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

Project description

Electroporation of biological cell membrane by pulsed electric field treatment

The integrity of the cell membrane presents a barrier that has to be transiently disrupted to deliver therapeutic molecules inside the cell. High-intensity pulsed electric fields (PEFs) are used increasingly in medicine to achieve cell membrane permeability via a phenomenon called cell membrane electroporation. PEF-based clinical applications include gene therapy techniques, DNA vaccination, electrochemotherapy, non-thermal tumour ablation and cardiac ablation. The EU-funded EPmIC project aims to design an approach that will allow an increase or decrease in a cell’s susceptibility to PEF treatment in a controlled, clinically applicable way. The approach is based on the application of modulators of membrane ion channels to influence the extent and longevity of post-pulse membrane depolarisation associated with membrane electroporation.

Objective

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, non-thermal 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.

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Topic(s)

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2019

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Coordinator

UNIVERZA V LJUBLJANI
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 155 288,64
Address
KONGRESNI TRG 12
1000 Ljubljana
Slovenia

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Region
Slovenija Zahodna Slovenija Osrednjeslovenska
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 155 288,64
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