Ribosome mutant-induced Cell Competition: from mechanisms to identification of cancer vulnerabilities

Cells carrying a single faulty copy of a ribosome protein gene are actively killed off by their healthier neighbours—a process called Minute cell competition—and this project aims to turn that cellular quality-control mechanism against cancer. This matters because cancer cells often lose large chunks of their genomes, including ribosome protein genes, which should make them vulnerable to elimination. Yet tumours somehow survive. The gap in knowledge is exactly how Minute competition works in mammals, and whether the same stress signals that trigger it in flies—oxidative and proteotoxic stress—operate in human cells. The research has three concrete aims: first, to build mammalian cell competition assays and test whether oxidative stress drives loser status; second, to identify small-molecule drugs that can manipulate the Nrf2 stress-response pathway to force cancer cells into the loser role; third, to use human cancer genomics and fly genetics to understand how some tumours evade this elimination. If successful, this work could reveal a new class of cancer vulnerabilities—drugs that tip the balance of cell competition to make ribosome-mutant tumour cells lose against their normal neighbours. The project is fundamentally curiosity-driven, but the identification of drug-like modulators of cell competition could open a therapeutic avenue that exploits an ancient quality-control system.