The theme of our research is Innovating Protein Technologies for Therapeutics and Vaccine Design. We have a range of project areas running in the lab, from fundamental understanding of protein interactions and reactivity through to clinical application. The lab is also enthusiastic about entrepreneurship, supporting team members to create new concepts and develop the potential of their new technologies to tackle important challenges. Immuno-engineering and Global Health Developing an effective vaccine may be the most effective way to improve human health. The group has established a route to accelerate vaccine development, through our Plug-and-Protect platform. A limiting factor in vaccine generation is the difficulty of turning a promising target protein into the kind of assembly that would give long-lasting disease protection. We showed rapid and efficient decoration of virus-like particles, which elicited a strong immune response even with only a single injection. We demonstrated potent immunization towards the global health challenge of malaria, working with collaborators at Oxford University’s Jenner Institute. This approach is now being used by many groups against cancer and diverse infectious diseases, e.g. HIV, influenza, tuberculosis, and veterinary pathogens. Tag/Catcher vaccine technology has progressed to Phase 3 clinical trials for Covid-19, with clinical trials under way against malaria and CMV (a major cause of deafness and blindness in babies). Our current focus in this area is to create new protein antigen and nanoparticle strategies, to achieve broadly protective immune responses against targets that evade regular immune responses. We are working to establish new routes to general mucosal immunity, as well as to protect from gastric cancer. We have ongoing collaborations with Oxford, Caltech and the NIH, working towards protection against the most urgent global health challenges. Synthetic Biology and Click Biology from a New Generation of Protein Interactions We have harnessed an amazing feature of the surface of the pathogenic bacterium Streptococcus pyogenes, to create a family of protein superglues. This natural protein reactivity enabled us to form a spontaneous isopeptide bond between genetically-encoded protein and peptide partners. Our favourite pair, SpyTag/SpyCatcher, is one of the strongest protein interactions ever measured. SpyTag is now applied by more than a thousand labs around the world for diverse areas of basic research and biotechnology. The group also introduced the concept of Click Biology, to describe how easy-to-use genetically-encoded reactivity may empower a revolution in biological research, as happened in the physical sciences through Click Chemistry. We have now developed interactions tunable by pH and light. Combining computational design and evolution through phage display, we created the first genetically-encoded interaction reacting at the diffusion limit and approaching infinite affinity. We are extending this new class of protein interaction, to create unique new possibilities for synthetic biology. We are building a rainbow of protein superglues, to pattern interactions within cells and between cell-types. SpyTag provides unique opportunities for building resilient enzyme teams, for green biotransformation. Click Biology is a powerful tool to overcome challenges in gene therapy targeting and cancer evasion of cell therapy. SpyTag accelerates the creation of antibody teams for combinatorial control of cell signalling, for more potent targeting of cancer. We are now integrating protein binder assemblies with successful small molecule drugs, to achieve a new level of precision in control of cell fate and unveil new therapeutic possibilities. Vaccine development: Unique Protein Architectures and Chemical Biology for Cell Therapy Our studies defining the limits of cancer cell capture from blood made clear that even the best antibody interactions are not good enough. We have developed a new class of binding proteins that form covalent bonds to endogenous protein targets. NeissLock was engineered from an adhesion system from Neisseria meningitidis and forms an anhydride in response to calcium, reacting irreversibly with neighbouring proteins. Protein ligands that never let go of their targets should reduce the detection limit of soluble biomarkers for early diagnosis. We are progressing NeissLock technology to generate long-acting therapeutics through hitchhiking on red blood cells. We are also working to enhance CAR-T cell therapy of cancer, which has been revolutionary against leukaemia/lymphoma but has had little success against solid tumours. Get in contact for further information about any of these projects, or to discuss the possibility of working on other projects in the area of synthetic biology / vaccines / chemical biology / cancer.