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Investigating mechanisms of NPC1 proteostasis in human neurons
Organization UNIVERSITY OF MICHIGAN AT ANN ARBORLocation ANN ARBOR, UNITED STATESPosted 1 Jul 2024Deadline 31 Jan 2026 ⚠️
NIHUS FederalResearch GrantFY2025AddressAmino AcidsAssayAutophagocytosisBindingBioassayBiochemicalBiological AssayC-terminalCRISPR approachCRISPR based approachCRISPR interferenceCRISPR methodCRISPR methodologyCRISPR techniqueCRISPR technologyCRISPR toolsCRISPR-CAS-9CRISPR-based methodCRISPR-based techniqueCRISPR-based technologyCRISPR-based toolCRISPR-dCas9-mediated repressionCRISPR/CAS approachCRISPR/Cas methodCRISPR/Cas technologyCRISPR/Cas9CRISPR/Cas9 technologyCRISPR/dCas9 interferenceCRISPR/dCas9-mediated transcriptional inhibitionCRISPRiCas nuclease technologyCell BodyCell Surface GlycoproteinsCellsCessation of lifeChaperoneChildhoodCholesterolClustered Regularly Interspaced Short Palindromic Repeats approachClustered Regularly Interspaced Short Palindromic Repeats interferenceClustered Regularly Interspaced Short Palindromic Repeats methodClustered Regularly Interspaced Short Palindromic Repeats methodologyClustered Regularly Interspaced Short Palindromic Repeats techniqueClustered Regularly Interspaced Short Palindromic Repeats technologyCommunicationDataDeathDegenerative Neurologic DisordersDevelopmentDiseaseDisorderEndoplasmic ReticulumErgastoplasmFDA approvedFibroblastsGenesGeneticGoalsHalf-LifeHumanHydroxycholesterolsImageImpairmentIn vivo analysisInduced NeuronsInvestigationInvestigatorsIsoleucineL-ThreonineLearningLysosomal Enzyme DisordersLysosomal Storage DiseasesLysosomesMeasuresMediatingMembrane GlycoproteinsMichiganMissense MutationModern ManMolecular ChaperonesMolecular InteractionNPC1NPC1 geneNeimann-Pick's Disease Type CNerve CellsNerve UnitNervous System Degenerative DiseasesNeural CellNeural Degenerative DiseasesNeural Stem CellNeural degenerative DisordersNeurocyteNeurodegenerative DiseasesNeurodegenerative DisordersNeurologicNeurologic Degenerative ConditionsNeurologicalNeuronsNiemann Pick C DiseaseNiemann-Pick Type CNiemann-Pick's Disease Type COralPathway interactionsPatientsPhenotypePick Disease Type CPositionPositioning AttributePostdocPostdoctoral FellowProteinsPublishingResearchResearch AssociateResearch PersonnelResearch ResourcesResearchersResourcesRoleScientistSeizuresStable Isotope LabelingSterolsSurface GlycoproteinsTestingTherapeuticTherapeutic InterventionTherapeutic UsesThreonineTrainingUniversitiesWorkWritingaminoacidanalogautophagyautosomecholesterol analogclinical phenotypedegenerative diseases of motor and sensory neuronsdegenerative neurological diseasesdevelopmentalhiPSChuman iPShuman iPSChuman induced pluripotent cellhuman induced pluripotent stem cellshuman inducible pluripotent stem cellshuman inducible stem cellshuman progenitor cell derivedhuman stem cell-derivediNeuroniPSiPSCiPSCsimagingimprovedin vivo evaluationin vivo testinginborn lysosomal enzyme disorderinduced human pluripotent stem cellsinduced pluripotent cellinduced pluripotent stem cellinducible pluripotent cellinducible pluripotent stem cellintervention therapylate endosomeloss of function mutationlysosomal diseaselysosomal disorderlysosome storage diseasesmissense single nucleotide polymorphismmissense single nucleotide variantmissense variantnerve stem cellneural precursorneural precursor cellneural progenitorneural progenitor cellsneural stem and progenitor cellsneurodegenerative illnessneurogenic progenitorsneurogenic stem cellneuron developmentneuron progenitorsneuronalneuronal developmentneuronal progenitorneuronal progenitor cellsneuronal stem cellsneuroprogenitornovelpathwaypediatricpharmacologicpost-docpost-doctoralpost-doctoral traineeprogenitor and neural stem cellsprogressive neurodegenerationprotein homeostasisproteostasisrepressing CRISPR-dCas9 systemresearch associatesskillssocial rolesuccesstargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutically effectivetrafficking
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Abstract
Niemann-Pick disease type C is a childhood-onset, autosomal recessive, lysosomal storage disease
characterized by the accumulation of unesterified cholesterol. Clinical phenotypes are heterogeneous, but
typically include progressive neurodegeneration, seizures, and early death. Niemann-Pick C is commonly (~95%
of cases) caused by…
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