Hannah Van der Maelen

Liquid–liquid phase separation (LLPS) is a novel principle for explaining the precise spatial and temporal regulation in living cells. LLPS compartmentalizes proteins and nucleic acids into micron-scale, liquid-like, membraneless bodies with specific functions, which were recently termed biomolecular condensates. Recent studies have demonstrated that aberrant forms of liquid–liquid phase separation (LLPS) have a crucial role in driving multiple hallmarks of cancer. Dysregulated phase separation can lead to the formation of pathological condensates that disrupt normal cellular functions, contributing to oncogenesis and tumor progression. Understanding the mechanisms driving abnormal LLPS in cancer cells may provide opportunities to elucidate the role of chromatin structure in gene expression regulation. To visualize and characterize these LLPS, we propose to combine fluorescence microscopy with quantitative phase contrast microscopy. Quantitative phase contrast microscopy or quantitative phase imaging are the collective names for a group of microscopy methods that quantify the phase shift (different from the phase separation mentioned above) that occurs when light waves pass through a more optically dense object. Here we would try to obtain the phase shift caused by biomolecular condensates to complement fluorescence data, providing quantitative insights into condensate properties such as size, density, and refractive index. Therefore, this project will employ a multidisciplinary approach integrating cutting-edge imaging techniques, molecular biology, and image analysis to obtain mechanistic insight into LLPS.