outcome.