grant

Single cell approaches to unravel transcriptional responses to drug pressure

Organization UNIVERSITY OF NOTRE DAMELocation NOTRE DAME, UNITED STATESPosted 1 Aug 2017Deadline 30 Apr 2029
NIHUS FederalResearch GrantFY2026AbscissionAfter CareAfter-TreatmentAftercareAnti-malarialsArtemisininsAssayBioassayBiological AssayBloodBlood Reticuloendothelial SystemCRISPR approachCRISPR based approachCRISPR methodCRISPR methodologyCRISPR techniqueCRISPR technologyCRISPR toolsCRISPR-CAS-9CRISPR-based methodCRISPR-based techniqueCRISPR-based technologyCRISPR-based toolCRISPR/CAS approachCRISPR/Cas methodCRISPR/Cas technologyCRISPR/Cas9CRISPR/Cas9 technologyCaloric RestrictionCandidate Disease GeneCandidate GeneCas nuclease technologyCell BodyCellsChlorochinChloroquineClustered Regularly Interspaced Short Palindromic Repeats approachClustered Regularly Interspaced Short Palindromic Repeats methodClustered Regularly Interspaced Short Palindromic Repeats methodologyClustered Regularly Interspaced Short Palindromic Repeats techniqueClustered Regularly Interspaced Short Palindromic Repeats technologyCuesDNA mutationDevelopmentDrug ExposureDrug TherapyDrug ToleranceDrug resistanceDrugsEffectivenessEnvironmentExcisionExperimental GeneticsExtirpationFeverFundingGene ExpressionGene TranscriptionGeneralized GrowthGenerationsGenesGeneticGenetic ChangeGenetic CrossesGenetic DeterminismGenetic EngineeringGenetic Engineering BiotechnologyGenetic Engineering Molecular BiologyGenetic PolymorphismGenetic TranscriptionGenetic defectGenetic mutationGenotypeGrantGrowthKhingaminLength of LifeLife CycleLife Cycle StagesLinkLongevityMalariaMapsMedicationMefloquineMolecularMutationP falciparumP. falciparumP.falciparumPaludismParasitesPatternPharmaceutical PreparationsPharmacological TreatmentPharmacotherapyPhenotypePlasmodium InfectionsPlasmodium falciparumPrediction of Response to TherapyPyrexiaQTLQuantitative Trait LociQuinineRNA ExpressionRecombinant DNA TechnologyRecombinantsRecoveryRemovalResearch ResourcesResistanceResourcesShapesSurgical RemovalTemperatureTimeTissue GrowthTranscriptionTransmissionTreatment FailureVariantVariationWorkanti-malarial agentsanti-malarial drugsarteannuinartemisinineasexualbenflumetolcalorie restrictioncandidate validationdevelopmentaldrug developmentdrug interventiondrug resistantdrug treatmentdrug/agentfebrilefebrisfitnessgenetic determinantgenetically engineeredgenome mutationglobal gene expressionglobal transcription profilelife courselumefantrinenext generationnovelontogenyparasite genomepharmaceutical interventionpharmacological interventionpharmacological therapypharmacology interventionpharmacology treatmentpharmacotherapeuticspolymorphismpost treatmentpredict therapeutic responsepredict therapy responsepressureprogramsqinghaosuquing hau sauquinghaosuresectionresistance mutationresistance to Drugresistantresistant mutationresistant to DrugresponsescRNA sequencingscRNA-seqsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingtherapy failuretherapy predictiontooltranscriptometransmission processtreatment predictiontreatment response predictiontreatment strategy
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SUMMARY
The transcriptional response to drug exposure shapes the ability for a parasite to survive and grow during and

after treatment. During the prior grant period, we developed multiple tools to identify the drivers of drug

resistance. Single cell RNAseq of Plasmodium falciparum genetic crosses now enables rapid, robust

estimation of single…

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