Bioluminescence-driven optogenetics

Optogenetics utilizes light to activate genetically encoded light-sensing molecules. The light is delivered by optical materials, inserted into the brain, allowing millisecond precision in neuronal control. This temporally precise, but spatially restricted and invasive modulation by physical light sources can be complemented by combining optogenetic elements with “biological“ light sources. To this end we are tethering to the opsin a luciferase which produces light, bioluminescence, in the presence of a diffusible substrate, generating a luminescent opsin (luminopsin, LMO). Using luciferase-generated “biological“ light to activate optogenetic elements opens the entire optogenetic toolbox for complementation by a chemogenetic dimension while preserving the unique features of opsins. Matching the continuously evolving palette of opsins we are developing luciferases with improved light emission and shifted wavelengths. Moreover, we are taking advantage of both components, light emission and light sensing, being genetically encoded. Conceptually, this allows to combine a calcium-dependent luciferase with activating or silencing opsins, opening the door for all-molecular activity-regulated neuronal feedback. It also might allow regulation of neuronal activity through an 'optical synapse' when light emitting and light sensing moieties are arranged pre- and post-synaptically. In conclusion, biologically produced light through luciferases to activate optogenetic elements allows unprecedented versatility in controlling neuronal activity.