Lay summary
Numerous research teams around New Zealand employ targeted cellular ablation models to study physiology and degenerative disease. Many of these models are flawed, exhibiting confounding off-target toxicities, insufficient killing of target cells, or both. We have engineered a prodrug converting enzyme to be 100-fold more effective in activating a cytotoxin in vivo, and have shown this enables efficient and specific ablation of target cells in zebrafish models. We have also developed an unprecedented system for selective ablation of different tissues in the same animal. We now seek to make these tools available to New Zealand researchers in diverse animal models. By generating new models for them, we will eliminate the time and cost barrier that disincentivises creation and testing of new models; prove our system in direct head-to-head comparisons; foster the responsible use of more effective and relevant animal models; and ultimately transform the quality of biomedical research in New Zealand.