Matteo Allegretti

The cell is the simplest living metabolic entity. Organelles are cellular compartments specialised in a certain function. Among them, the nucleus is the largest and most fragile organelle, as it houses and safeguards the genetic material and information. Our group conducts both fundamental and biomedical research projects investigating the macromolecular determinants that define nuclear shape, architecture and remodelling. Notably, nuclear deformations driven by cytoskeletal forces have been shown to impact nuclear transport and gene expression, either through nuclear pore complexes, or via LINC complexes and associated proteins. Furthermore, anomalies in the regulation of nuclear shape and remodelling are directly linked to the biogenesis of diseases such as infertility, developmental disorders, immune defects and cancer metastatic progression. Thus, a molecular understanding of these processes could be key to identifying novel therapeutic targets.

Our group focusses on two experimental model systems: human sperm differentiation and human migratory cells. Using these systems, we aim to reveal the structural organisation and conformational adaptations (molecular plasticity) of protein complexes that shape the nucleus under physiological conditions, environmental stress and pathological states.

We primarily use in-cell structural biology methods, integrating them with light microscopy, single-particle cryo-EM, biochemistry and molecular modelling to investigate the dynamics of protein interactions in space and time. We also develop novel grids, devices and software tools that aim to bridge the fields of structure and cell biology.