Aldona Ilona Mzyk

Project title: Sensing free radicals in the scarred hearts

Host Institution: Technical University of Denmark (DTU)

Host Supervisor: Dr. Kirstine Berg-Sørensen

Co-host Institution: École Polytechnique Fédérale de Lausanne (EPFL)

Co-host Supervisor: Dr. Giovanni D´Angelo

Summary project: Heart failure is a condition when one’s heart is unable to pump blood around the body properly, which is afflicting more than 23 million individuals worldwide. The myocardial scar formation known as cardiac fibrosis is a key contributor to heart failure. Anti-fibrotic therapies are still under development due to limited understanding of molecular processes behind scar formation. Cardiac fibrosis starts with changes in the mechanical properties of a heart extracellular matrix, which leads to transdifferentiation of cardiac fibroblasts into myofibroblasts. We have very little knowledge about how mechanical stimuli govern fibroblasts plasticity.

My hypothesis is that in a scaring process the ECM mechanical properties influence stiffness of cell organelles, which leads to unbalanced free radicals (FRs) generation. Free radicals, a class of reactive molecules with a free electron, have emerged to be crucial for intracellular signaling.

In the proposed project, I aim to reveal the role of FRs in plasticity of cardiac fibroblasts in response to mechanical stimuli using a new technique called nanodiamond magnetometry combined with optical trapping (fluorescent nanodiamonds will be used as sensors) and complemented by lipidomics.

I will achieve this goal by evaluation of how mechanical stimuli influence FRs generation during intracellular trafficking, by looking for correlations between FRs level and stiffness of organelles as well as lipids profile across the population of fibroblasts. As a consequence, my research will shed light on the mechanobiology of the heart scarring process and provide novel technology that could be used for drug screening.