grant
Multiplexed Locus-Specific Hypermutation for Functional Characterization of the Coding and Noncoding Genome
Organization BROAD INSTITUTE, INC.Location CAMBRIDGE, UNITED STATESPosted 8 Jan 2025Deadline 31 Dec 2028
NIHUS FederalResearch GrantFY2025Alkylating AgentsAlkylatorsArchitectureBacteriaCRISPRCRISPR/Cas systemCell Communication and SignalingCell LineCell SignalingCellLineChromatinClustered Regularly Interspaced Short Palindromic RepeatsCodeCoding SystemComplexComputing MethodologiesDNA HelicasesDNA Nicking EnzymeDNA Unwinding ProteinsDNA mutationDNA unwinding enzymeDeaminaseDevelopmentDirected Molecular EvolutionDiseaseDisorderDrug resistanceElementsEndonuclease IEngineeringEngineering / ArchitectureEnhancer ElementsEvaluationEvolutionExtracellular Signal-Regulated Kinase GeneFunctional RNAGene Action RegulationGene ExpressionGene Expression RegulationGene RegulationGene Regulation ProcessGenerationsGenesGeneticGenetic ChangeGenetic DiversityGenetic Enhancer ElementGenetic VariationGenetic defectGenetic mutationGenetics-MutagenesisGenomeGenomic SegmentGenomicsHumanHuman GenomeIntracellular Communication and SignalingLaboratoriesLinkMAP Kinase GeneMAP Kinase Kinase 1MAP2K1MAP2K1 geneMAPKMAPK/ERK Kinase 1MAPKK1MEK-1MEK1MEKsMKK1MethodsMitogen-Activated Protein Kinase GeneMitogen-Activated Protein Kinase Kinase-1ModalityModern ManMutagenesisMutagenesis Molecular BiologyMutationNatural SelectionsNickaseNoncoding RNANontranslated RNAPRKMK1Pathway interactionsPopulationPopulation StudyProcessProtein EngineeringRegulatory ElementResistanceResolutionRoleSignal PathwaySignal TransductionSignal Transduction SystemsSignalingSignaling Factor Proto-OncogeneSignaling Pathway GeneSignaling ProteinSingle Base PolymorphismSingle Nucleotide PolymorphismSpecificityStrains Cell LinesTechnologyTestingUntranslated RNAVariantVariationWorkbasebase editorbasesbiological signal transductionbiological systemscancer drug resistancechemotherapycomputational methodologycomputational methodscomputer based methodcomputer methodscomputing methodcultured cell linedesigndesigningdevelopmentaldirected evolutiondrug resistantenhancer sequencegene editing platformgene editing systemgene editing technologygene editing toolsgene functiongene regulatory networkgene-editing toolkitgenetic enhancer sequencegenetic protein engineeringgenome mutationgenome scalegenome segmentgenome-widegenomewidegenomic regionhelicasehuman whole genomeimprovedinhibitorinterestmammalian genomemutantnew drug treatmentsnew drugsnew pharmacological therapeuticnew therapeuticsnew therapynext generationnext generation therapeuticsnoncodingnovelnovel drug treatmentsnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel therapeuticsnovel therapypathwaypopulation-based studypopulation-level studyprotein designprototyperate of changeresistance mechanismresistance mutationresistance to Drugresistance to cancer drugsresistantresistant mechanismresistant mutationresistant to Drugresistant to cancer drugsresolutionsscreeningscreeningssingle nucleotide variantsmall moleculesocial rolestudies of populationsstudy of the populationtool
Description preview
SUMMARY
While laboratory directed evolution has become a workhorse for generating novel
therapeutics and synthetic biomolecules, few tools exist for directly evolving the endogenous
mammalian genome. Most tools have extremely broad or narrow targeting windows (e.g.,
alkylators that introduce mutations genome-wide2 or CRISPR base-editors that…
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