Environmental cues regulate many biological processes, often initiated by sensory protein domains which use small molecule ligands to convert environmentally-triggered changes into altered protein/protein interactions. Several families of these domains have evolved with remarkable diversity in their inputs and outputs. Using a combination of biophysics, biochemistry and synthetic chemistry, we seek to gain insight into the mechanistic controls of such environmental sensing domains for both fundamental understanding and subsequent artificial control.
Here I will discuss examples of our work exploring how the Period-ARNT-Singleminded (PAS) and Light-Oxygen-Voltage (LOV) protein domains convert changes in biochemical stimuli into control of a wide range of output functions. Biophysical and biochemical studies of these proteins have given us the mechanistic understanding needed to develop the artificial regulation of such systems, both in vitro and in living cells. Taken together, our work provides an integrated view of a fascinating class of natural switches and has demonstrated routes by which these can be manipulated to achieve desired therapeutic and/or technological outcomes.