Rationally designed azobenzene photoswitches for efficient two-photon neuronal excitation

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Feb. 22, 2019

Manipulation of neuronal activity using two-photon excitation azobenzene photoswitches with near-infrared light has been recently demonstrated, but their practical use in tissue to photostimulate individual neurons three-dimensional precision hampered by firstly, the low efficacy and reliability NIR-induced photoisomerization compared one-photon excitation, secondly, short cis state lifetime responsive azo switches. Here we report rational design based on theoretical calculations synthesis endowed both high absorption cross section slow thermal back-isomerization. These compounds provide optimized sustained stimulation light-scattering brain Caenorhabditis elegans nematodes, displaying photoresponse intensities that are comparable those achieved under excitation. This finding opens way genetically targeted pharmacologically selective dissect intact circuits three dimensions.

Language: Английский

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Light-activated protein interaction with high spatial subcellular confinement

Proceedings of the National Academy of Sciences, Journal Year: 2018, Volume and Issue: 115(10)

Published: Feb. 20, 2018

Significance Inducible protein dimerization methods are powerful tools for the investigation of function. Unlike chemical systems, light-dependent systems can trigger at cellular and subcellular resolution. Here, we present a systematic comparison ability three blue-light-dependent tools, Cry2/CIB1, iLID, Magnets, to confine small volumes. Our study highlights parameters that contribute defining volume where dimer formation occurs, including switch-off kinetics photoreceptor(s). The highest confinement is achieved by Magnets iLID variants with very fast kinetics, although spatial resolution these comes expense total level dimers formed.

Language: Английский

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Near-Infrared Fluorescent Proteins: Multiplexing and Optogenetics across Scales

Trends in biotechnology, Journal Year: 2018, Volume and Issue: 36(12), P. 1230 - 1243

Published: July 23, 2018

Language: Английский

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Challenges for Therapeutic Applications of Opsin-Based Optogenetic Tools in Humans

Frontiers in Neural Circuits, Journal Year: 2020, Volume and Issue: 14

Published: July 15, 2020

As the technological hurdles are overcome and optogenetic techniques advance to have more control over neurons, therapies based on these approaches will begin emerge in clinic. Here we consider technical challenges surrounding transition of this breakthrough technology from an investigative tool a true therapeutic avenue. The emerging strategies remaining tasks genetically encoded molecules which respond light as well vehicles required deliver them discussed.The use optogenetics humans would represent completely new paradigm medicine be associated with unprecedented considerations. To applied for stimulation neurons humans, ideal need non-immunogenic, highly sensitive, activatable red or near-infrared (to maximize penetration while minimizing photodamage). enable sophisticated levels neuronal control, combined actuators indicators could closed-loop all-optical neuromodulation. Such systems introduce additional related spectral orthogonality between actuator indicator, decision making computational algorithms requirements large gene cassettes. any therapy, efficiency rely vector delivery expression appropriate cell type. Although viral vectors such those AAVs showing great potential human trials, barriers their general remain, including immune responses, delivery/transport, liver clearance. Limitations cassette size can packaged currently approved also addressed.

Language: Английский

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Good News for Nuclear Transgene Expression in Chlamydomonas

Cells, Journal Year: 2019, Volume and Issue: 8(12), P. 1534 - 1534

Published: Nov. 28, 2019

Chlamydomonasreinhardtii is a well-established model system for basic research questions ranging from photosynthesis and organelle biogenesis, to the biology of cilia basal bodies, channelrhodopsins photoreceptors. More recently, Chlamydomonas has also been recognized as suitable host production high-value chemicals recombinant proteins. However, applied have suffered inefficient expression nuclear transgenes. The combined efforts community over past decades provided insights into mechanisms underlying this phenomenon resulted in mutant strains defective some silencing mechanisms. Moreover, many gained parameters that affect transgene expression, like promoters, introns, codon usage, or terminators. Here I critically review these try integrate them design suggestions construction transgenes are be expressed at high levels.

Language: Английский

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Branched Photoswitchable Tethered Ligands Enable Ultra-efficient Optical Control and Detection of G Protein-Coupled Receptors In Vivo

Neuron, Journal Year: 2019, Volume and Issue: 105(3), P. 446 - 463.e13

Published: Nov. 26, 2019

Language: Английский

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A photoswitchable GPCR-based opsin for presynaptic inhibition

Neuron, Journal Year: 2021, Volume and Issue: 109(11), P. 1791 - 1809.e11

Published: May 11, 2021

Language: Английский

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Optogenetics at the presynapse

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(8), P. 984 - 998

Published: July 14, 2022

Language: Английский

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New insights into the molecular mechanisms of axon guidance receptor regulation and signaling

Current topics in developmental biology/Current Topics in Developmental Biology, Journal Year: 2021, Volume and Issue: unknown, P. 147 - 196

Published: Jan. 1, 2021

Language: Английский

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Intravital imaging to study cancer progression and metastasis

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 23(1), P. 25 - 42

Published: Nov. 16, 2022

Language: Английский

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