A systematic structural-based approach to studying protein interactions in the centriole/centrosome

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Centrosomes are required for cell division, cilia formation, cytoskeletal organisation and cell signalling, and their dysfunction leads to a range of human diseases, including cancer. Centrosomes are complicated structures comprising >400 proteins, but only a small, well-conserved, group of proteins are required for centrosome assembly. The protein interactions mediating assembly are mostly unknown. While previous work studying protein interactions has often relied on relatively slow and laborious techniques such as X-ray crystallography, recent advances allow for the much faster computational prediction of 3D interaction structures. Experimental work testing these predictions can then be targeted to specific interfaces.This project aims to identify and characterise interactions between the small set of core centrosome proteins required for centrosome assembly. Interactions will first be predicted computationally, and predictions scoring above a specified confidence threshold will be assessed experimentally. In parallel with this, various methods will be tested to develop a pipeline optimisedfor speed and accuracy of protein interaction prediction and validation.Overall, this work will increase our knowledge of the structural basis of interactions involved in centrosome assembly, as well as developing new methodology to enable this approach to be expanded to other candidate proteins involved in other biological processes.BBSRC priority areas: - Understanding the rules of life- Transformative technologies