A Synthetic Biology Approach to Engineering Protein Assemblies for use in Vaccine Design

The emerging science of Bionanotechnology aims to use the principles of biological self-assembly, combined with structural and biochemical knowledge, to engineer nanoscale macromolecular structures with applications in medicine and related fields. Advances have been made recently in using heterologous, non-natural fusion proteins with engineered linkers that are capable of forming large, stable, multimeric assemblies. The development of such structures raises exciting possibilities for the design of regular assemblies which could be used as platforms for the display of multiple copies of antigens from an infectious bacterium. These assemblies would then be effective at eliciting a protective immune response, in a similar fashion to virus-like particles, which are already in widespread clinical use as vaccines. To design such a structure, express and isolate it, verify the assembly and demonstrate its effectiveness as a vaccine requires a range of skills, from computation and synthetic biology-based design, protein biochemistry, structural biology and immunology. This multidisciplinary project will examine the potential of this novel approach to develop a vaccine against meningococcal meningitis. This is a serious disease in developing and developed countries; attempts at control have met with only limited success, partly due to the considerable variation in surface protein antigens from serogroup B organisms from the causative bacterium, Neisseria meningitidis. Designed artificial assemblies, with incorporated meningitis antigens, will be designed, produced and tested for their ability to stimulate the production of antibodies which are capable of killing N. meningitidis. Ultimately, this approach could lead to a new way of developing vaccines.
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