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Medical and health sciences
- Cellular interactions and extracellular matrix
- Intracellular compartments and transport
- Cell movement
- Cytoskeleton
This project will investigate the function, structure and dynamics of a particular organelle in immune cells, osteoclasts, endothelial cells, neural crest cells and cancer cells. It consists of many different proteins that together build up a so-called invadosome. This is a molecular tiny 'drill' that makes holes in the underlying basement membrane. This allows immune cells to engage pathogens that are hidden somewhere in tissues, but also allows cancer cells to escape from the primary tumor and cause lethal metastases. The invadosome is very small but can be visualized with powerful microscopes. In this project, we will combine a unique approach to image these structures and understand how they operate and built, at the highest resolution, giving the most detailed images. The Gettemans lab in Belgium will use nanobodies, tiny fragments of antibodies and turn them into fluorescent polypeptides. Using a novel method called photoporation (pioneered by prof. Kevin Braeckmans at Ghent university), these nanobodies will be delivered into cells. We will obtain the most detailed information of an invadopodium that are currently attainable with state of the art technologies. The information obtained is relevant to how these structures are regulated and built up and will lead to potential applications and identification of new drug targets. The technological innovations in the project will advance our understanding of invadosomes to a level previously considered unattainable.