Towards translational optogenetics

Nature Biomedical Engineering, Journal Year: 2022, Volume and Issue: 7(4), P. 349 - 369

Published: Jan. 13, 2022

Language: Английский

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Activation of Wnt/β-catenin pathway mitigates blood–brain barrier dysfunction in Alzheimer’s disease

Brain, Journal Year: 2022, Volume and Issue: 145(12), P. 4474 - 4488

Published: July 5, 2022

Alzheimer's disease is a neurodegenerative disorder that causes age-dependent neurological and cognitive declines. The treatments for pose significant challenge, because the mechanisms of are not being fully understood. Malfunction blood-brain barrier increasingly recognized as major contributor to pathophysiology disease, especially at early stages disease. However, underlying remain poorly characterized, while few molecules can directly target improve function in context Here, we showed dysfunctional patients with reflected by perivascular accumulation blood-derived fibrinogen hippocampus cortex, accompanied decreased tight junction proteins Claudin-5 glucose transporter Glut-1 brain endothelial cells. In APPswe/PS1dE9 (APP/PS1) mouse model dysfunction started 4 months age became severe 9 age. cerebral microvessels APP/PS1 mice amyloid-β-treated cells, found suppressed Wnt/β-catenin signalling triggered an increase GSK3β activation, but inhibition AKT pathway or switching Wnt/planar cell polarity pathway. Furthermore, using our newly developed optogenetic tool controlled regulation LRP6 (upstream regulator Wnt signalling) activate pathway, malfunction was restored preventing amyloid-β-induced cells impairments promoting repair. conclusion, targeting endothelium alleviate induced amyloid-β, which may be potential treatment strategy

Language: Английский

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Optophysiology: Illuminating cell physiology with optogenetics

Physiological Reviews, Journal Year: 2022, Volume and Issue: 102(3), P. 1263 - 1325

Published: Jan. 24, 2022

Optogenetics combines light and genetics to enable precise control of living cells, tissues, organisms with tailored functions. has the advantages noninvasiveness, rapid responsiveness, tunable reversibility, superior spatiotemporal resolution. Following initial discovery microbial opsins as light-actuated ion channels, a plethora naturally occurring or engineered photoreceptors photosensitive domains that respond at varying wavelengths ushered in next chapter optogenetics. Through protein engineering synthetic biology approaches, genetically encoded photoswitches can be modularly into scaffolds host cells myriad biological processes, well behavioral disease intervention vivo. Here, we summarize these optogenetic tools on basis their fundamental photochemical properties better inform chemical design principles. We also highlight exemplary applications opsin-free optogenetics dissecting cellular physiology (designated "optophysiology") describe current progress, future trends, wireless optogenetics, which enables remote interrogation physiological processes minimal invasiveness. This review is anticipated spark novel thoughts next-generation devices promise accelerate both basic translational studies.

Language: Английский

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At Light Speed: Advances in Optogenetic Systems for Regulating Cell Signaling and Behavior

Annual Review of Chemical and Biomolecular Engineering, Journal Year: 2017, Volume and Issue: 8(1), P. 13 - 39

Published: June 7, 2017

Cells are bombarded by extrinsic signals that dynamically change in time and space. Such dynamic variations can exert profound effects on behaviors, including cellular signaling, organismal development, stem cell differentiation, normal tissue function, disease processes such as cancer. Although classical genetic tools well suited to introduce binary perturbations, new approaches have been necessary investigate how signal variation may regulate behavior. This fundamental question is increasingly being addressed with optogenetics, a field focused engineering harnessing light-sensitive proteins interface signaling pathways. Channelrhodopsins initially defined optogenetics; however, through recent use of light-responsive myriad spectral functional properties, practical applications optogenetics currently encompass subcellular localization, gene regulation. Now, important questions regarding integration within branch points networks, asymmetric responses spatially restricted signals, dosage versus duration be addressed. review summarizes emerging technologies the expanding optogenetics.

Language: Английский

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Remote Regulation of Membrane Channel Activity by Site‐Specific Localization of Lanthanide‐Doped Upconversion Nanocrystals

Angewandte Chemie International Edition, Journal Year: 2017, Volume and Issue: 56(11), P. 3031 - 3035

Published: Feb. 3, 2017

Abstract The spatiotemporal regulation of light‐gated ion channels is a powerful tool to study physiological pathways and develop personalized theranostic modalities. So far, most existing are limited by their action spectra in the ultraviolet (UV) or visible region. Simple innovative strategies for specific attachment photoswitches on cell surface without modifying genetically encoding channel structures, more importantly, that enable remote activation ion‐channel functions within near‐infrared (NIR) spectral window living systems, remain challenging concern. Herein, metabolic glycan biosynthesis used achieve site‐specific covalent near‐infrared‐light‐mediated lanthanide‐doped upconversion nanocrystals (UCNs) through copper‐free click cyclization. Upon irradiation with 808 nm light, converted emission at 480 could activate channel, channelrhodopsins‐2 (ChR2), thus remotely control cation influx. This unique strategy provides valuable insights membrane‐associated activities vivo.

Language: Английский

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Blue light-mediated transcriptional activation and repression of gene expression in bacteria

Nucleic Acids Research, Journal Year: 2016, Volume and Issue: 44(14), P. 6994 - 7005

Published: June 28, 2016

Light-regulated modules offer unprecedented new ways to control cellular behavior in precise spatial and temporal resolution. The availability of such tools may dramatically accelerate the progression synthetic biology applications. Nonetheless, current optogenetic toolbox prokaryotes has potential issues as lack rapid switchable control, less portable, low dynamic expression limited parts. To address these shortcomings, we have engineered a novel bidirectional promoter system for Escherichia coli that can be induced or repressed rapidly reversibly using blue light dependent DNA-binding protein EL222. We demonstrated by modulating dosage pulses intensity could level gene precisely. show both light-inducible repressible function parallel with high precision single cell switched stably between ON- OFF-states repetitive light. In addition, kinetics were quantitatively analysed mathematical model. further apply system, first time, optogenetically synchronize two receiver cells performing different logic behaviors over time molecular clock signal. Overall, our modular approach layers transformative platform next-generation light-controllable systems prokaryotes.

Language: Английский

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Near‐Infrared‐Light Activatable Nanoparticles for Deep‐Tissue‐Penetrating Wireless Optogenetics

Advanced Healthcare Materials, Journal Year: 2019, Volume and Issue: 8(6)

Published: Jan. 11, 2019

Abstract Optogenetics has been developed to control the activities and functions of cells with high spatiotemporal resolution, cell‐type specificity, flexibility. However, current optogenetic tools generally rely on visible light (e.g., blue or yellow) shallow tissue penetration ability that does require invasive fiber‐optic probes deliver into organs animal tissues. This often results in a series side effects, such as damage unwanted inflammation. Fortunately, emerging wireless can respond deep‐tissue‐penetrating near‐infrared (NIR) have attracted increasing attention due their much‐reduced living organisms. There are mainly two types NIR‐activatable tools: one uses lanthanide‐doped upconversion nanoparticles transduce NIR modulate classical opsin‐expressing neurons; other type couples an absorber convert heat activate thermosensitive proteins. These enable low‐invasive “remote control” activation inhibition cellular signaling pathways. approach great potential help create more innovative therapies for diseases like cancer, diabetes, neuronal disorders near future. Therefore, this review article summarizes recent advances design strategies synthetic methods nanomaterials applications.

Language: Английский

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Recent advances in the optical control of protein function through genetic code expansion

Current Opinion in Chemical Biology, Journal Year: 2018, Volume and Issue: 46, P. 99 - 107

Published: July 26, 2018

Language: Английский

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Photoreceptor engineering

Frontiers in Molecular Biosciences, Journal Year: 2015, Volume and Issue: 2

Published: June 17, 2015

Sensory photoreceptors not only control diverse adaptive responses in Nature, but as light-regulated actuators they also provide the foundation for optogenetics, non-invasive and spatiotemporally precise manipulation of cellular events by light. Novel have been engineered that establish light over manifold biological processes previously inaccessible to optogenetic intervention. Recently, photoreceptor engineering has witnessed a rapid development, perturbation plethora are now available. Here, we review fundamental principles allostery. Photoreceptors dichotomize into associating receptors alter their oligomeric state part allostery non-associating do not. A survey pinpoints association reactions order-disorder transitions particularly powerful versatile design principles. Photochromic bidirectionally toggled two colors augur enhanced spatiotemporal resolution use photoactivatable fluorophores. By identifying desirable traits photoreceptors, pointers future, actuators.

Language: Английский

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Reversible, Spatial and Temporal Control over Protein Activity Using Light

Trends in Biochemical Sciences, Journal Year: 2018, Volume and Issue: 43(8), P. 567 - 575

Published: June 19, 2018

Language: Английский

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