Project 466962

Broadly speaking, cancers are diseases stemming from mutations which cause abnormal cell growth, movement and behaviour. About a quarter of human cancers are driven by mutations in genes encoding Ras GTPase (Ras) proteins, leading to elevated activity and loss of control over processes that they normally regulate. Historically, Ras mutants have been near-impossible to treat because of their structure and efficiency in hyperactive states, but recent advances across diverse research fields have coalesced to reveal intriguing springboards for future therapies. Several bacterial toxins can permanently shut down Ras activity in human cells, and the past few years have seen the introduction of powerful tools and techniques that allow us to change the functions of proteins and toxins through artificial evolution. This project involves the use of a pipeline to completely redirect toxin activity from normal Ras to any mutated Ras of interest. The goal is to advance our understanding of such toxin-target interactions, and to exploit novel protein engineering strategies to generate toxins which specifically target disease-associated Ras mutants.