The key player in the ability of cells to move is the so-called actin cytoskeleton. Polymerisation of monomeric actin into polarized actin filaments at the leading edge of migrating cells provides the force for the cells to move. In the evolutionary arms race between host and pathogen, different bacteria and viruses have developed ways to hijack the cell’s own moving machinery to their own advantage, e.g. for infection, replication and spread.
The aim of our group is to obtain a detailed understanding of the structures in the dynamic environment of the actin cytoskeleton and its associated regulators in migrating cells, and in cases where pathogens (focusing on Vaccinia virus and Baculovirus) exploit actin-related host mechanisms. We are trying to understand how cells integrate external signals to form a complex network that allows them guided movement. This includes how both the cell and pathogens use important actin regulators and their upstream activators.
In order to structurally elucidate the molecular details underlying these processes we employ and will actively develop state-of-the-art correlative light and electron microscopy (CLEM), cryo-electron tomography (cryo-ET) methods and image processing techniques. We then combine these methods in an interdisciplinary approach with biophysics, biochemistry and mathematical modeling.
The novelty of our approach is that it will allow us to visualize protein structures directly within their native environments, thus providing an understanding of the structure within its functional context.