The PhD project I’m working on at the Nanoscopy & NIC@IIT group of the Istituto Italiano di Tecnologia (IIT) concerns the exploitation of advanced optical microscopy techniques to investigate mammalian chromatin architecture. I am specifically interested in the modification in the chromatin organization correlated with oncological processes and genetic diseases. My project aims to develop a biophysical tool to quantify DNA architecture modifications (e.g. 3D compaction) to compare healthy and diseased cells. Furthermore, the effect of mechanical stimuli on the cell nucleus will be studied. To address these questions, I exploit super-resolution microscopy techniques and expansion microscopy in the cell nucleus, trying to adapt them to such a thick and crowded system. Finally, I would like to investigate how modifications in DNA architecture affect the overall functionality of the cell.