2024
Enhanced eMAGE applied to identify genetic factors of nuclear hormone receptor dysfunction via combinatorial gene editing
Ciaccia P, Liang Z, Schweitzer A, Metzner E, Isaacs F. Enhanced eMAGE applied to identify genetic factors of nuclear hormone receptor dysfunction via combinatorial gene editing. Nature Communications 2024, 15: 5218. PMID: 38890276, PMCID: PMC11189492, DOI: 10.1038/s41467-024-49365-z.Peer-Reviewed Original ResearchConceptsGenome modificationEngineered nucleasesMultiplex genome engineeringEfficient multiplex editingLigand-binding domain of human estrogen receptor alphaMethods of genome editingCancer-associated mutationsHomology-directed repairMismatch repair systemLigand-binding domainSaccharomyces cerevisiaeYeast modelSynthetic genomesGenome engineeringPolygenic basisComplex phenotypesBackground mutationsGenomeGenome editingMultiplex editingEditing frequencyHuman estrogen receptor alphaDNA breaksEstrogen receptor alphaMMR inactivation
2023
Metagenomics harvested genus-specific single-stranded DNA-annealing proteins improve and expand recombineering in Pseudomonas species
Asin-Garcia E, Garcia-Morales L, Bartholet T, Liang Z, Isaacs F, dos Santos V. Metagenomics harvested genus-specific single-stranded DNA-annealing proteins improve and expand recombineering in Pseudomonas species. Nucleic Acids Research 2023, 51: 12522-12536. PMID: 37941137, PMCID: PMC10711431, DOI: 10.1093/nar/gkad1024.Peer-Reviewed Original ResearchConceptsPseudomonas genusMetabolic engineering effortsSynthetic biology applicationsGenetic engineering toolsGenome editing capabilitiesRelated speciesStress resistanceValuable hostBiology applicationsActive variantsEnvironmental biotechnologyDifferent PseudomonasRecombineeringPseudomonas speciesPseudomonas putidaPseudomonas fluorescensSpeciesGenusNGS analysisCharacteristics of toleranceRemarkable abilityProteinEngineering effortsPseudomonasValuable compounds
2011
Precise Manipulation of Chromosomes in Vivo Enables Genome-Wide Codon Replacement
Isaacs FJ, Carr PA, Wang HH, Lajoie MJ, Sterling B, Kraal L, Tolonen AC, Gianoulis TA, Goodman DB, Reppas NB, Emig CJ, Bang D, Hwang SJ, Jewett MC, Jacobson JM, Church GM. Precise Manipulation of Chromosomes in Vivo Enables Genome-Wide Codon Replacement. Science 2011, 333: 348-353. PMID: 21764749, PMCID: PMC5472332, DOI: 10.1126/science.1205822.Peer-Reviewed Original ResearchConceptsGenome engineeringSynonymous codon substitutionsGenome engineering technologiesSynthetic lethal effectMegabase scaleCodon replacementsTAA codonCodon substitutionsRecombination frequencyCodon modificationGenetic landscapeEscherichia coliGenomeChromosomesCodonPrecise changesLethal effectsPrecise manipulationEngineering technologyNucleotidesColiPhenotypeTagsModification
2009
Programming cells by multiplex genome engineering and accelerated evolution
Wang HH, Isaacs FJ, Carr PA, Sun ZZ, Xu G, Forest CR, Church GM. Programming cells by multiplex genome engineering and accelerated evolution. Nature 2009, 460: 894-898. PMID: 19633652, PMCID: PMC4590770, DOI: 10.1038/nature08187.Peer-Reviewed Original Research
2006
RNA synthetic biology
Isaacs FJ, Dwyer DJ, Collins JJ. RNA synthetic biology. Nature Biotechnology 2006, 24: 545-554. PMID: 16680139, DOI: 10.1038/nbt1208.Peer-Reviewed Original ResearchConceptsRNA moleculesSynthetic biologyDiverse regulatory rolesRNA synthetic biologyNew biological functionsCellular control systemsSensors of intracellularMammalian systemsRNA componentBiological functionsGene expressionNatural versatilityCellular behaviorRegulatory roleRNA systemsEnvironmental stimuliBiological networksSmall moleculesBiologyNucleic acidsMoleculesYeastProteinBacteriaIntracellular
2004
Engineered riboregulators enable post-transcriptional control of gene expression
Isaacs FJ, Dwyer DJ, Ding C, Pervouchine DD, Cantor CR, Collins JJ. Engineered riboregulators enable post-transcriptional control of gene expression. Nature Biotechnology 2004, 22: 841-847. PMID: 15208640, DOI: 10.1038/nbt986.Peer-Reviewed Original ResearchConceptsStem-loop structureGene expressionPost-transcriptional controlPost-transcriptional regulation systemSmall noncoding RNAsTrans targetsCis-repressive sequenceRibosome bindingNoncoding RNAsEndogenous RNATarget genesCis sequencesRegulatory roleEscherichia coliRNABiological networksRiboregulatorsMechanistic actionGenesExpressionRecent studiesSequenceRegulation systemTranscriptionPromoter
2003
Prediction and measurement of an autoregulatory genetic module
Isaacs FJ, Hasty J, Cantor CR, Collins JJ. Prediction and measurement of an autoregulatory genetic module. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 7714-7719. PMID: 12808135, PMCID: PMC164653, DOI: 10.1073/pnas.1332628100.Peer-Reviewed Original ResearchConceptsGene regulatory networksGenetic modulesGene networksRegulatory networksComplex gene regulatory networksPhenotypic cellular responsesAutoregulatory gene networksStochastic versionCellular processesExpression statesProtein destabilizationCellular controlModel fluctuationsGene expressionSystems biologyCellular responsesProper quantitative descriptionQuantitative agreementSuch networksInternal noiseQuantitative descriptionQuantitative understandingKey propertiesPopulation distributionExperimental validation