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

Optogenetics and biosensors set the stage for metabolic cybergenetics DOI Creative Commons
César Carrasco‐López, Sergio A. García-Echauri, Therese Kichuk

et al.

Current Opinion in Biotechnology, Journal Year: 2020, Volume and Issue: 65, P. 296 - 309

Published: Sept. 12, 2020

Language: Английский

Citations

52
Heterogeneity, inherent and acquired drug resistance in patient-derived organoid models of primary liver cancer DOI

Linfeng Xian,

Pei Zhao, Xi Chen

et al.

Cellular Oncology, Journal Year: 2022, Volume and Issue: 45(5), P. 1019 - 1036

Published: Aug. 29, 2022

Language: Английский

Citations

37
Phase separation and pathologic transitions of RNP condensates in neurons: implications for amyotrophic lateral sclerosis, frontotemporal dementia and other neurodegenerative disorders DOI Creative Commons

Aditi Naskar,

Asima Nayak,

Muthu Raj Salaikumaran

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: Sept. 1, 2023

Liquid–liquid phase separation results in the formation of dynamic biomolecular condensates, also known as membrane-less organelles, that allow for assembly functional compartments and higher order structures within cells. Multivalent, reversible interactions between RNA-binding proteins (RBPs), including FUS, TDP-43, hnRNPA1, and/or RNA (e.g., RBP-RBP, RBP-RNA, RNA-RNA), result ribonucleoprotein (RNP) which are critical processing, mRNA transport, stability, stress granule assembly, translation. Stress granules, neuronal transport processing bodies examples cytoplasmic RNP while nucleolus Cajal representative nuclear condensates. In neurons, condensates promote long-range local translation dendrites axon, essential spatiotemporal regulation gene expression, axonal integrity synaptic function. Mutations RBPs pathologic mislocalization aggregation hallmarks several neurodegenerative diseases, amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease. ALS/FTD-linked mutations alter strength reversibility multivalent with other RNAs, resulting aberrant transitions. These have detrimental consequences on localization, translation, ultimately lead to compromised function Pathogenic protein is dependent various factors, dynamically arrested may serve an initial nucleation step aggregate formation. Recent studies focused identifying mechanisms by neurons resolve transitioned prevent pathogenic inclusions/aggregates. The present review focuses disease-linked RBPs, physiological functions role transitions disease, particularly ALS/FTD. We examine cellular contribute resolution potential therapeutic approaches aberrantly at a molecular level.

Language: Английский

Citations

21
Optogenetic control of mRNA condensation reveals an intimate link between condensate material properties and functions DOI Creative Commons
Min Woo Lee, Hyungseok C. Moon, Hyeonjeong Jeong

et al.

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

Published: April 15, 2024

Abstract Biomolecular condensates, often assembled through phase transition mechanisms, play key roles in organizing diverse cellular activities. The material properties of ranging from liquid droplets to solid-like glasses or gels, are features impacting the way resident components associate with one another. However, it remains unclear whether and how different would influence specific functions condensates. Here, we combine optogenetic control separation single-molecule mRNA imaging study relations between behaviors functional performance Using light-activated condensation, show that sequestering target mRNAs into condensates causes translation inhibition. Orthogonal reveals highly transient nature interactions individual Tuning condensate composition property towards more states leads stronger translational repression, concomitant a decrease molecular mobility. We further demonstrate β-actin sequestration neurons suppresses spine enlargement during chemically induced long-term potentiation. Our work highlights can modulate functions, mechanism may role fine-tuning output condensate-driven

Language: Английский

Citations

7
RNA N6-Methyladenosine and the Regulation of RNA Localization and Function in the Brain DOI
Sachithrani U. Madugalle, Kate D. Meyer,

Dan Ohtan Wang

et al.

Trends in Neurosciences, Journal Year: 2020, Volume and Issue: 43(12), P. 1011 - 1023

Published: Oct. 8, 2020

Language: Английский

Citations

45
From cradle to grave: neurogenesis, neuroregeneration and neurodegeneration in Alzheimer’s and Parkinson’s diseases DOI Creative Commons
Debia Wakhloo, Sameehan Mahajani, Jane Oberhauser

et al.

Neural Regeneration Research, Journal Year: 2022, Volume and Issue: 17(12), P. 2606 - 2606

Published: Jan. 1, 2022

Two of the most common neurodegenerative disorders – Alzheimer's and Parkinson's diseases are characterized by synaptic dysfunction degeneration that culminate in neuronal loss due to abnormal protein accumulation. The intracellular aggregation hyper-phosphorylated tau extracellular amyloid beta plaques form basis disease pathology. major hallmark is dopaminergic neurons substantia nigra pars compacta, following formation Lewy bodies, which consists primarily alpha-synuclein aggregates. However, discrete mechanisms contribute neurodegeneration these still poorly understood. Both impaired adult neurogenesis have been reported animal models disorders. Yet findings remain subject frequent debate a lack conclusive evidence post mortem brain tissue from human patients. While some publications provide significant related axonal regeneration diseases, they also highlight limitations obstacles development neuroregenerative therapies. In this review, we summarize vitro vivo neurogenesis, neuroregeneration context diseases.

Language: Английский

Citations

26
RAB13 mRNA compartmentalisation spatially orients tissue morphogenesis DOI Creative Commons
Guilherme Costa, Joshua J. Bradbury, Nawseen Tarannum

et al.

The EMBO Journal, Journal Year: 2020, Volume and Issue: 39(21)

Published: Sept. 18, 2020

Polarised targeting of diverse mRNAs to cellular protrusions is a hallmark cell migration. Although widespread phenomenon, definitive functions for endogenous targeted and their relevance modulation in vivo tissue dynamics remain elusive. Here, using single-molecule analysis, gene editing zebrafish live-cell imaging, we report that mRNA polarisation acts as molecular compass orients motile polarity spatially directs movement. Clustering protrusion-derived RNAseq datasets defined core 192-nt localisation element underpinning precise sites filopodia formation. Such the small GTPase RAB13 generated tight spatial coupling localisation, translation protein activity, achieving subcellular compartmentalisation function create polarised domain extension. Consequently, genomic excision this perturbation targeting-but not translation-depolarised endothelial cells induced mispatterning blood vessels zebrafish. Hence, polarisation, expression, primary determinant site action, preventing ectopic functionality at inappropriate loci orienting morphogenesis.

Language: Английский

Citations

31
Controlling gene expression with light: a multidisciplinary endeavour DOI Creative Commons
Denis Hartmann, Jefferson M. Smith, Giacomo Mazzotti

et al.

Biochemical Society Transactions, Journal Year: 2020, Volume and Issue: 48(4), P. 1645 - 1659

Published: July 13, 2020

The expression of a gene to protein is one the most vital biological processes. use light control biology offers unparalleled spatiotemporal resolution from an external, orthogonal signal. A variety methods have been developed that steps transcription and translation specific genes into proteins, for cell-free in vivo biotechnology applications. These employ techniques ranging modification small molecules, nucleic acids proteins with photocages, engineering involved using naturally light-sensitive proteins. Although majority currently available technologies ultraviolet light, there has recent increase functionalities work at longer wavelengths minimise cellular damage tissue penetration. Here, we discuss different chemical employed expression, while also highlighting central themes exciting applications within this diverse field.

Language: Английский

Citations

30
Programmable solid-state condensates for spatiotemporal control of mammalian gene expression DOI Creative Commons
Yukai Wang, Jian Jiang,

Qiqi Xiong

et al.

Nature Chemical Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

Engineering of nuclear condensates with chemically inducible gene switches is highly desired but challenging for precise and on-demand regulation mammalian expression. Here, we harness the phase-separation capability biomolecular describe a versatile strategy to program ligand-dependent expression at various stages interest. By engineering synthetic anchor proteins capable tethering genetically encoded condensate structures toward different cellular compartments or products interest, transcriptional translational activities was achieved endogenous episomal loci using same sets solid-state condensates. Using such holistic condensate-based strategy, not only performances comparing favorably state-of-the-art strategies described CRISPR–Cas9 activity silencing further showed that retention mRNA molecules into engineered within nucleus can become remarkably efficient alternative regulation. A ligand-responsive approach enables recruitment spatiotemporal control product release.

Language: Английский

Citations

0
Spatially Selective Imaging of Mitochondrial MicroRNAs via Optically Programmable Strand Displacement Reactions DOI
Jian Zhao, Zhixiang Li,

Yulei Shao

et al.

Angewandte Chemie, Journal Year: 2021, Volume and Issue: 133(33), P. 18081 - 18085

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

23