Ph.D. student for the research project “Molecular Mechanisms of Cancer Resistance: The Role of...

The project will address the role of lipid metabolism and its impact on cancer resistance. It is clear that lipid metabolism is altered during carcinogenesis, but is becoming evident that these changes could be linked to the resistance to treatment.

The main aim of this project is to delineate the role of alterations in lipid metabolism coupled with the development or maintenance of cancer resistance. The role of selected crucial enzymes that participate in lipid metabolism will be tested by gain of function (overexpression) and loss of function (knockout, CRISPR/Cas system) studies. We will then assess the impact of such modifications on resistance of these cell lines to cell death induction. Particular attention will be focused on cardiolipin and its metabolism. Cardiolipin is a specific mitochondrial lipid that enables proper assembly of respiratory supercomplexes, thus leading to efficient functioning of the OXPHOS inside mitochondria. Recently, it has been proposed that the mitochondrial function is not only regulated by the quantity of this lipid, but also its quality and the composition of its acyl chains and oxidation status, which greatly affects its biological role. Moreover, the role of lipid oxidation and iron connected with the specific cell death mode called “ferroptosis“ will be also studied.

The experimental model that will primarily be explored is a model of tamoxifen resistant breast cancer cells, due to its high clinical relevance and our previous characterization of its particular metabolic phenotype (DOI:10.1016/j.freeradbiomed.2019.09.004).