Lay summary
Advances in disease modelling and cell-based therapies hinge on precisely controlling which cells are eliminated and which are protected. However, in some scenarios current technologies struggle to 1) ablate specific cell types to model diseases marked by cell loss, or 2) keep therapeutic cells alive post-infusion into patients. This project aims to address these issues by discovering and fine-tuning enzymes–tiny biological machines–that act as programmable “switches”. To ablate cells, enzymes will be engineered to become prodrug-triggered self-destruct systems, eliminating targets with pinpoint accuracy so scientists can model diseases, map cellular regeneration, or destroy unwanted tissues. Companion enzymes will be engineered to make non-target cells drug-resistant, improving the precision of cellular elimination in disease modelling, or enhancing the survival of therapeutic cells when administered alongside chemotherapies. By developing versatile enzymatic tools to control cell fate, I aim to advance both the understanding and treatment of human disease.