Genetic Analysis of Resistance to Viral Infection
抗病毒感染的遗传分析
基本信息
- 批准号:9087128
- 负责人:
- 金额:$ 262.77万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-08-15 至 2017-06-30
- 项目状态:已结题
- 来源:
- 关键词:Adaptor Protein Complex 3Adaptor Signaling ProteinAddressAffectAgeAllelesAntiviral AgentsAntiviral ResponseAreaAutophagocytosisBiochemicalBunyavirus InfectionsCRSP3 geneCategoriesCell physiologyCellsCellular StressCessation of lifeChildCommunicationCommunitiesCompetenceComplexComputer SimulationCryopreservationCytomegalovirusCytomegalovirus InfectionsDNADendritic CellsDerivation procedureDrosophila genusElementsEmbryoEndosomesExtended FamilyFibroblastsFundingGene ExpressionGene TargetingGenerationsGenesGeneticGenetic MaterialsGenetic TechniquesGenomic DNAGoalsGrantGray unit of radiation doseHIVHealthHerpesviridae InfectionsHomologous GeneHost DefenseHost resistanceHumanI-kappa B ProteinsImageImmuneImmune responseImmune systemIndividualInfectionInsectaInstitutesInterferon Type IInterferonsInvestigationKnock-outKnockout MiceLearningLifeLipopolysaccharidesMammalian CellMammalsMapsMassive Parallel SequencingMeasuresMediatingMedical centerMedicineMembrane Protein TrafficMemoryMethodsMicrobeModelingMolecularMovementMurid herpesvirus 1MusMutagenesisMutationNatural ImmunityNatural Killer CellsNatural regenerationNucleic AcidsOrganismParticipantPathway interactionsPharmaceutical PreparationsPhysiologyPluripotent Stem CellsPopulationPost-Transcriptional RegulationPost-Translational Protein ProcessingPredispositionPrincipal InvestigatorProcessProductivityProliferatingProteinsRNARNA InterferenceReactionReagentRecording of previous eventsRegulationResearchResistanceResistance to infectionResolutionRift Valley fever virusRiskRoleSignal PathwaySignal TransductionSmall RNASmallpoxSpeedSting InjuryStructural ModelsSystemic Lupus ErythematosusTLR7 geneTalentsTechnologyTherapeuticTimeToll-like receptorsTranscriptional RegulationTransmembrane TransportUniversitiesUrsidae FamilyVaccinesViralViral GenesViral PathogenesisVirusVirus DiseasesWorkWritingZinc Fingersantiviral immunitybasecombatcopingdeep sequencingdesignexpression cloningflyforward geneticsgene inductiongene interactiongenetic analysisgenome sequencinghuman diseasehuman mortalityinduced pluripotent stem cellmembermolecular targeted therapiesmutantmutation screeningnew technologypathogenpressurepreventprogramsreceptorresistance generesistance mechanismresponsereverse geneticsscreeningsensorsimulationsmall moleculesoundstem cell technologytranscription factorviral DNAviral RNAwhole genome
项目摘要
DESCRIPTION (provided by applicant): The present application extends a successful multifaceted investigation of host resistance to viral infection. The strengths of our approach include: 1) an unbiased component based on mutagenesis combined with a hypothesis-driven component; 2) the study of distantly related organisms (mice and Drosophila) to appreciate which elements of defense are conserved; 3) the embrace of new and powerful methods to support our efforts. In our work to date, we have collectively identified new sensors (e.g., LGP2; DICER-2) necessary for activation of antiviral defenses, and delineated pathways of response to viruses, both at a biochemical level and in terms of communication between cells. We have identified previously unknown molecular participants
in host defense. Among these are channel proteins (SLC15A4; KCNJ8/SUR2), transcription factors (IKB;AKIRIN2), proteins concerned with membrane trafficking or organellar mobility (AP3B1; STING; TR1M56; ATG9A; UNC93B), cell stress (SLFN2), post-translational modification (TRIM56; TR1M23), and endosome physiology (SLC15A4). Some of these proteins are members of extended families and may open the way to broad new models of host defense. Others highlight the importance of intermediary steps in host defense (e.g., the movement of molecules within cells) in a way that has not been considered before. Each participating group (Dallas, Osaka, and Strasbourg) has its special talents, and these have been combined to take us beyond genetics per se, incorporating new technologies that will accelerate the discovery of essential elements of the host defense apparatus. We recognize that it is not enough to possess a list of parts to understand how a machine operates. As new proteins are shown to be essential for particular aspects of host defense, we will establish how they interact with one another and/or other proteins to support resistance; how they catalyze particular reactions within cells, and how they drive or suppress the expression of genes in what we see as a highly dynamic process. We view the continuation of this POl as an opportunity to build upon an approach with established productivity: one that has generated new molecules, concepts, and reagents for use by the scientific community as a whole. The POl has been, and will continue to be, highly collaborative in the exchange of methods, genetic materials, and most importantly, ideas, ultimately derived from genetics.
描述(由申请人提供):本申请扩展了对宿主对病毒感染的抵抗力的成功的多方面研究。我们方法的优势包括:1)基于诱变的无偏成分与假设驱动成分相结合; 2)研究远缘生物(小鼠和果蝇)以了解哪些防御要素是保守的; 3)采用新的、强大的方法来支持我们的努力。在迄今为止的工作中,我们已经共同确定了激活抗病毒防御所需的新传感器(例如 LGP2;DICER-2),并在生化水平和细胞间通信方面描绘了对病毒的反应途径。我们已经确定了以前未知的分子参与者
在主机防御中。 其中包括通道蛋白(SLC15A4;KCNJ8/SUR2)、转录因子(IKB;AKIRIN2)、与膜运输或细胞器迁移有关的蛋白(AP3B1;STING;TR1M56;ATG9A;UNC93B)、细胞应激(SLFN2)、翻译后修饰(TRIM56;TR1M23)和内体 生理学(SLC15A4)。其中一些蛋白质是大家族的成员,可能为广泛的宿主防御新模型开辟道路。其他人以一种以前从未考虑过的方式强调了宿主防御中中间步骤(例如细胞内分子的运动)的重要性。每个参与小组(达拉斯、大阪和斯特拉斯堡)都有其特殊才能,这些才能使我们超越遗传学本身,融入新技术,加速发现宿主防御装置的基本要素。我们认识到,仅仅拥有一份零件清单不足以了解机器的运行方式。由于新的蛋白质被证明对于宿主防御的特定方面至关重要,我们将确定它们如何与彼此和/或其他蛋白质相互作用以支持抵抗力;它们如何催化细胞内的特定反应,以及它们如何在我们所认为的高度动态的过程中驱动或抑制基因的表达。我们认为这一 POl 的延续是一个机会,可以建立一种具有既定生产力的方法:一种产生新分子、概念和试剂供整个科学界使用的方法。 POl 一直并将继续在方法、遗传材料以及最重要的、最终源自遗传学的思想的交流方面保持高度协作。
项目成果
期刊论文数量(67)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Sensing viral RNAs by Dicer/RIG-I like ATPases across species.
- DOI:10.1016/j.coi.2015.01.009
- 发表时间:2015-02
- 期刊:
- 影响因子:7
- 作者:Paro S;Imler JL;Meignin C
- 通讯作者:Meignin C
TANK is a negative regulator of Toll-like receptor signaling and is critical for the prevention of autoimmune nephritis.
- DOI:10.1038/ni.1771
- 发表时间:2009-09
- 期刊:
- 影响因子:30.5
- 作者:
- 通讯作者:
Verloren negatively regulates the expression of IMD pathway dependent antimicrobial peptides in Drosophila.
- DOI:10.1038/s41598-021-94973-0
- 发表时间:2021-07-30
- 期刊:
- 影响因子:4.6
- 作者:Prakash P;Roychowdhury-Sinha A;Goto A
- 通讯作者:Goto A
Special delivery: granulin brings CpG DNA to Toll-like receptor 9.
特别递送:颗粒蛋白将 CpG DNA 带到 Toll 样受体 9。
- DOI:10.1016/j.immuni.2011.04.001
- 发表时间:2011
- 期刊:
- 影响因子:32.4
- 作者:Moresco,EvaMarieY;Beutler,Bruce
- 通讯作者:Beutler,Bruce
Crystal structure of Diedel, a marker of the immune response of Drosophila melanogaster.
- DOI:10.1371/journal.pone.0033416
- 发表时间:2012
- 期刊:
- 影响因子:3.7
- 作者:Coste F;Kemp C;Bobezeau V;Hetru C;Kellenberger C;Imler JL;Roussel A
- 通讯作者:Roussel A
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BRUCE A BEUTLER其他文献
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{{ truncateString('BRUCE A BEUTLER', 18)}}的其他基金
Modulation of NOD Strain Diabetes by ENU-Induced Mutations
ENU 诱导突变对 NOD 菌株糖尿病的调节
- 批准号:
10642549 - 财政年份:2023
- 资助金额:
$ 262.77万 - 项目类别:
Core B - Sequencing, Genotyping and Automated Mapping
核心 B - 测序、基因分型和自动作图
- 批准号:
10642551 - 财政年份:2023
- 资助金额:
$ 262.77万 - 项目类别:
Project 2 - Verification and Molecular Mechanisms of T1D Modifier Mutations
项目2-T1D修饰突变的验证和分子机制
- 批准号:
10642554 - 财政年份:2023
- 资助金额:
$ 262.77万 - 项目类别:
Automated Forward Genetic Analysis of Adaptive Immunity
适应性免疫的自动正向遗传分析
- 批准号:
9158963 - 财政年份:2016
- 资助金额:
$ 262.77万 - 项目类别:
Automated Forward Genetic Analysis of Adaptive Immunity
适应性免疫的自动正向遗传分析
- 批准号:
10623164 - 财政年份:2016
- 资助金额:
$ 262.77万 - 项目类别:
Automated Forward Genetic Analysis of Adaptive Immunity
适应性免疫的自动正向遗传分析
- 批准号:
10209864 - 财政年份:2016
- 资助金额:
$ 262.77万 - 项目类别:
Automated Forward Genetic Analysis of Adaptive Immunity
适应性免疫的自动正向遗传分析
- 批准号:
10328571 - 财政年份:2016
- 资助金额:
$ 262.77万 - 项目类别: