grant
Leveraging large-scale genomics to dissect A-to-I editing in brain aging and Alzheimer's disease
Organization ICAHN SCHOOL OF MEDICINE AT MOUNT SINAILocation NEW YORK, UNITED STATESPosted 1 May 2024Deadline 31 Jan 2029
NIHUS FederalResearch GrantFY2025AD dementiaAD related dementiaADAR1ADAR2ADARB1 proteinADRDAddressAdenosineAffinityAgingAlternate SplicingAlternative RNA SplicingAlternative SplicingAlzheimer Type DementiaAlzheimer disease dementiaAlzheimer sclerosisAlzheimer syndromeAlzheimer'sAlzheimer's DiseaseAlzheimer's and related dementiasAlzheimer's dementia and related dementiaAlzheimer's dementia or related dementiaAlzheimer's disease and related dementiaAlzheimer's disease and related disordersAlzheimer's disease or a related dementiaAlzheimer's disease or a related disorderAlzheimer's disease or related dementiaAlzheimer's disease related dementiaAlzheimers DementiaAmentiaAmino Acid SequenceBindingBiologicalBrainBrain Nervous SystemCNS Nervous SystemCausalityCell modelCellular modelCentral Nervous SystemDRADA2b proteinDataDeaminationDegenerative Neurologic DisordersDementiaDevelopmentDiathesisDiseaseDisease susceptibilityDisorderDouble-Stranded RNAEncephalonEnzyme GeneEnzymesEtiologyEventGWA studyGWASGene ExpressionGeneticGenetic DiseasesGenetic DiversityGenetic RiskGenetic VariationGenomeGenomicsGenotypeGliaGlial CellsGuanosineHumanImmune Cell ActivationIndividualInosineIsoformsKnowledgeKolliker's reticulumLinkMapsMethodsMicroRNAsModern ManModificationMolecularMolecular InteractionNerve CellsNerve UnitNervous System Degenerative DiseasesNeural CellNeural Degenerative DiseasesNeural degenerative DisordersNeuraxisNeurocyteNeurodegenerative DiseasesNeurodegenerative DisordersNeurogliaNeuroglial CellsNeurologic Degenerative ConditionsNeuronsNon-Polyadenylated RNANon-neuronal cellNonneuronal cellORFsOpen Reading FramesOutcomePathogenesisPathologyPlayPrimary Protein StructurePrimary Senile Degenerative DementiaProcessProtein Coding RegionProtein IsoformsQTLQuantitative Trait LociRNARNA EditingRNA Gene ProductsRNA SplicingRNA, Messenger, EditingRegional AnatomyRegulationResearchRibonucleic AcidRisk-associated variantRoleSamplingSeveritiesSiteSplicingStructureTherapeutic InterventionTranscriptTranscriptional ControlTranscriptional RegulationTranslational RegulationTranslationsValidationWorkaberrant agingabnormal agingadenosine deaminase that acts on RNAaged brainaging brainbasebasesbiologicbrain cellcausationcell typecohortdADARdegenerative diseases of motor and sensory neuronsdegenerative neurological diseasesdementia riskdevelopmentaldisease causationdisease riskdisorder riskdouble-stranded RNA-specific adenosine deaminasedsRNAdsRNA adenosine deaminasedsRNA-specific adenosine deaminasedysfunctional age related changedysfunctional aginggene functiongene locusgenetic conditiongenetic disordergenetic informationgenetic locusgenome scalegenome wide associationgenome wide association scangenome wide association studygenome-widegenomewidegenomewide association scangenomewide association studygenomic locationgenomic locusglobal gene expressionglobal transcription profilehiPSChuman iPShuman iPSChuman induced pluripotent cellhuman induced pluripotent stem cellshuman inducible pluripotent stem cellshuman inducible stem cellsimmune activationimpaired aginginduced human pluripotent stem cellsinnovateinnovationinnovativeinsightintervention therapyliability to diseaselife spanlifespanmaladaptive agingmiRNAnatural agingnerve cementneurodegenerative illnessneuronalneuropathologicneuropathologicalneuropathologynew drug targetnew druggable targetnew pharmacotherapy targetnew therapeutic targetnew therapy targetnormal agingnormative agingnovel drug targetnovel druggable targetnovel pharmacotherapy targetnovel therapeutic targetnovel therapy targetpathological age related changespathological agingposttranscriptionalprimary degenerative dementiaprotein sequencerisk allelerisk factor for dementiarisk for dementiarisk generisk genotyperisk locirisk locusrisk variantsenile dementia of the Alzheimer typesocial rolespatial and temporalspatial temporalspatiotemporaltargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic targettherapeutically effectivetooltranscriptometranscriptomicstranslationvalidationswhole genome association analysiswhole genome association study
Description preview
PROJECT SUMMARY
Post-transcriptional modifications through adenosine-to-inosine (A-to-I) editing are critical for maintaining the
diverse repertoire of RNA transcripts in the human brain. These modifications occur at isolated adenosines and
across multiple consecutive adenosines within an extended region along the same RNA molecule. A-to-I editing…
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