G protein coupled receptors (GPCRs) are the biological "inbox" of the cell. Residing in the cell membrane, they receive external chemical messages with exquisite sensitivity, and relay that message with chemical signals to the inside of the cell. This affects which genes are expressed and allow the cell to adapt and respond to its cellular environment. Using the tools of synthetic biology, it has now become possible to engineer cells like the humble bakers yeast with GPCRs from other organisms, so that the yeast becomes a specific and sensitive biosensor for a particular chemical. With cheap synthetic DNA that can be quickly assembled into bigger pieces like Lego, and genetic engineering tools like CRISPR/Cas9, the chemical relay can be hijacked, and directed to the expression of a reporter gene instead. A common choice is Green Fluorescent Protein (GFP), but something that can be seen with the naked eye, such as a brightly coloured pigment from coral, can also be used. In this way, yeast can be used to detect minute concentrations of a specific chemical. In 2020, my lab helped mentor a team of undergraduates as part of the Australian SynBio Challenge to design a diagnostic biosensor for Cryptococcus, an important human fungal pathogen that is the leading cause of death in AIDS patients. But this approach can also be used to detect and quantify almost any chemical that binds to a GPCR, from the pheromones of plant pathogens to illicit drugs. Do you have an idea for an inovative biosensor? Let's build it!
Shaw, W. M., Yamauchi, H., Mead, J., Gowers, G. O. F., Bell, D. J., Öling, D., Larsson, N., Wigglesworth, M., Ladds, G., & Ellis, T. (2019). Engineering a Model Cell for Rational Tuning of GPCR Signaling. Cell, 177(3), 782-796.e27. https://doi.org/10.1016/j.cell.2019.02.023