The project
What if one of the most overlooked organelles in the cell holds the key to survival under stress? Can lipid droplets decide whether a cell lives or dies?
In our lab, we explore how cells reprogram their metabolism to control membrane composition under oxidative stress. Membrane oxidation is the driving force behind ferroptosis, a recently discovered form of regulated cell death implicated in neurodegeneration, stroke, kidney disease, and cancer. A key determinant of ferroptosis sensitivity is the balance between monounsaturated fatty acids (MUFAs), which are resistant to oxidation, and polyunsaturated fatty acids (PUFAs), which are highly prone to oxidation. Yet we still do not understand how cells control membrane acyl-chain composition, or how this balance determines susceptibility to oxidative damage.
Lipid droplets are fat storage organelles that integrate several key metabolic pathways and have been found to contribute to tumorigenesis. But whether and how lipid droplets modulate membrane and organelle homeostasis is unclear. What if lipid storage extends far beyond energy supply and instead serves as a lipid quality control mechanism essential for life?
We propose that lipid droplets actively regulate membrane lipid composition and redox homeostasis in cancer. By controlling PUFA trafficking and storage, they may determine whether cancer cells resist or succumb to ferroptosis. Our goal is to leverage the powerful lipid management system of the LD to enhance membrane PUFA levels and selectively induce cancer cell death.
What You Will Work On
If you are curious about how metabolism shapes cell fate, and how we might exploit it to fight cancer, this project offers an exciting opportunity for cutting-edge research challenges that can make a real impact. Your research will tackle a fundamental and emerging question in cell biology, which will contribute to identifying new therapeutic strategies for cancer. You will work in an interdisciplinary and international environment connecting advanced molecular and cell biology, cutting-edge lipidomics and bioinformatics, redox biology and cancer models.
As a PhD student, you will:
- Genetically and pharmacologically target the lipid droplet-ferroptosis axis
- Dissect how acyltransferases and lipases regulate lipid droplet turnover and membrane remodeling
- Map lipid trafficking pathways using state-of-the-art lipidomics
- Combine molecular and cell biology approaches with single-cell analysis and live-cell confocal microscopy imaging
- Test how metabolic rewiring affects cancer cell growth and resilience to ferroptosis.