The Governing Council of the University of Toronto
Engineering genetic countermeasures against ionizing radiation a human iPSC-based model for targeting oxidative stress DNA damage and cellular senescence — This project will develop a robust human cell culture-based pipeline for engineering innate radiation protection mechanisms. As opposed to traditional models which lack biological relevance, this proposal leverages the use of hPSCs and derived cells thereof, constituting both a sensitive and relevant approach. The project will identify potential gene therapy targets that can confer radioprotective phenotypes by effectively reducing oxidative stress, DNA damage, and cell death responses whilst deepening our understanding of their underlying mechanisms. This approach could significantly advance efforts to protect human health in the challenging environment of space. The data generated herein is a potentially invaluable resource for the Canadian Space Agency and others for prediction of radiation resistance factors in living systems. Finally, this project will engineer gene therapy delivery vectors to demonstrate effective radiation protection in target cell culture models relevant for sp