Project No. 2439

STANDARD PROJECT

Primary Supervisor

Dr Jay R Laver – University of Southampton

Co-Supervisor(s)

Prof Daniel Mulvihill- University of Kent

Summary

The SARS-CoV-2 pandemic has highlighted the need for continued development of novel medical technologies.

Bacteria-based platform technologies for the delivery of biomolecules into the human body could conceivably underpin new and complement existing strategies for pandemic preparedness and prevention. The ability to cryopreserve bacteria into robust formulations enables dissemination of bacteria-based therapeutics beyond the end of the ‘cold chain’, with the potential to revolutionise access to medicines in many low and middle-income country (LMIC) settings.

Neisseria lactamica (Nlac) is a human-adapted, non-pathogenic Gram negative commensal of the upper respiratory tract. The Laver group’s proprietary technology for making targeted genetic change in this organism has led to the development of immunobiotic strains of genetically modified Nlac (GM-Nlac), which deliver surface-expressed anti-meningococcal vaccine antigens to the mucosal surface of the upper respiratory tract. Carriage of GM-Nlac has been shown to be safe, immunogenic, and long-lived. The Mulvihill group has recently demonstrated the utility of a proprietary vesicle nucleating peptide (vNP) technology for high level expression of heterologous proteins in E. coli, which are naturally and stably packaged into robust outer membrane vesicles. The aim of this project is to translate the vNP technology into GM-Nlac, and to design and generate a new platform technology for safe delivery of bacteria-synthesised biomolecules to the human respiratory mucosa.

The project will provide a comprehensive education in practical molecular microbiology, infection biology and immunology, including nucleic acid construct design and manipulation, aseptic technique and microbial culture, recombinant protein synthesis and purification, and experimental design and assay development.

The project will require the use of immunoassays such as ELISA and flow cytometry. This project is intensively laboratory-based, so the ideal candidate will have had training or laboratory experience to at least an undergraduate level and have a keen interest in microbiology, infection biology, vaccinology, and/or synthetic biology.