grant
RNA associated mechanisms for antigen receptor gene diversification during immature B cell development
Organization COLUMBIA UNIVERSITY HEALTH SCIENCESLocation NEW YORK, UNITED STATESPosted 24 Jun 2024Deadline 30 Apr 2029
NIHUS FederalResearch GrantFY2025AICDAAICDA proteinAID geneAID proteinAbelson Murine Leukemia Viral Oncogene HomologAffinityAllelesAllelomorphsAntibodiesAntibody AffinityAntibody RepertoireAntigen ReceptorsAntigensAttenuatedAutomobile DrivingB blood cellsB cellB cellsB-Cell DeficiencyB-Cell DevelopmentB-CellsB-LymphocytesB-cellBiochemistryBiological ChemistryBiologyBlood Precursor CellBone MarrowBone Marrow Reticuloendothelial SystemCDA2 proteinCell FunctionCell LineCell PhysiologyCell ProcessCell TherapyCellLineCellular FunctionCellular PhysiologyCellular ProcessChromatinClass SwitchingClass SwitchingsCodeCoding SystemComplexCoupledDNADNA Damage RepairDNA Double Strand BreakDNA HelicasesDNA RearrangementDNA RecombinationDNA RepairDNA Single Strand BreakDNA Unwinding ProteinsDNA mutationDNA unwinding enzymeDataDefectDeoxyribonucleic AcidDiseaseDisorderDistalEnzyme GeneEnzymesEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessFunctional RNAGene ActivationGene ExpressionGene RearrangementGene TranscriptionGenerationsGenesGenetic ChangeGenetic RecombinationGenetic TranscriptionGenetic defectGenetic mutationGenomeGenome InstabilityGenomic InstabilityHeavy-Chain ImmunoglobulinsHematopoietic Progenitor CellsHematopoietic stem cellsHereditary DiseaseHumanHybridsIGHIGH@ gene clusterIg GenesIg Somatic HypermutationIgH locusImmune DiseasesImmune DisordersImmune DysfunctionImmune GlobulinsImmune System DiseasesImmune System DisorderImmune System DysfunctionImmune System and Related DisordersImmune systemImmunoglobulin Class SwitchingImmunoglobulin Class SwitchingsImmunoglobulin GenesImmunoglobulin Heavy Chain GenesImmunoglobulin Heavy GeneImmunoglobulin Heavy LocusImmunoglobulin Isotype-Switch RecombinationImmunoglobulin Somatic HypermutationImmunoglobulin Switch RecombinationImmunoglobulin V(D)J RearrangementImmunoglobulinsImmunologic DiseasesImmunological DiseasesImmunological DysfunctionImmunological System DysfunctionInborn Genetic DiseasesInherited disorderIsotype SwitchingIsotype SwitchingsKinasesLaboratoriesLifeLightLight-Chain ImmunoglobulinsLiquid substanceLoxP-flanked alleleMeasuresMediatingMiceMice MammalsMicroscopyModelingModern ManModificationMurineMusMutationNomenclatureNon-Polyadenylated RNANoncoding RNANontranslated RNAOncogene ABL1Oncogene SKIPathway interactionsPatientsPeptide Signal SequencesPhasePhosphotransferase GenePhosphotransferasesPhotoradiationPlayPost-Transcriptional ControlPost-Transcriptional RegulationPreventionProcessPropertyProteinsProtocolProtocols documentationRNARNA ExpressionRNA Gene ProductsRNA HelicaseRNA ProcessingRNA metabolismReceptor GeneRecombinationRegulationResearch DesignRibonucleic AcidRoleSETXSETX geneSKISKI geneSKI2SKI2WSKIV2LSKIV2L geneSecondary toSignal PeptideSignal SequencesSiteSpecificityStrains Cell LinesStudy TypeSubcellular ProcessSwitch RecombinationSystemTranscriptionTranscriptional ControlTranscriptional RegulationTransphosphorylasesTrichohepatoenteric syndromeUnscheduled DNA SynthesisUntranslated RNAV(D)J RearrangementV(D)J RecombinationVDJ rearrangementVDJ recombinationWorkabl Oncogeneactivation-induced cytidine deaminaseactivation-induced deaminaseadaptive immune responseantigen antibody affinityattenuateattenuatesbiochemical toolsbiochemistry toolsblood cell progenitorblood progenitorblood stem cellblood-forming stem cellcell based interventioncell mediated interventioncell mediated therapiescell-based therapeuticcell-based therapycellular therapeuticcellular therapycofactorcultured cell linedrivingenzyme activityepigeneticallyexosomeexperiencefloxedfloxed allelefluidgenome editinggenome mutationgenomic editinggenomic toolshelicasehematopoietic progenitorhematopoietic stem progenitor cellhemopoietic progenitorhemopoietic stem cellhereditary disorderheritable disorderhumoral immunity deficiencyhypoimmunityimmune deficiencyimmunodeficiencyimmunogenimmunoglobulin heavy chain locusimmunoglobulin light chain locusinborn errorinherited diseasesinherited genetic diseaseinherited genetic disorderinsightleukemia/lymphomaliquidlymphoma/leukemiamouse modelmurine modelmutantmutant mouse modelnoncodingpathwaypost-transcriptional gene regulationposttranscriptionalprotein signal sequencerepairrepairedsecondary lymph organsecondary lymphatic organsecondary lymphoid organsingle moleculesocial rolesomatic hypermutationstudy designtoolv ablv-SKI Avian Sarcoma Viral Oncogene Homologv-abl Genesv-abl Oncogenes
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PROJECT SUMMARY
Background: VDJ recombination, Class switch recombination (CSR) and somatic hypermutation (SHM) are
three B lymphocyte-specific processes that mediate antibody gene diversification. VDJ recombination requires
the DNA double-strand break generation by the recombination activation genes (RAG1 and RAG2) whereas
CSR and SHM require the…
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