grant
Deciphering the structural basis of repeat-associated non-AUG (RAN) translation in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
Organization UNIVERSITY OF MICHIGAN AT ANN ARBORLocation ANN ARBOR, UNITED STATESPosted 18 Sept 2024Deadline 31 Aug 2029
NIHUS FederalResearch GrantFY20255' Untranslated Regions5'UTRAddressAffectAffinityAmyotrophic lateral sclerosis and frontotemporal degenerationAmyotrophic lateral sclerosis and frontotemporal dementiaAssayBacterial ToxinsBindingBioassayBiochemicalBiologic ModelsBiologicalBiological AssayBiological ModelsBiologyBrainBrain Nervous SystemC9ORF72Cell BodyCell IsolationCell SegregationCell SeparationCell Separation TechnologyCellsCodonCodon NucleotidesComplexCryo-electron MicroscopyCryoelectron MicroscopyDegenerative Neurologic DisordersDipeptidesDiseaseDisorderElectron CryomicroscopyEncephalonEndoribonucleasesEnvironmentEukaryotic Initiation FactorsEukaryotic Peptide Initiation FactorsEukaryotic Translation Initiation FactorsFTD/ALSFTLD/ALSFrontotemporal Lobar Degeneration/Amyotrophic lateral sclerosisGTP PhosphohydrolasesGTPasesGenerationsGenesGuanosine Triphosphate PhosphohydrolasesGuanosinetriphosphatasesHumanIn VitroIndividualInduced pluripotent stem cell derived neuronsInitiation CodonInitiation FactorsInitiator CodonIntervening SequencesIntronsInvestigatorsLocationMapsMass Photometry/Spectrum AnalysisMass SpectrometryMass SpectroscopyMass SpectrumMass Spectrum AnalysesMass Spectrum AnalysisMedicalMessenger RNAModel SystemModelingModern ManMolecularMolecular InteractionNerve CellsNerve DegenerationNerve UnitNervous System Degenerative DiseasesNervous System DiseasesNervous System DisorderNeural CellNeural Degenerative DiseasesNeural degenerative DisordersNeurocyteNeurodegenerative DiseasesNeurodegenerative DisordersNeurologic Degenerative ConditionsNeurologic DisordersNeurological DisordersNeuron DegenerationNeuron from iPSCNeuron from induced pluripotent stem cellsNeuronsNon-Polyadenylated RNANucleotidesPeptide Initiation FactorsProcessProteinsProteomicsRNARNA Gene ProductsRNA endonucleaseRegulationRegulatory ProteinResearchResearch PersonnelResearchersResolutionRibonucleic AcidRibosomesRoleScanningSiteStart CodonStructureSystemTransfectionTranslation InitiationTranslation Initiation FactorTranslational Initiation FactorTranslational RegulationTranslationsVisualizationWorkamyotrophic lateral sclerosis with frontotemporal dementiaamyotrophic lateral sclerosis/FTLDamyotrophic lateral sclerosis/frontotemporal dementiaamyotrophic lateral sclerosis/ftdbiologiccell sortingchromosome 9 open reading frame 72crosslinkcryo-EMcryoEMcryogenic electron microscopydegenerative diseases of motor and sensory neuronsdegenerative neurological diseaseseIF5Beukaryotic initiation factor-5Bfrontotemporal dementia-amyotrophic lateral sclerosisfrontotemporal lobar dementia amyotrophic lateral sclerosisgenetic approachgenetic regulatory proteingenetic strategyguanosinetriphosphataseiPS neuronsiPSC derived-neuronsinduced pluripotent stem cell neuronsinnovateinnovationinnovativeinsightinsoluble aggregatemRNAmRNA Leader SequencesmRNA Translationmutantneural degenerationneurodegenerationneurodegenerativeneurodegenerative illnessneurological degenerationneurological diseaseneuronalneuronal degenerationneurons derived from induced pluripotent stem cellsneurons differentiated from induced pluripotent stem cellsnew drug targetnew druggable targetnew pharmacotherapy targetnew therapeutic targetnew therapy targetnovelnovel drug targetnovel druggable targetnovel pharmacotherapy targetnovel therapeutic targetnovel therapy targetpeptide initiation factor eIF-5Bprotein aggregateprotein aggregationreconstitutereconstitutionrecruitregulatory gene productresolutionssocial roletooltranslationtranslation factor
Description preview
Expansion of a hexanucleotide GGGGCC repeat within the first intron of the C9orf72 gene is the
primary monogenic cause for both Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal
Dementia (FTD). Despite its intronic location, expanded GGGGCC repeat is retained in the
mature mRNA, supporting a non-canonical translation initiation mechanism…
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