{"entity": "researcher", "timestamp": "2026-09-24T16:52:07.954Z", "family": "Jones", "given": "Daniel Lawson", "initials": "DL", "orcid": "0000-0002-7902-996X", "affiliations": ["Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/c401a7245b154808804a202050385a53.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/c401a7245b154808804a202050385a53"}}, "publications": [{"entity": "publication", "iuid": "8e3a65fdcab64edf97f193b24269de23", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8e3a65fdcab64edf97f193b24269de23.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8e3a65fdcab64edf97f193b24269de23"}}, "title": "Anti-correlation of LacI association and dissociation rates observed in living cells.", "authors": [{"family": "Kandavalli", "given": "Vinodh", "initials": "V", "orcid": "0000-0001-9093-156X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bd4b803bba964f37854171fc2640f97b.json"}}, {"family": "Zikrin", "given": "Spartak", "initials": "S", "orcid": "0000-0002-7802-8869", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/712d42db7d5046bb83ed01ec797e9e09.json"}}, {"family": "Elf", "given": "Johan", "initials": "J", "orcid": "0000-0001-5522-1810", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7001138c10bf4a6d84075057ba30c8b9.json"}}, {"family": "Jones", "given": "Daniel", "initials": "D", "orcid": "0000-0002-7902-996X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c401a7245b154808804a202050385a53.json"}}], "type": "journal article", "published": "2025-01-17", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "16", "issue": "1", "pages": "764", "issn-l": "2041-1723"}, "abstract": "The rate at which transcription factors (TFs) bind their cognate sites has long been assumed to be limited by diffusion, and thus independent of binding site sequence. Here, we systematically test this assumption using cell-to-cell variability in gene expression as a window into the in vivo association and dissociation kinetics of the model transcription factor LacI. Using a stochastic model of the relationship between gene expression variability and binding kinetics, we performed single-cell gene expression measurements to infer association and dissociation rates for a set of 35 different LacI binding sites. We found that both association and dissociation rates differed significantly between binding sites, and moreover observed a clear anticorrelation between these rates across varying binding site strengths. These results contradict the long-standing hypothesis that TF binding site strength is primarily dictated by the dissociation rate, but may confer the evolutionary advantage that TFs do not get stuck in near-operator sequences while searching.", "doi": "10.1038/s41467-025-56053-z", "pmid": "39824877", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11748676"}, {"db": "pii", "key": "10.1038/s41467-025-56053-z"}], "notes": [], "created": "2026-09-23T12:27:35.687Z", "modified": "2026-09-23T12:27:35.758Z"}, {"entity": "publication", "iuid": "189dbcfd3afa46688103e6d73e69d61c", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/189dbcfd3afa46688103e6d73e69d61c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/189dbcfd3afa46688103e6d73e69d61c"}}, "title": "Kinetics of dCas9 target search in Escherichia coli.", "authors": [{"family": "Jones", "given": "Daniel Lawson", "initials": "DL", "orcid": "0000-0002-7902-996X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c401a7245b154808804a202050385a53.json"}}, {"family": "Leroy", "given": "Prune", "initials": "P", "orcid": "0000-0003-2855-1050", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/21ad088068124be48e8530292bc1e0af.json"}}, {"family": "Unoson", "given": "Cecilia", "initials": "C", "orcid": "0000-0002-2101-4079", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4d031e0944034d9b97edffdce2775414.json"}}, {"family": "Fange", "given": "David", "initials": "D"}, {"family": "\u0106uri\u0107", "given": "Vladimir", "initials": "V"}, {"family": "Lawson", "given": "Michael J", "initials": "MJ"}, {"family": "Elf", "given": "Johan", "initials": "J", "orcid": "0000-0001-5522-1810", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7001138c10bf4a6d84075057ba30c8b9.json"}}], "type": "journal article", "published": "2017-09-29", "journal": {"title": "Science (New York, N.Y.)", "issn": "1095-9203", "volume": "357", "issue": "6358", "pages": "1420-1424", "issn-l": "0036-8075"}, "abstract": "How fast can a cell locate a specific chromosomal DNA sequence specified by a single-stranded oligonucleotide? To address this question, we investigate the intracellular search processes of the Cas9 protein, which can be programmed by a guide RNA to bind essentially any DNA sequence. This targeting flexibility requires Cas9 to unwind the DNA double helix to test for correct base pairing to the guide RNA. Here we study the search mechanisms of the catalytically inactive Cas9 (dCas9) in living Escherichia coli by combining single-molecule fluorescence microscopy and bulk restriction-protection assays. We find that it takes a single fluorescently labeled dCas9 6 hours to find the correct target sequence, which implies that each potential target is bound for less than 30 milliseconds. Once bound, dCas9 remains associated until replication. To achieve fast targeting, both Cas9 and its guide RNA have to be present at high concentrations.", "doi": "10.1126/science.aah7084", "pmid": "28963258", "labels": [], "xrefs": [{"db": "mid", "key": "EMS79094"}, {"db": "pmc", "key": "PMC6150439"}, {"db": "pii", "key": "357/6358/1420"}], "notes": [], "created": "2018-12-05T11:04:24.651Z", "modified": "2026-09-23T06:45:49.547Z"}]}