Mechanism of a Male Killing Toxin in a Drosophila endosymbiont
果蝇内共生体中雄性致死毒素的机制
基本信息
- 批准号:10432565
- 负责人:
- 金额:$ 23.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-04-15 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAllelesAmino AcidsAnimalsAnkyrin RepeatAnkyrinsApoptosisArthropodsBacterial ProteinsBacterial ToxinsBindingBinding ProteinsBiologicalBiological AssayBiological ModelsBiologyCandidate Disease GeneCellsCellular biologyChromatin StructureCo-ImmunoprecipitationsComplexCoupledDataDevelopmentDosage Compensation (Genetics)Drosophila genusDrosophila melanogasterEmbryoEmbryonic DevelopmentEnvironmentEukaryotic CellEventEvolutionExhibitsFemaleGenesGeneticGenetic CrossesGenetic PolymorphismGenetic ScreeningHumanHybridsImmunityInfectionLengthLibrariesLinkMass Spectrum AnalysisMediatingMolecularMolecular BiologyMutationN-terminalNatural ResistanceOpen Reading FramesOvaryParasitesPathway interactionsPhenotypePlanet EarthPopulationPost-Translational Protein ProcessingProteinsResistanceScaffolding ProteinShapesSingle Nucleotide PolymorphismSpiroplasmaStretchingStructureTestingTissuesToxic effectToxicity TestsToxinVariantVirulenceWorkYeastsarms racebaseendosymbiontexperimental studyflygenetic variantgenome wide association studyin vivoknock-downmalemimicrynoveloffspringovarian neoplasmpathogenprotein functionprotein protein interactionsex determinationsymbionttool
项目摘要
PROJECT SUMMARY/ABSTRACT
The co-evolution of bacterial protein toxins and their targets has led to the discovery of many novel protein
modifications and the development of applications in molecular biology. Arthropods, the most diverse phylum
on Earth, are hosts to many bacterial symbionts that secrete diverse toxins of unknown function during
infection. The maternally transmitted, intracellular parasite Spiroplasma poulsonii encodes one such toxin
(Spiroplasma androcidin or Spaid) that causes male killing in its natural host Drosophila melanogaster. This
proposed project aims to understand how the bacterial toxin Spaid recognizes the host cellular environment to
specifically kill males. To that end, we use the Spiroplasma-Drosophila model system and a combination of
genetics and molecular biology to identify specific host proteins targeted by Spaid and how the toxin binds
these proteins.
Previous work has suggested that Spiroplasma, via Spaid, detects the presence of the male specific lethal
complex in flies. This complex is responsible for dosage compensation in male flies, which lack a second copy
of the X. It is formed during early development in males and is part of the Drosophila sex determination
pathway. Given this result, we hypothesized that natural resistance to Spaid would exist in Drosophila
populations, that the target of Spaid is part of the dosage compensation complex (dcc), and that Spaid directly
binds to dcc components, altering their activity. Our strong preliminary data suggest that we are correct, as we
find natural variants of Drosophila melanogaster (within the DGRP), which produce males in the presence of
Spaid and/or Spiroplasma. We also find that tissue specific knockdown of dcc components partially suppresses
Spaid toxicity in male tissue.
Towards this hypothesis, and guided by strong preliminary data, we propose to pursue two Specific Aims to
identify host proteins that interact directly with the Spaid toxin and characterize how variation within host
proteins and Spaid affect male killing at the molecular and cellular level. We will (1) Identify Spaid targets using
a yeast 2-hybrid screen and co-immunoprecipitation, (2) identify suppressors of Spaid toxicity using natural
variation in Drosophila and a genetic screen.
Results from these experiments will illustrate how a bacterial toxin manipulates the host cellular environment.
项目总结/文摘
项目成果
期刊论文数量(0)
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Irene Newton其他文献
Irene Newton的其他文献
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{{ truncateString('Irene Newton', 18)}}的其他基金
Mechanism of a Male Killing Toxin in a Drosophila endosymbiont
果蝇内共生体中雄性致死毒素的机制
- 批准号:
10609906 - 财政年份:2022
- 资助金额:
$ 23.78万 - 项目类别:
Identifying Wolbachia effectors that facilitate host infection
识别促进宿主感染的沃尔巴克氏体效应子
- 批准号:
10132974 - 财政年份:2019
- 资助金额:
$ 23.78万 - 项目类别:
Identifying Wolbachia effectors that facilitate host infection
识别促进宿主感染的沃尔巴克氏体效应子
- 批准号:
10378723 - 财政年份:2019
- 资助金额:
$ 23.78万 - 项目类别:
Identifying Wolbachia effectors that facilitate host infection
识别促进宿主感染的沃尔巴克氏体效应子
- 批准号:
10613456 - 财政年份:2019
- 资助金额:
$ 23.78万 - 项目类别:
Determining the mechanism of Wolbachia pathogen blocking
确定沃尔巴克氏体病原体阻断机制
- 批准号:
9242754 - 财政年份:2016
- 资助金额:
$ 23.78万 - 项目类别:
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