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TRIM9调控病毒诱导Ⅰ型干扰素表达的分子机制的开题报告.docx

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TRIM9调控病毒诱导Ⅰ型干扰素表达的分子机制的开题报告 Title:MolecularMechanismsofTRIM9inRegulatingVirus-InducedTypeIInterferonExpression Introduction: TypeIinterferon(IFN-I)playsacriticalroleininnateimmuneresponsestoviralinfections.Uponviralinfection,hostcellssensepathogen-associatedmolecularpatterns(PAMPs)throughpatternrecognitionreceptors(PRRs),leadingtotheactivationoftranscriptionfactors,suchasIRF3andNF-κB,whichdriveIFN-Iexpression.Severalcellularfactorshavebeenimplicatedinmodulatinginnateimmuneresponsestoviralinfections,includingthetripartitemotif-containing(TRIM)familyofproteins.Amongthem,TRIM9hasbeenshowntoplayanimportantroleinregulatingIFN-Iexpressioninresponsetoviralinfections.Inthisreport,wewilldiscussthemolecularmechanismsbywhichTRIM9regulatesvirus-inducedIFN-Iexpression. Significance: Theidentificationofcellularfactorsthatregulateinnateimmuneresponsestoviralinfectionsiscriticalforunderstandinghost-pathogeninteractionsanddevelopingeffectiveantiviraltherapeutics.TRIM9isanovelregulatorofinnateimmuneresponses,andunderstandingthemolecularmechanismsofitsactionwillprovidevaluableinsightsintohowthehostcombatsviralinfections. Objective: TheaimofthisstudyistoinvestigatethemolecularmechanismsunderlyingTRIM9-mediatedregulationofvirus-inducedIFN-Iexpression. Methods: Toachievethisobjective,wewilluseprimaryhumanandmousecells,includingmacrophagesandfibroblasts,toinvestigatetheroleofTRIM9inregulatingvirus-inducedIFN-Iexpression.WewilluseacombinationofgeneticandbiochemicalapproachestodeterminethemolecularmechanismsunderlyingTRIM9action,includingCRISPR-Cas9-mediatedknockout,RNAsequencing,ChIP-seq,co-immunoprecipitation,andprotein-proteininteractionassays. ExpectedResults: WeexpecttoshowthatTRIM9playsacriticalroleinregulatingvirus-inducedIFN-Iexpressionbymodulatingtheactivityofkeytranscriptionfactors,suchasIRF3andNF-κB.WealsoexpecttoidentifynovelTRIM9interactingpartnersthatcontributetoitsregulatoryfunctionsininnateimmunity. Conclusion: Inconclusion,thisstudyaimstoprovideacomprehensiveunderstandingo