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Specifically, the project will use in vitro (2D cell lines, 3D spheroids and patient-derived organoids) and replacement in vivo (chick embryo) models of radioresistant tumours to characterise the molecular and cellular impact of ultra-high dose rate (FLASH) delivery of both protons and photons on normal versus tumour tissues, particularly in the context of DNA damage repair and survival pathways. This will also involve determining the critical proteins and pathways that mediate normal tissue sparing in comparison to conventional dose rate delivery. Research will utilise a FLASH photon system recently awarded through an MRC equipment grant, and FLASH protons delivered through the MC-40 cyclotron.