Teaching bacteria to recognize new molecules

Microbes can be engineered for different applications in our daily life, such as microbiome therapeutics, diagnosis of disease, or environmental monitoring. However, these applications are all based on the abilities of microbes to recognize and respond to novel signals such as disease biomarkers or environmental pollutants.

Here the members of the synthetic biology group at the CBS have developed a general framework to build synthetic receptors for bacteria to respond to novel ligands. The synthetic receptors are composed of: 1) The VHH camelid antibody which has shown the potential to recognize arbitrary targets; and 2) bacterial transcription factors which are responsible for controlling bacteria behavior. Once the synthetic receptors are activated by ligand-induced receptor dimerization, they can control bacteria response by changing gene expression. We provide a method to optimize receptor behavior by finely tuning protein expression levels and optimizing inter-domains linker regions. Finally, we show that these receptors can be connected to downstream synthetic gene circuits for further signal processing. The general nature of this platform and the versatility of antibody-based detection should support the deployment of these receptors into various hosts to detect ligands for which no receptor is found in nature.

For more details, please see our latest publication in ACS synthetic biology:
"A Modular Receptor Platform To Expand the Sensing Repertoire of Bacteria".