This project deals with the role of a structure in cells, the centrosome, that has been known to regulate the cytoskeleton of cells and via this affects processes such as cell division and migration. Our work shows that the centrosome is composed by many different proteins in different cells with unexpected functions - for example we found many RNA-binding proteins and even proteins that process RNA (e.g. "splicing") which normally takes place in the nucleus. Importantly, these proteins are relevant in development and disease, as mutations of the proteins we found at the centrosome are linked to certain diseases. For example, some of these RNA binding proteins are present in all cells of our body, but when mutated in patients the disease only affects the brain. This is an important general question, why ubiquitous proteins when mutated or lost only affect specific tissues or organs. Beyond this very specific focus, we also develop and use techniques in this proposal that are helpful to generally understand how the brain assembles correctly, how its cell type diversity is achieved and how they reach their proper position to allow the complex functions of the brain.
The overall objectives of this grant are to understand the cell-type-specific functions that some of the proteins that are at the centrosome in a cell-type-specific function exert. A focus of this are the RNA-binding proteins, but also cytoskeletal proteins that may regulate unexpected functions. A second main aim is to understand the role of the centrosome in different modes of migration and if its distinct composition contributes to distinct migration modes. Finally, we are aiming to help cells that failed to migrate in a disease context by correcting their migration, e.g. by manipulating specific (centrosome) proteins.
