Article
|
Open Access
Featured
-
-
Article
| Open AccessA modular tool to query and inducibly disrupt biomolecular condensates
Here, the authors present DisCo (Disassembly of Condensates), a method that allows the fast, inducible, and specific disruption of tagged condensates in mammalian cells. DisCo uses chemical dimerizers to induce the recruitment of a ligand into condensates leading to condensate disassembly.
- Carmen N. Hernández-Candia
- , Sarah Pearce
- & Chandra L. Tucker
-
Article
| Open AccessPhotoactivatable CaMKII induces synaptic plasticity in single synapses
Optogenetic control of molecules is important in cell biology and neuroscience. Here, the authors describe an optogenetic tool to control the Ca²+/calmodulin-dependent protein kinase II and use it to control plasticity at the single synapse level.
- Akihiro C. E. Shibata
- , Hiromi H. Ueda
- & Hideji Murakoshi
-
Article
| Open AccessA synthetic BRET-based optogenetic device for pulsatile transgene expression enabling glucose homeostasis in mice
Pulsing cellular dynamics in genetic circuits have been shown to provide critical capabilities to cells in diverse cellular activities. Here the authors show a synthetic BRET-based transgene expression system that allows pulsatile and quantitative activation of gene expression both in live cells and in vivo.
- Ting Li
- , Xianjun Chen
- & Yi Yang
-
Article
| Open AccessSoft subdermal implant capable of wireless battery charging and programmable controls for applications in optogenetics
Although wireless optogenetic technologies enable brain circuit investigation in freely moving animals, existing devices have limited their full potential, requiring special power setups. Here, the authors report fully implantable optogenetic systems that allow intervention-free wireless charging and controls for operation in any environment.
- Choong Yeon Kim
- , Min Jeong Ku
- & Jae-Woong Jeong
-
Article
| Open Access3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics
Currently technologies for monitoring and controlling neural activities in 3D models are lacking. Here the authors report a 3D high-density multielectrode array, with optical stimulation and drug delivery, to investigate neural circuit dynamics in engineered 3D neural tissues.
- Hyogeun Shin
- , Sohyeon Jeong
- & Il-Joo Cho
-
Article
| Open AccessEngineering of a bona fide light-operated calcium channel
Existing optogenetic methods to induce calcium mobilisation lack selectivity and specificity. Here, the authors design and engineer a single-component light-operated calcium channel to provide optical control over calcium signals and calcium-dependent physiological responses: LOCa.
- Lian He
- , Liuqing Wang
- & Yubin Zhou
-
Article
| Open AccessOrgan-specific, multimodal, wireless optoelectronics for high-throughput phenotyping of peripheral neural pathways
Advances in wireless technologies have enabled internalisation of light sources, but organ specific illumination is challenging. Here, the authors present a durable, multimodal, wireless system enabling optogenetic stimulation of peripheral neurons within organs.
- Woo Seok Kim
- , Sungcheol Hong
- & Sung Il Park
-
Article
| Open AccessSpatially expandable fiber-based probes as a multifunctional deep brain interface
Existing neural interfaces are limited in accessing one, small brain region. Here, the authors introduce a scaffold with helix hollow channels, which direct multisite multifunctional fibre probes into the brain at different angles, allowing for simultaneous recording and stimulation across distant regions.
- Shan Jiang
- , Dipan C. Patel
- & Xiaoting Jia
-
Article
| Open AccessBrainPhys neuronal medium optimized for imaging and optogenetics in vitro
Current media for neuronal cell and organoid cultures are suboptimal for functional imaging and optogenetics experiments, owing to phototoxicity and unphysiological performance. Here the authors formulate an optimised neuronal medium to support live cell imaging and electrophysiological activity.
- Michael Zabolocki
- , Kasandra McCormack
- & Cedric Bardy
-
Article
| Open AccessResonance energy transfer sensitises and monitors in situ switching of LOV2-based optogenetic actuators
Cellular optogenetics applications are limited by difficulties in quantification and blue light toxicity. Here the authors design LOV2-based switches that use resonance energy transfer to overcome these concerns.
- Li-Li Li
- , Florence M. Klein
- & Michael J. Courtney
-
Article
| Open AccessOptoribogenetic control of regulatory RNA molecules
Short hairpin RNAs can be used to modulate and regulate gene expression. Here the authors generate chimeric RNAs that interact with the photoreceptor PAL, allowing for optoribogenetic control of cell physiology.
- Sebastian Pilsl
- , Charles Morgan
- & Günter Mayer
-
Article
| Open AccessDevelopment of light-responsive protein binding in the monobody non-immunoglobulin scaffold
The ability to reversibly control monobody binding affinity would find use in biotechnology and research applications. Here the authors fuse the light-sensitive AsLOV2 domain to a monobody against the Abl SH2 domain to obtain a light dependent monobody and apply it in vitro and in mammalian cells.
- César Carrasco-López
- , Evan M. Zhao
- & José L. Avalos
-
Article
| Open AccessOptogenetic control of protein binding using light-switchable nanobodies
The ability to regulate nanobody affinity with light would expand the applications toolbox for these reagents. Here the authors insert an optimised photoswitchable AsLOV2 domain into multiple nanobodies and demonstrate photoswitchable binding to fluorescent proteins and endogenous proteins in cells.
- Agnieszka A. Gil
- , César Carrasco-López
- & Jared E. Toettcher
-
Article
| Open AccessExploiting natural chemical photosensitivity of anhydrotetracycline and tetracycline for dynamic and setpoint chemo-optogenetic control
Anhydrotetracycline and tetracycline are commonly used chemicals to regulate transcription and translation, respectively. Here the authors exploit the natural photosensitivity of these molecules to place their activity under optical control.
- Armin Baumschlager
- , Marc Rullan
- & Mustafa Khammash
-
Article
| Open AccessA non-invasive far-red light-induced split-Cre recombinase system for controllable genome engineering in mice
Current light-inducible Cre-loxP systems have minimal capacity for deep tissue penetration. Here, the authors present a far-red light-induced split Cre-loxP system for in vivo genome engineering.
- Jiali Wu
- , Meiyan Wang
- & Haifeng Ye
-
Article
| Open AccessLITESEC-T3SS - Light-controlled protein delivery into eukaryotic cells with high spatial and temporal resolution
The type III secretion system (T3SS) of bacteria can be used to inject cargo into eukaryotic cells but its lack of target specificity is a disadvantage. Here the authors place the T3SS under the regulation of light by engineering optogenetic switches into the dynamic cytosolic T3SS component SctQ.
- Florian Lindner
- , Bailey Milne-Davies
- & Andreas Diepold
-
Article
| Open AccessA Cdc42-mediated supracellular network drives polarized forces and Drosophila egg chamber extension
During development, organs undergo large scale forces driven by the cytoskeleton but the precise molecular regulation of cytoskeletal networks remains unclear. Here, the authors report a Cdc42-dependent supracellular cytoskeletal network integrates local actomyosin contraction at tissue scale and drives global tissue elongation.
- Anna Popkova
- , Orrin J. Stone
- & Xiaobo Wang
-
Article
| Open AccessCell-in-the-loop pattern formation with optogenetically emulated cell-to-cell signaling
Synthetic biological pattern formation is challenging to engineer due to theoretical complexity and practical limitations. Here, the authors introduce a cell-in-the-loop approach in which cells interact through in silico signaling.
- Melinda Liu Perkins
- , Dirk Benzinger
- & Mustafa Khammash
-
Article
| Open AccessOptogenetic manipulation of calcium signals in single T cells in vivo
The ability to manipulate and monitor calcium signaling in cells in vivo would provide insights into signaling in an endogenous context. Here the authors develop a two-photon-responsive calcium actuator and reporter combination to monitor the effect of calcium actuation on T cell migration, adhesion and chemokine release in vivo.
- Armelle Bohineust
- , Zacarias Garcia
- & Philippe Bousso
-
Article
| Open AccessOptogenetic regulation of endogenous proteins
Optogenetic approaches to control protein-protein interactions usually require overexpression of the target proteins. Here the authors integrate intrabodies into near-infrared- and blue-light activatable optogenetic tools to control endogenous proteins in mammalian cells.
- Taras A. Redchuk
- , Maksim M. Karasev
- & Vladislav V. Verkhusha
-
Article
| Open AccessNon-invasive optical control of endogenous Ca2+ channels in awake mice
Optogenetic applications in the brain of live animals often require the use of optic fibers due to poor tissue-penetration of blue light. Here the authors present monSTIM1, an improved high sensitivity optogenetic tool able to modulate Ca2+ signaling in the brain of awake mice using non-invasive light stimulation.
- Sungsoo Kim
- , Taeyoon Kyung
- & Won Do Heo
-
Article
| Open AccessMapping optogenetically-driven single-vessel fMRI with concurrent neuronal calcium recordings in the rat hippocampus
Detailed characterization of large-scale hemodynamic responses linked to specific neural activity remains to be elucidated at the single-vessel level across the subcentimeter scale hippocampal vasculature in vivo. Here, authors use a novel multi-modal fMRI platform to characterize distinct spatiotemporal patterns of hippocampal hemodynamic responses that were correlated to the optogenetically evoked Ca2+ events and to further demonstrate the significantly reduced neurovascular coupling efficiency upon spreading depression-like Ca2+ events.
- Xuming Chen
- , Filip Sobczak
- & Xin Yu
-
Article
| Open AccessOptical control of protein phosphatase function
Protein phosphatases play an essential role in signal transduction, but are understudied due to the difficulties in detecting phosphate removal and the lack of good inhibitors. Here the authors develop a light-activated protein phosphatase using photocaged, unnatural amino acids and use it to study ERK nuclear translocation.
- Taylor M. Courtney
- & Alexander Deiters
-
Article
| Open AccessPropagation of temporal and rate signals in cultured multilayer networks
The nature of the signals that propagate through feedforward networks is not well understood. Here, the authors combine microfabrication, multilayer cortical cultures, and optogenetic stimulation to show that NMDA-mediated synaptic current generates a sustained phase of activity that propagates firing rate signals.
- Jérémie Barral
- , Xiao-Jing Wang
- & Alex D. Reyes
-
Article
| Open AccessOptogenetic control of Bacillus subtilis gene expression
Bacillus subtilis has complex spatial and temporal gene expression patterns but currently lacks optogenetic tools to explore these processes. Here the authors import and debug a cyanobacterial green light sensor pathway and show that it enables precise optical control of gene expression.
- Sebastian M. Castillo-Hair
- , Elliot A. Baerman
- & Jeffrey J. Tabor
-
Article
| Open AccessA shape-memory and spiral light-emitting device for precise multisite stimulation of nerve bundles
Optogenetic stimulation of damaged peripheral nerves has advantages over electrical stimulation but it’s limited to single-site stimulation. Here the authors develop a spiral-shaped LED implant for precise optogenetic stimulation of peripheral nerve bundles at multiple sites and use it to induce distinct limb movements in mice.
- Hao Zheng
- , Zhitao Zhang
- & Jiayi Zhang
-
Article
| Open AccessMRI-guided robotic arm drives optogenetic fMRI with concurrent Ca2+ recording
Fiber optic implantation in deep areas of the rodent’s brain for MRI combined with optogenetics is challenging. Here the authors use an MRI-guided robotic arm as the navigation method for accurate fiber optic placement and precise microinjection during multi-modal fMRI, optogenetics and calcium recordings.
- Yi Chen
- , Patricia Pais-Roldan
- & Xin Yu
-
Article
| Open AccessReversible induction of mitophagy by an optogenetic bimodular system
Autophagic degradation of mitochondria (mitophagy) is a key quality control mechanism in cellular homeostasis, and its misregulation is involved in neurodegenerative diseases. Here the authors develop an optogenetic system for reversible induction of mitophagy and validate its use in cell culture and zebrafish embryos.
- Pasquale D’Acunzo
- , Flavie Strappazzon
- & Francesco Cecconi
-
Article
| Open AccessNeurotrophin receptor tyrosine kinases regulated with near-infrared light
Optical control over receptor tyrosine kinase (RTK) activity can find application in both basic biology and synthetic biology. Here the authors combine the photosensory module of DrBphP bacterial phytochrome with the Trk family of RTKs to obtain Trks that are reversibly switchable with near-infrared and far-red light.
- Anna V. Leopold
- , Konstantin G. Chernov
- & Vladislav V. Verkhusha
-
Article
| Open AccessOptogenetic dissection of Rac1 and Cdc42 gradient shaping
A steep gradient of Cdc42 is at the front of migrating cells, whereas the active Rac1 gradient is graded. Here the authors show that Cdc42 gradients follow the distribution of GEFs and govern direction of migration, while Rac1 gradients require the activity of the GAP β2-chimaerin and control cell speed.
- S. de Beco
- , K. Vaidžiulytė
- & M. Coppey
-
Article
| Open AccessIntegrating chemical and mechanical signals through dynamic coupling between cellular protrusions and pulsed ERK activation
Cellular ERK activation occurs as discrete pulses but their relationship to upstream Ras signaling is still under debate. Here, the authors show that Ras signaling associated with cellular protrusions triggers pulsed ERK activation, thereby enabling cells to integrate chemical and mechanical stimuli.
- Jr-Ming Yang
- , Sayak Bhattacharya
- & Chuan-Hsiang Huang
-
Article
| Open AccessPotassium channel-based optogenetic silencing
Optogenetic tools enable precise experimental control of the behaviour of cells. Here, the authors introduce a genetically-encoded two-protein system that enables silencing of excitable cells such as neurons and cardiomyocytes using blue light, and demonstrate its utility both in vitro and In vivo.
- Yinth Andrea Bernal Sierra
- , Benjamin R. Rost
- & Dietmar Schmitz
-
Article
| Open AccessComputational design of chemogenetic and optogenetic split proteins
Designing split protein approaches is time consuming and often results in high background activity due to spontaneous assembly. Here the authors present an automated approach which uses a split energy scoring function to identify optimal protein split sites and reduces spontaneous assembly.
- Onur Dagliyan
- , Andrey Krokhotin
- & Nikolay V. Dokholyan
-
Article
| Open AccessPulsatile inputs achieve tunable attenuation of gene expression variability and graded multi-gene regulation
Natural transcription factors are often regulated in a pulsatile fashion unlike many synthetic systems. Here the authors show that dynamic pulsatile signals reduce cell-to-cell gene expression variability in an optogenetic construct.
- Dirk Benzinger
- & Mustafa Khammash
-
Article
| Open AccessL-SCRaMbLE as a tool for light-controlled Cre-mediated recombination in yeast
The International Synthetic Yeast Sc2.0 project has built Cre recombinase sites into synthetic chromosomes, enabling rapid genome evolution. Here the authors demonstrate L-SCRaMbLE, a light-controlled recombinase tool with improved control over recombination events.
- Lena Hochrein
- , Leslie A. Mitchell
- & Bernd Mueller-Roeber
-
Article
| Open AccessOptical functionalization of human Class A orphan G-protein-coupled receptors
G-protein coupled receptors (GPCRs) represent the largest receptor family and are prime drug targets, but many orphan GPCRs are poorly characterized. Here authors engineer human orphan GPCRs to be activated by light which allows studying the receptors ligand identity and downstream signaling.
- Maurizio Morri
- , Inmaculada Sanchez-Romero
- & Harald Janovjak
-
Article
| Open AccessHigh frequency neural spiking and auditory signaling by ultrafast red-shifted optogenetics
Optogenetic applications would benefit from channelrhodopsins (ChRs) with faster photostimulation, increased tissue transparency and lower phototoxicity. Here, the authors develop fast red-shifted ChR variants and show the abilities for temporal precise spiking of cerebral interneurons and restoring auditory activity in deaf mice.
- Thomas Mager
- , David Lopez de la Morena
- & Ernst Bamberg
-
Article
| Open AccessActivity-dependent expression of Channelrhodopsin at neuronal synapses
Changes to subsets of dendritic spines are thought to be important for memory formation. Here, the authors develop a hybrid RNA/protein tool that allows for optogenetic stimulation of single synapses that have been tagged in an activity-dependent manner
- Francesco Gobbo
- , Laura Marchetti
- & Antonino Cattaneo
-
Article
| Open AccessShaping bacterial population behavior through computer-interfaced control of individual cells
Individual bacteria interact with each other and their environment to produce population-level patterns of gene expression. Here the authors use an automated platform combined with optogenetic feedback to manipulate population behaviors through dynamic control of individual cells.
- Remy Chait
- , Jakob Ruess
- & Călin C. Guet
-
Article
| Open AccessThree-dimensional scanless holographic optogenetics with temporal focusing (3D-SHOT)
Optogenetics, the optical stimulation of neurons, suffers from many technical challenges that limit the number of neurons that can be excited as well as their relative positions. Here, Pégard et al. develop a method to simultaneously stimulate an arbitrary number of neurons in 3D space with single neuron resolution.
- Nicolas C. Pégard
- , Alan R. Mardinly
- & Hillel Adesnik
-
Article
| Open AccessUnderstanding CRY2 interactions for optical control of intracellular signaling
Cryptochrome 2 (CRY2) can form light-regulated CRY2-CRY2 homo-oligomers or CRY2-CIB1 hetero-dimers, but modulating these interactions is difficult owing to the lack of interaction mechanism. Here the authors identify the interactions facilitating homo-oligomers and introduce mutations to create low and high oligomerization versions.
- Liting Duan
- , Jen Hope
- & Bianxiao Cui
-
Article
| Open AccessTimely regulated sorting from early to late endosomes is required to maintain cerebellar long-term depression
Long term depression (LTD) of the cerebellum is known to be mediated by postsynaptic trafficking of glutamate receptor AMPAR. Here, Kim and colleagues show that early- to late-endosomal sorting of AMPAR represents the switch from expression to maintenance phase of cerebellar LTD.
- Taegon Kim
- , Yukio Yamamoto
- & Keiko Tanaka-Yamamoto
-
Article
| Open AccessOptogenetic protein clustering through fluorescent protein tagging and extension of CRY2
Cryptochrome 2 (CRY2) from A. thaliana can be used to control light-dependent protein homo-oligomerization, but the molecular mechanism of CRY2 clustering is not known, limiting its application. Here the authors identify determinants of CRY2 clustering and engineer fusion partners to modulate clustering efficiency.
- Hyerim Park
- , Na Yeon Kim
- & Won Do Heo
-
Article
| Open AccessOptogenetic activation of Plexin-B1 reveals contact repulsion between osteoclasts and osteoblasts
Osteoclasts induce chemotaxis of osteoblasts during bone remodelling, but maintain spatial segregation. Here the authors show that osteoclasts repel osteoblasts via contact inhibition of locomotion mediated by Semaphorin-Plexin signalling and develop an optogenetic tool for Plexin-B1 to show how this signalling axis induces cell repolarization.
- Abhijit Deb Roy
- , Taofei Yin
- & Yi I. Wu
-
Article
| Open AccessThermogenetic neurostimulation with single-cell resolution
Current approaches to thermogenetic manipulation of neuronal activity lack sufficient spatiotemporal resolution. Here the authors show that neurons expressing snake TRPA1 channels are activated at high temporal resolution with IR light and this technique can be used to elicit behaviour in zebrafish larvae.
- Yulia G. Ermakova
- , Aleksandr A. Lanin
- & Vsevolod V. Belousov
-
Article
| Open AccessA simple optogenetic MAPK inhibitor design reveals resonance between transcription-regulating circuitry and temporally-encoded inputs
Light-sensitive regulators of protein kinases could offer valuable insights into intracellular signalling. Here the authors design an optogenetic inhibitor of c-Jun N-terminal kinase (JNK) and show evidence for resonance in JNK signalling circuits in neurons, and use the same design principle to develop an inhibitor for p38MAPK.
- Raquel M. Melero-Fernandez de Mera
- , Li-Li Li
- & Michael J. Courtney
-
Article
| Open AccessCell-matrix adhesion and cell-cell adhesion differentially control basal myosin oscillation and Drosophila egg chamber elongation
Pulsatile actomyosin contractility during tissue morphogenesis has been mainly studied in apical domains but less is known about the contribution of the basal domain. Here the authors show differential influence of cell-matrix and cell-cell adhesions in regulating oscillations and tissue elongation.
- Xiang Qin
- , Byung Ouk Park
- & Xiaobo Wang
-
Article
| Open AccessLayer-specific optogenetic activation of pyramidal neurons causes beta–gamma entrainment of neonatal networks
Oscillations in cortical activity during development are important for functional maturation. Here, the authors use optogenetics in neonatal mice to determine a causal role for pyramidal cell firing in different prelimbic cortex layers in generating beta–gamma range activity.
- Sebastian H Bitzenhofer
- , Joachim Ahlbeck
- & Ileana L. Hanganu-Opatz
-
Article
| Open AccessOptogenetic control of cellular forces and mechanotransduction
Cellular mechanical forces are regulated by Rho GTPases. Here the authors develop an optogenetic system to control the spatiotemporal activity of RhoA, and show that directing a RhoA activator to the plasma membrane causes contraction and YAP nuclear localization, whereas directing it to the mitochondria causes relaxation.
- Léo Valon
- , Ariadna Marín-Llauradó
- & Xavier Trepat