A novel synthetic biology approach towards anti-bacterial cell therapy

Synthetic biology applies the engineering principles of modularity and standardisation to construct new and improved biological systems. It strives to make the engineering of biology easier and more predictable, and already enables control over complex cellular behaviours in bacteria and yeast. The field is currently making great progress at extending this level of control to mammalian cells, bringing novel synthetic systems into the clinic.

By repurposing existing receptor architectures, we will develop novel signalling circuits in mammalian cells that endow them with artificial bacteria-sensing functions.

In the first instance, mammalian cells will be engineered to detect common lab strains like Escherichia coli or Bacillus subtilis as a proxy for infectious bacterial cells. Through iterative engineering rounds, clear design rules will be identified to ensure robust and specific detection. After this proof of concept stage and as a step further towards anti-bacterial cell therapy, mammalian cells will be engineered to detect pathogens such as Pseudomonas aeruginosa or Staphylococcus aureus.

If successful, further engineering could be envisaged to create seek-and-destroy cells that can assist in pathogen clearance and immune activation. Importantly, the pathogen-sensing cells engineered in this project might also be used to study the cellular interactions taking place between bacteria and host cells during bacterial infections.