Type I interferon (IFN) signalling is integral to eliminating infections and cancer in the human immune response. Conventional signalling requires the binding of IFN to both transmembrane receptor subunits, IFNAR1 and IFNAR2, to activate the classical JAK-STAT pathway for immune signalling. Our lab recently demonstrated that IFNβ is able to bind to the IFNAR1 subunit in the absence of IFNAR2 and activate STAT independent signalling. Activation of this pathway has been shown to rescue IFNAR2-/- mice from lipopolysaccharide-induced septic shock and reduce neuronal cell death in ischaemic stroke models. This project aims to characterise this novel, non-canonical IFN pathway at the molecular, cellular, tissue, and systemic levels in order to better understand its activation and involvement in pathogenesis. We will use super-resolution imaging to visualise IFNAR complex formation at the cell surface to understand signal initiation and regulation. IFNAR2-/- mice will be used to study the physiological implications of non-canonical signalling. To investigate whether this novel pathway exists in a natural setting, flow cytometry and immunohistochemistry will be used to establish the distribution of IFNAR1 and IFNAR2 on different human cell types and tissues. The knowledge gained will provide insight into a novel IFN signalling pathway with the potential to lead to treatments for its associated pathologies.