The Rise of Optogenetics – Controlling Cells with Light

Photoswitches

Optogenetics is based on using proteins that can be found in nature and enable organisms to sense light. Essentially all plants and photosynthetic microorganisms as well as many bacteria are equipped with molecular sensors they use to determine light intensity, its direction, its composition, and things like the length of day. Many use this input to optimize their benefit from the exposure to light, for example by moving towards the light, adjusting their metabolism, or growth progression. These molecular light sensors can be isolated and transplanted into unrelated cells or organisms using genetic engineering.

The earliest broad application of using these sensors was established in the field of neuroscience. The first generation of optogenetic proteins were light-gated ion channels isolated from microscopic algae, which can induce ion currents across biological membranes upon exposure to certain wavelengths of light. This also works when they are genetically transplanted into animal cells. Thus, neurons that have been equipped with these proteins can be made to either fire or also to be inactive when exposed to light, depending on which form of protein is used. In recent years, the new principle of optogenetics with its unprecedented temporal and also spatial precision has become the gold standard to study cultured neurons and even certain aspects of brain function.

Unprecedented Opportunities for the Bio-Industry

Recently, the panel of optogenetic tools has been significantly expanded. By combining other proteins that confer different effector functions with the light sensors, photoswitch systems can be tailored to control a diversity of effects in living cells. In the meantime, this offers direct control of a broad spectrum of different physiological responses in living cells.

Many new sensor/effector combinations have been developed over the last years, several of them allowing the direct control of genes*. This repertoire now builds a solid basis to start controlling cells in very diverse ways, for example using them in new ways to produce advanced bio-molecules.

*De Mena et al., “Bringing Light to Transcription: The Optogenetics Repertoire”, Frontiers in Genetics 9, article 518, 2018