Role of Dock8-dependent pericentriolar actin structure

The current project aims to understand how immune cells rearrange their shape and internal structure (cytoskeleton) in order to adapt to the environment and navigate our body as part of an immune system response. The main function of the immune system is to defend the body from harmful microorganisms that could damage the organism and cause diseases. For that, immune cells must constantly move through the organism, patrolling the intricate and diverse body tissues in the search of pathogens. This requires a highly dynamic and adaptable cell body and actin cytoskeleton. Coordinated rearrangement of these structures is key to the success of their protective role. It has been recently discovered, that the protein Dock8 is a regulator of actin cytoskeleton assembly. Very little is known so far about the function and relevance of this protein and although Dock8-deficiency has been shown to cause severe immunodeficiencies, the molecular and mechanistic basis of these diseases has not been clarified. We hypothesize that Dock8 is a master regulator of the dynamics of the actin cytoskeleton in immune cells, controlling cell shape and the ability to migrate through geometrically and chemically complex environments. To address this idea, we will use combined biochemical and cell biological approaches as well as advanced microscopy techniques to understand the underlying mechanisms and effector function of Dock8 in the actin cytoskeleton.