Steering Molecular Activity with Optogenetics: Recent Advances and Perspectives DOI

Teak‐Jung Oh,

Huaxun Fan, Savanna S. Skeeters

et al.

Advanced Biology, Journal Year: 2021, Volume and Issue: 5(5)

Published: Jan. 14, 2021

Optogenetics utilizes photosensitive proteins to manipulate the localization and interaction of molecules in living cells. Because light can be rapidly switched conveniently confined sub-micrometer scale, optogenetics allows for controlling cellular events with an unprecedented resolution time space. The past decade has witnessed enormous progress field within biological sciences. ever-increasing amount optogenetic tools, however, overwhelm selection appropriate strategies. Considering that each tool may have a distinct mode action, comparative analysis current toolbox promote further use optogenetics, especially by researchers new this field. This review provides such compilation highlights spatiotemporal accuracy systems. Recent advances live cells animal models are summarized, emerging work interlinks other research fields is presented, exciting clinical industrial efforts employ strategy toward disease intervention reported.

Language: Английский

Intracellular mRNA transport and localized translation DOI
Sulagna Das, Mariá Vera, Valentina Gandin

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 22(7), P. 483 - 504

Published: April 9, 2021

Language: Английский

Citations

272
Nucleated transcriptional condensates amplify gene expression DOI

Ming‐Tzo Wei,

Yi-Che Chang,

Shunsuke F. Shimobayashi

et al.

Nature Cell Biology, Journal Year: 2020, Volume and Issue: 22(10), P. 1187 - 1196

Published: Sept. 14, 2020

Language: Английский

Citations

258
Spatially Selective Imaging of Mitochondrial MicroRNAs via Optically Programmable Strand Displacement Reactions DOI
Jian Zhao, Zhixiang Li,

Yulei Shao

et al.

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(33), P. 17937 - 17941

Published: June 12, 2021

Abstract MicroRNA (miRNA) functions are tightly regulated by their sub‐compartmental location in living cells, and the ability to imaging of mitochondrial miRNAs (mitomiRs) is essential for understanding related pathological processes. However, most existing DNA‐based methods could not be used this purpose. Here, we report development a DNA nanoreporter technology mitomiRs cells through near‐infrared (NIR) light‐controlled strand displacement reactions. The sensing function nanoreporters silent (OFF) during delivery process, but can photoactivated (ON) with NIR light after targeted localization, enabling spatially‐restricted two types cancer‐related improved detection accuracy. Furthermore, demonstrate vivo spatiotemporally‐controlled activation. Therefore, study illustrates simple methodology that may broadly applicable investigating mitomiRs‐associated physiological events.

Language: Английский

Citations

107
A rapid inducible RNA decay system reveals fast mRNA decay in P-bodies DOI Creative Commons
Lauren A. Blake, Leslie Watkins, Yang Liu

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 28, 2024

Abstract RNA decay is vital for regulating mRNA abundance and gene expression. Existing technologies lack the spatiotemporal precision or transcript specificity to capture stochastic transient process. We devise a general strategy inducibly recruit protein factors modulate target metabolism. Specifically, we introduce Rapid Inducible Decay of (RIDR) technology degrade mRNAs within minutes. The fast synchronous induction enables direct visualization dynamics in cells. Applying RIDR endogenous ACTB reveals rapid formation dissolution granules pre-existing P-bodies. Time-resolved distribution measurements demonstrate inside P-bodies, which further supported by knocking down P-body constituent proteins. Light oxidative stress behavior, potentially reconciling contradictory literature about function. This study compartmentalized kinetics, establishing as pivotal tool exploring metabolism

Language: Английский

Citations

19
Synthetic Protein Condensates That Inducibly Recruit and Release Protein Activity in Living Cells DOI
Masaru Yoshikawa, Tatsuyuki Yoshii,

Masahiro Ikuta

et al.

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(17), P. 6434 - 6446

Published: April 23, 2021

Compartmentation of proteins into biomolecular condensates or membraneless organelles formed by phase separation is an emerging principle for the regulation cellular processes. Creating synthetic that accommodate specific intracellular on demand would have various applications in chemical biology, cell engineering, and biology. Here, we report construction protein capable recruiting and/or releasing interest living mammalian cells response to a small molecule light. By modular combination tandem fusion two oligomeric proteins, which forms phase-separated cells, with chemically induced dimerization tool, first created chemogenetic condensate system can rapidly recruit target from cytoplasm addition small-molecule dimerizer. We next coupled protein-recruiting engineered proximity-dependent protease, gave second wherein previously expressed inside are released small-molecule-triggered protease recruitment. Furthermore, optogenetic allows reversible release sequestration activity repeatable manner using light was constructed successfully. These systems were applicable control processes such as membrane ruffling ERK signaling time scale minutes. This proof-of-principle work provides new platform represents step toward tailor-made engineering condensate-based soft materials functionalities biological biomedical applications.

Language: Английский

Citations

69
Microscopic Imaging Techniques for Molecular Assemblies: Electron, Atomic Force, and Confocal Microscopies DOI
Ryou Kubota, Wataru Tanaka, Itaru Hamachi

et al.

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(22), P. 14281 - 14347

Published: May 4, 2021

Self-assembly is promising for construction of a wide variety supramolecular assemblies, whose 1D/2D/3D structures are typically relevant to their functions. In-depth understanding structure–function relationships essential rational design and development functional molecular assemblies. Microscopic imaging has been used as powerful tool elucidate individual assemblies with subnanometer millimeter resolution, which complementary conventional spectroscopic techniques that provide the ensemble structural information. In this review, we highlight representative examples visualization by use electron microscopy, atomic force confocal super-resolution microscopy. This review comprehensively describes nanofibers/gels, micelles/vesicles, coacervate droplets, polymer protein/DNA Advanced can address key challenges, like evaluation dynamics multicomponent self-assembly, self-assembly/disassembly in complex cellular milieu, also discussed. We believe would guidelines deeper analyses develop next-generation materials.

Language: Английский

Citations

57
Opportunities and challenges in cardiac tissue engineering from an analysis of two decades of advances DOI
Richard Z. Zhuang,

Roberta I. Lock,

Bohao Liu

et al.

Nature Biomedical Engineering, Journal Year: 2022, Volume and Issue: 6(4), P. 327 - 338

Published: April 27, 2022

Language: Английский

Citations

56
Optogenetics for transcriptional programming and genetic engineering DOI

Tien‐Hung Lan,

Lian He, Yun Huang

et al.

Trends in Genetics, Journal Year: 2022, Volume and Issue: 38(12), P. 1253 - 1270

Published: June 20, 2022

Language: Английский

Citations

47
Enzyme-Free Dynamic DNA Reaction Networks for On-Demand Bioanalysis and Bioimaging DOI
Shizhen He,

Jinhua Shang,

Yuqiu He

et al.

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 25, 2024

ConspectusThe pursuit of in-depth studying the nature and law life activity has been dominating current research fields, ranging from fundamental biological studies to applications that concern synthetic biology, bioanalysis, clinical diagnosis. Motivated by this intention, spatiotemporally controlled in situ analysis living cells a prospective branch virtue high-sensitivity imaging key biomolecules, such as biomarkers. The past decades have attested deoxyribonucleic acid (DNA), with biocompatibility, programmability, customizable features, is competitive biomaterial for constructing high-performance molecular sensing tools. To conquer complexity wide extracellular–intracellular distribution biomarkers, it meaningful breakthrough explore high-efficiently amplified DNA circuits, which excel at operating complex yet captivating dynamic reaction networks various bioapplications. In parallel, multidimensional performance improvements nucleic including availability, detection sensitivity, reliability, are critical parameters realizing accurate cell regulation bioanalysis.In Account, we summarize our recent work on enzyme-free bioanalysis three main aspects: circuitry functional extension recognition epigenetic regulation, amplification ability improvement sensitive biomarker detection, site-specific activation systems reliable imaging. first part, designed an epigenetically responsive deoxyribozyme (DNAzyme) system intracellular gene enriches possible analyzed species chemically modifying conventional DNAzyme. For example, exquisite N6-methyladenine (m6A)-caged DNAzyme was built achieving precise FTO (fat mass obesity-associated protein)-directed regulation. addition, varieties DNAzyme-based nanoplatforms self-sufficient cofactor suppliers were assembled, subdued speed-limiting hardness cofactors live-cell applications. second developed series hierarchically assembled improve signal transduction traditional circuits. First, circuit significantly enhanced via several heterogeneously or homogeneously concatenated models. Furthermore, feedback pathway integrated into these thus dramatically increasing efficiency. Second, considering cellular environment, simplified redundancy multicomponents procedures cascaded relying minimal component merely one modular catalytic reaction, guaranteed high cell-delivering uniformity while fostering kinetics reliability. third constructed in-cell-selective endogenous-stimulated multiply recognitions, could not only eliminate leakage, but also retain its on-site multiplex amplification. Based strategy, more availability scenarios acquired These demonstrate purpose-to-concreteness engineering tailored multimolecule multiple amplification, high-gain high-reliability targeted bioanalysis. We envision network can contribute bioanalytical layouts, will facilitate progression diagnosis prognosis.

Language: Английский

Citations

11
Using an ER-specific optogenetic mechanostimulator to understand the mechanosensitivity of the endoplasmic reticulum DOI Creative Commons
Yutong Song, Zhihao Zhao,

Linyu Xu

et al.

Developmental Cell, Journal Year: 2024, Volume and Issue: 59(11), P. 1396 - 1409.e5

Published: April 2, 2024

The ability of cells to perceive and respond mechanical cues is essential for numerous biological activities. Emerging evidence indicates important contributions organelles cellular mechanosensitivity mechanotransduction. However, whether how the endoplasmic reticulum (ER) senses reacts forces remains elusive. To fill knowledge gap, after developing a light-inducible ER-specific mechanostimulator (LIMER), we identify that mechanostimulation ER elicits transient, rapid efflux Ca2+ from in monkey kidney COS-7 cells, which dependent on cation channels transient receptor potential channel, subfamily V, member 1 (TRPV1) polycystin-2 (PKD2) an additive manner. This release can be repeatedly stimulated tuned by varying intensity duration force application. Moreover, inhibits ER-to-Golgi trafficking. Sustained mechanostimuli increase levels binding-immunoglobulin protein (BiP) expression phosphorylated eIF2α, two markers stress. Our results provide direct tight mechanoregulation functions, placing as player intricate map

Language: Английский

Citations

11