Decoding and recoding cellular signalling by protein loop replacement

Cells communicate with each other via complex chains of signalling events in which individual post-translational modifications of one protein stimulate modification of the next protein in a chain. Individual proteins can be modified combinatorially leading to an exquisite variety to subtly different responses. Understanding and reengineering these responses requires us to understand how each combination of modifications leads to the subsequent response. In this project, you will exemplify a new approach to protein engineering, generating specifically modified enzymes, characterising their resulting biochemistry and introducing them to cell to interrogate the cellular consequences of directly re-wiring the signalling pathways. The project will take advantage of new approaches for chemoenzymatic protein modification and will combine engineering biology approaches based on a combination of organic synthesis and computational protein structure prediction and design.