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

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 optimised
for 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