The macromolecular determinants of nuclear shape
Our lab aims to understand how macromolecules organise and interact in order to react to different stresses transmitted to the nucleus in healthy and pathological conditions. High-resolution details of such organisation can help us to understand the molecular basis of nuclear remodelling, including several disease phenotypes linked to aberrant nuclear architecture (ageing, cancer, developmental disorders). We work on cell migration, which requires a specialised nuclear architecture to prevent DNA damage. The primary objective of the lab is therefore the investigation of the structural organisation and conformational adaptations (molecular plasticity) of protein complexes that rule nuclear architecture and shape in situ upon differentiation (spermatogenesis), or during cell migration. Mutations and alterations in these protein complexes are frequently associated with diseases states and nuclear deformations have been shown to impact nuclear transport and gene expression. To investigate such processes we use two different human model systems: sperm cells and somatic migratory cells. Our focus is on the mechano-chemical principles that alter nucleus-cytoskeleton structure and coupling. We aim to elucidate the higher-order nucleus-cytoskeleton architecture required for those processes across various human cell types, including cancer cells. We employ in-cell structural biology techniques, integrated with complementary structural and cell biology methods.
nucleo-cytoskeleton interaction in fibroblasts