Transforming spatial and structural biology: Native ambient mass spectrometry (360G-Wellcome-305669_Z_23_Z)

Native ambient mass spectrometry (NAMS) is a novel tool, pioneered by our laboratory, which allows detection, identification and imaging of intact proteins in their native state directly from their physiological environment, i.e., from tissue. NAMS is an innovative approach which enables label-free in situ structural characterisation and spatial mapping (imaging) of folded proteins, protein assemblies, and protein-ligand (including protein-drug) complexes. It affords significant advantages over techniques such as immunohistochemistry as it enables spatially-resolved interrogation of protein interactions without the need for any prior knowledge of the proteins involved. NAMS offers unprecedented potential for integration of spatial and structural biology, and therefore promises to revolutionise the understanding of human health. The aim of this proposal is to transform NAMS from an emerging technology to the gold standard for integrated structural and spatial biology by addressing the key challenges of sensitivity and high-confidence protein identification, and thus delivering major advances in two key application areas: molecular pathology and drug discovery.