Feng, J. et al. eLife 10.7554/eLife.10606 (29 December 2015).

Genetically encoded sensors for small molecules are useful for studying numerous biological processes, but general strategies for developing such sensors are lacking. Feng et al. now describe such an approach, based on protein destabilization. Their strategy begins with a protein that binds a target ligand. Mutations are introduced into this protein that destabilize the unbound form but not the ligand-bound form; thus, the protein accumulates only in the presence of ligand. This destabilized protein is then fused to a reporter such as a fluorescent protein or a transcription factor for readout. The team used their strategy to make sensors for digoxin and progesterone and showed that they work in multiple systems. They also demonstrated that their destabilized proteins can be used for ligand-dependent regulation of Cas9 genome editing activity.