What is the key to making unbreakable interactions between biomolecules and what impact can strong interactions have for studying and controlling cell function? To achieve covalent protein-protein interaction, Professor Howarth and his team have harnessed remarkable surface proteins from the human pathogen Streptococcus pyogenes. By rational engineering, they have generated a peptide (SpyTag) that spontaneously reacts to form an isopeptide bond to the protein partner (SpyCatcher). The reaction is high-yielding, genetically-encodable and shows specificity in cellular contexts.
They now have a set of bacterial superglues, to build multi-functional protein teams and tune surface receptor signalling on cancer cells and immune cells. The plug-and-play nature of this assembly is allowing exploration of new kinds of biological architectures and accelerating vaccine generation, including for malaria. Professor Howarth will also describe enhancing one of the strongest non-covalent interactions (streptavidin-biotin) for microscopy and how to achieve precise multi-fluorophore positioning to maximize both function and brightness.