Molecular oxygen (O ₂ ) is a vital biological resource, delivery of which is impaired in many diseases due to inadequate blood perfusion. As a result, O ₂ deprivation (hypoxia) contributes to some of the leading causes of death and disability in developed countries, including stroke, ischemic heart disorders, and cancer. To help address these therapeutic challenges, the molecular mechanisms underpinning O ₂ homeostasis and hypoxic adaptation have been targeted to beneficially alter low O ₂ stress responses. Through this project you will characterise and develop inhibitors for a novel O ₂ sensing system, which acts through the N-degron pathway, and test their activity in relevant disease models.