Antioxidant Therapy in Parkinson’s Disease: Insights from Drosophila melanogaster DOI Creative Commons
Federica De Lazzari, Federica Sandrelli, Alexander J. Whitworth

et al.

Antioxidants, Journal Year: 2020, Volume and Issue: 9(1), P. 52 - 52

Published: Jan. 7, 2020

Reactive oxygen species (ROS) play an important role as endogenous mediators in several cellular signalling pathways. However, at high concentrations they can also exert deleterious effects by reacting with many macromolecules including DNA, proteins and lipids. The precise balance between ROS production their removal via numerous enzymatic nonenzymatic molecules is of fundamental importance for cell survival. Accordingly, neurodegenerative disorders, Parkinson’s disease (PD), are associated excessive levels ROS, which induce oxidative damage. With the aim coping progression PD, antioxidant compounds currently receiving increasing attention potential co-adjuvant treatment these diseases, studies have been performed to evaluate purported protective molecules. In present review, we discuss relevance use Drosophila melanogaster animal model therapeutic natural synthetic antioxidants. conservation most PD-related genes humans D. melanogaster, along animal’s rapid life cycle versatility genetic tools, makes fruit flies ideal experimental system screening antioxidant-based treatments.

Language: Английский

FlyBase: a guided tour of highlighted features DOI Creative Commons
L. Sian Gramates,

Julie Agapite,

Helen Attrill

et al.

Genetics, Journal Year: 2022, Volume and Issue: 220(4)

Published: March 10, 2022

FlyBase provides a centralized resource for the genetic and genomic data of Drosophila melanogaster. As enters our fourth decade service to research community, we reflect on unique aspects look forward continued collaboration with larger model organism communities. In this study, emphasize dedicated reports tools have constructed meet specialized needs fly researchers but also facilitate use by other We highlight ways that support including an external resources page, help resources, multiple avenues which can interact FlyBase.

Language: Английский

Citations

467
FlyBase: updates to theDrosophila melanogasterknowledge base DOI Creative Commons
Aoife Larkin, Steven J Marygold, Giulia Antonazzo

et al.

Nucleic Acids Research, Journal Year: 2020, Volume and Issue: 49(D1), P. D899 - D907

Published: Oct. 22, 2020

FlyBase (flybase.org) is an essential online database for researchers using Drosophila melanogaster as a model organism, facilitating access to diverse array of information that includes genetic, molecular, genomic and reagent resources. Here, we describe the introduction several new features at FlyBase, including Pathway Reports, paralog information, disease models based on orthology, customizable tables within reports overview displays ('ribbons') expression data. We also variety recent important updates, incorporation developmental proteome, upgrades GAL4 search tab, additional Experimental Tool migration JBrowse genome browsing improvements batch queries/downloads Fast-Track Your Paper tool.

Language: Английский

Citations

422
A large-scale resource for tissue-specific CRISPR mutagenesis in Drosophila DOI Creative Commons
Fillip Port,

Claudia Strein,

Mona Stricker

et al.

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Feb. 13, 2020

Genetic screens are powerful tools for the functional annotation of genomes. In context multicellular organisms, interrogation gene function is greatly facilitated by methods that allow spatial and temporal control abrogation. Here, we describe a large-scale transgenic short guide (sg) RNA library efficient CRISPR-based disruption specific target genes in constitutive or conditional manner. The consists currently more than 2600 plasmids 1700 fly lines with focus on targeting kinases, phosphatases transcription factors, each expressing two sgRNAs under Gal4/UAS system. We show CRISPR mutagenesis robust across many can be efficiently employed various somatic tissues, as well germline. order to prevent artefacts commonly associated excessive amounts Cas9 protein, have developed series novel UAS-Cas9 transgenes, which fine tuning expression achieve high editing activity without detectable toxicity. Functional assays, direct sequencing genomic sgRNA sites, indicates vast majority mediate disruption. Furthermore, conducted so far largest fully screen any metazoan organism, further supported efficiency accuracy our revealed uncharacterized essential development.

Language: Английский

Citations

147
Large-Scale Transgenic Drosophila Resource Collections for Loss- and Gain-of-Function Studies DOI Open Access
Jonathan Zirin, Yanhui Hu, Luping Liu

et al.

Genetics, Journal Year: 2020, Volume and Issue: 214(4), P. 755 - 767

Published: Feb. 19, 2020

The Transgenic RNAi Project (TRiP), a Drosophila melanogaster functional genomics platform at Harvard Medical School, was initiated in 2008 to generate and distribute genome-scale collection of RNA interference (RNAi) fly stocks. To date, it has generated >15,000 As this covers most genes, we have largely transitioned development new resources based on CRISPR technology. Here, present an update our libraries publicly available stocks, focus the TRiP-CRISPR overexpression (TRiP-OE) knockout (TRiP-KO) collections. TRiP-OE stocks express single guide RNAs targeting upstream gene transcription start site. Gene activation is triggered by coexpression catalytically dead Cas9 fused activator domain, either VP64-p65-Rta or Synergistic Activation Mediator. TRiP-KO one two coding sequence genes. Cutting Cas9, allowing for generation indels both germline somatic tissue. >5000 community. These provide versatile, transformative tools activation, repression, genome engineering.

Language: Английский

Citations

112
Precise genome engineering in Drosophila using prime editing DOI Open Access
Justin A. Bosch,

Gabriel Birchak,

Norbert Perrimon

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 118(1)

Published: Dec. 21, 2020

Precise genome editing is a valuable tool to study gene function in model organisms. Prime editing, precise system developed mammalian cells, does not require double-strand breaks or donor DNA and has low off-target effects. Here, we applied prime for the organism

Language: Английский

Citations

87
A versatile toolkit for CRISPR-Cas13-based RNA manipulation in Drosophila DOI Creative Commons
Nhan Huynh,

Noah Depner,

Raegan Larson

et al.

Genome biology, Journal Year: 2020, Volume and Issue: 21(1)

Published: Nov. 17, 2020

Abstract Advances in CRISPR technology have immensely improved our ability to manipulate nucleic acids, and the recent discovery of RNA-targeting endonuclease Cas13 adds even further functionality. Here, we show that works efficiently Drosophila , both ex vivo vivo. We test 44 different variants identify enzymes with best overall performance could target endogenous transcripts high efficiency specificity. also develop applications edit mRNAs mitochondrial transcripts. Our vector collection represents a versatile tool gene expression at post-transcriptional level.

Language: Английский

Citations

86
CRISPR screens in plants: approaches, guidelines, and future prospects DOI Open Access
Christophe Gaillochet, Ward Develtere, Thomas B. Jacobs

et al.

The Plant Cell, Journal Year: 2021, Volume and Issue: 33(4), P. 794 - 813

Published: April 1, 2021

Abstract Clustered regularly interspaced short palindromic repeat (CRISPR)-associated systems have revolutionized genome engineering by facilitating a wide range of targeted DNA perturbations. These resulted in the development powerful new screens to test gene functions at genomic scale. While there is tremendous potential map and interrogate regulatory networks unprecedented speed scale using CRISPR screens, their implementation plants remains its infancy. Here we discuss general concepts, tools, workflows for establishing analyze handful recent reports describing use this strategy generate mutant knockout collections or diversify sequences. In addition, provide insight into how design given current challenges limitations examine multiple options. Finally, unique multiplexing capabilities investigate redundant highly duplicated plant genomes. Combinatorial routinely higher-order facilitate characterization networks. By integrating approach with numerous profiles that been generated over past two decades, offers opportunities genomes deeper resolution will lead great advances functional synthetic biology.

Language: Английский

Citations

80
Molecular logic of synaptic diversity between Drosophila tonic and phasic motoneurons DOI Creative Commons

Suresh K. Jetti,

Andrés B. Crane, Yulia Akbergenova

et al.

Neuron, Journal Year: 2023, Volume and Issue: 111(22), P. 3554 - 3569.e7

Published: Aug. 22, 2023

Although neuronal subtypes display unique synaptic organization and function, the underlying transcriptional differences that establish these features are poorly understood. To identify molecular pathways contribute to diversity, single-neuron Patch-seq RNA profiling was performed on Drosophila tonic phasic glutamatergic motoneurons. Tonic motoneurons form weaker facilitating synapses onto single muscles, while stronger depressing multiple muscles. Super-resolution microscopy in vivo imaging demonstrated active zones more compact enhanced Ca2+ influx compared with their counterparts. Genetic analysis identified properties mapped gene expression for several cellular pathways, including distinct signaling ligands, post-translational modifications, intracellular buffers. These findings provide insights into how transcriptomes drive functional morphological between subtypes.

Language: Английский

Citations

32
Identification of secretory autophagy as a mechanism modulating activity-induced synaptic remodeling DOI
Yen-Ching Chang, Yuan Gao, Joo Yeun Lee

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(16)

Published: April 8, 2024

The ability of neurons to rapidly remodel their synaptic structure and strength in response neuronal activity is highly conserved across species crucial for complex brain functions. However, mechanisms required elicit coordinate the acute, activity-dependent structural changes synapses are not well understood, as neurodevelopment plasticity tightly linked. Here, using an RNAi screen Drosophila against genes affecting nervous system functions humans, we uncouple cellular processes important synapse development. We find mutations associated with neurodegenerative mental health disorders 2-times more likely affect activity-induced remodeling than report that while both development at fly NMJ require macroautophagy (hereafter referred autophagy), bifurcation autophagy pathway differentially impacts plasticity. demonstrate enhances activation but diminishes degradative autophagy, thereby driving towards autophagy-based secretion. Presynaptic knockdown Snap29, Sec22, or Rab8, proteins implicated secretory pathway, sufficient abolish remodeling. This study uncovers a transsynaptic signaling mechanism modulating

Language: Английский

Citations

15
Rho/Rok-dependent regulation of actomyosin contractility at tricellular junctions restricts epithelial permeability in Drosophila DOI Creative Commons
Thea Jacobs, Jone Isasti Sanchez,

Steven Reger

et al.

Current Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

1