grant
Poison exons in epilepsy and neurodevelopment
Organization NORTHWESTERN UNIVERSITYLocation CHICAGO, UNITED STATESPosted 1 Jun 2024Deadline 31 May 2029
NIHUS FederalResearch GrantFY2025ASO therapeuticsASO therapyASO treatmentAddressAlternate SplicingAlternative RNA SplicingAlternative SplicingAnti-sense RNAAntibodiesAntisense AgentAntisense Oligonucleotide TherapyAntisense OligonucleotidesAtlasesBody TissuesBrainBrain Nervous SystemCell BodyCellsCerebrumCharacteristicsChildhoodCicloheximideClinical TrialsCodonCodon NucleotidesCommunitiesCortical MalformationCycloheximideDataData SetDegenerative Neurologic DisordersDevelopmentDiseaseDisorderDorsalElementsEncephalonEpilepsyEpileptic SeizuresEpilepticsExonsFutureGene variantGenesGeneticGenetic PredispositionGenetic Predisposition to DiseaseGenetic SusceptibilityGenetic propensityGenomeGenomicsHumanImmune PrecipitationImmunoblottingImmunoprecipitationIndividualInduced pluripotent stem cell derived neuronsInherited PredispositionInherited SusceptibilityIsoformsKnowledgeLeadMapsMass Photometry/Spectrum AnalysisMass SpectrometryMass SpectroscopyMass SpectrumMass Spectrum AnalysesMass Spectrum AnalysisMiceMice MammalsModern ManMurineMusNa(v)1.1Nav1.1Nervous System Degenerative DiseasesNervous System DiseasesNervous System DisorderNeural Degenerative DiseasesNeural DevelopmentNeural degenerative DisordersNeurodegenerative DiseasesNeurodegenerative DisordersNeurodevelopmental DisorderNeurologicNeurologic Degenerative ConditionsNeurologic DisordersNeurologicalNeurological Development DisorderNeurological DisordersNeuron from iPSCNeuron from induced pluripotent stem cellsNon-Polyadenylated RNANon-sense Mediated DecayNonsense-Mediated DecayOrganoidsOutcome StudyPathogenicityPatient-specific stem cellsPatientsPb elementPoisonProcessPropertyProtein IsoformsProteinsProteomicsRNARNA Gene ProductsRNA SeqRNA SplicingRNA sequencingRNA targeting drugRNA targeting therapeuticsRNA-Binding ProteinsRNA-targeting therapyRNAseqRegulationReporterResearchRibonucleic AcidRoleSCN1A proteinSeizure DisorderSingle cell seqSpecificitySpliceosomesSplicingTechnologyTimeTissuesToxic ChemicalToxic SubstanceTranscriptValidationVariantVariationWestern BlottingWestern Immunoblottingacquired epilepsyallelic variantanti-sense oligonucleotide druganti-sense oligonucleotide therapyanti-sense oligonucleotide treatmentanti-sense therapyantisense drugantisense oligoantisense oligonucleotide therapeuticantisense therapeuticsantisense therapybrain tissuecandidate identificationcell typecerebralcombinatorialdata integrationdegenerative diseases of motor and sensory neuronsdegenerative neurological diseasesdevelopmentalepilepsiaepileptogenicfetalgenetic etiologygenetic mechanism of diseasegenetic variantgenetic vulnerabilitygenetically predisposedgenome sequencinggenomic variantglobal gene expressionglobal transcription profileheavy metal Pbheavy metal leadhuman fetal brainiPSiPS neuronsiPSCiPSC derived-neuronsiPSCsinduced pluripotent cellinduced pluripotent stem cellinduced pluripotent stem cell neuronsinducible pluripotent cellinducible pluripotent stem cellinsightinterestknock-downknockdownlong read seqlong-read sequencinglong-read transcript sequencinglow-frequency mutationmachine learning based methodmachine learning methodmachine learning methodologiesmultidisciplinaryneurodegenerative illnessneurodevelopmentneurodevelopmental diseaseneurological diseaseneurons derived from induced pluripotent stem cellsneurons differentiated from induced pluripotent stem cellsnoveloverexpressoverexpressionpatient progenitor cellpatient stem cellpediatricpoison controlprematureprematuritypreventpreventingprogenitor cell modelprogenitor modelprotein blottingrare allelerare mutationrare variantsingle cell next generation sequencingsingle cell sequencingsocial rolestem and progenitor cell modelstem cell based modelstem cell derived modelstem cell modelstem cell organoidsstem cell-derived organoidstoxic compoundtranscriptometranscriptome sequencingtranscriptomic sequencingvalidationsweb toolweb-based tool
Description preview
Project summary
Exons in the genome that lead to the introduction of premature truncation (stop) codon and mark these
transcripts as targets for nonsense-mediated decay are called poison exons (PEs). These PEs are alternatively
spliced throughout mouse and human neurodevelopment and function. Moreover, genetic variants that perturb
the splicing of…
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