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Optogenetics

Controlling cellular activities with light

Nature Methods volume 20, pages 357–358 (2023)Cite this article

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New red–green optogenetic dimerizers enable the switching on and off of gene expression with high spatiotemporal precision.

Combining optics with genetic engineering (‘optogenetics’1) by using light-sensitive proteins to observe and control cellular activities has had important effects on cell biology and neuroscience. Light-sensitive proteins known as sensory photoreceptors are found throughout all kingdoms of life. These proteins contain a chromophore that undergoes transformation and/or formation of a chemical bond upon absorption of a photon, leading to a structural change in the photoreceptor that either causes an alteration of its own activity or is transduced to regulate the binding or activity of its effector. In the former case (for example, as with rhodopsins), the photoreceptor integrates both photosensory and effector functions as light-driven ion pumps. In the latter case (as with light–oxygen–voltage proteins, cryptochromes and phytochromes), the photoreceptor mediates intra- or intermolecular interactions with their respective effector domains in response to light2. These interactions influence the proximity of proteins and/or other biomolecules. As proximity is an essential regulatory factor in biological processes, optogenetic systems for light-induced proximity (also known as ‘dimerization’) in cells facilitate the rapid and reversible manipulation of highly dynamic cellular processes and have become valuable tools in diverse biological applications2,3.

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Fig. 1: BICYCL optogenetic systems for controlling gene expression.

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Acknowledgements

Y.-W.W. is supported by the European Research Council (ChemBioAP), Vetenskapsrådet (nr 2018-04585), the Knut and Alice Wallenberg Foundation and the Göran Gustafsson Foundation for Research in Natural Sciences and Medicine. The author thanks colleagues at Wu laboratory for discussion, and acknowledges D. Corkery for proofreading of the manuscript.

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  1. Department of Chemistry, Umeå University, Umeå, Sweden

    Yao-Wen Wu

  2. Umeå Centre for Microbial Research, Umeå University, Umeå, Sweden

    Yao-Wen Wu

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Correspondence to Yao-Wen Wu.

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Wu, YW. Controlling cellular activities with light. Nat Methods 20, 357–358 (2023). https://doi.org/10.1038/s41592-022-01745-3

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