Research in the Sherratt group is aimed at understanding how DNA replication, recombination and chromosome segregation shape bacterial chromosome organization in the context of the living cell.
The research observes where genes and molecular machines are positioned as a cell proceeds through its growth and division cycles, and what happens when normal cellular behaviour is perturbed by different methods. Individual components of DNA organizing and processing machines are studied genetically, structurally and biochemically, and information on their molecular action is integrated into the context of their action in cells.
Model of FtsK C-terminal domain with hexameric motor (blue) and trimeric gamma-subdomain (yellow) bound to KOPS (red).
Chromosome dynamics - tracking genetic loci in space and time
Gene position can be followed in space and time in living cells. Genetic loci are tracked by simultaneous binding of fluorescent repressors to the arrays of their cognate operators inserted into the chromosome regions of interest. Chromosome organization and segregation are also studied in relation to E. coli SMC proteins MukBEF and divisome components, such as FtsZ and FtsK.
Replisome dynamics - DNA replication, block and restart
The dynamics of the replication machinery (replisome) is studied by labeling replisome components with fluorescent proteins at the normal chromosome locus. Replisome dynamics is also studied in relation to chromosome segregation and cell division. Fluorescent repressor-operator arrays are also used to study reversible replication fork blockage and restart at a specific locus.
Site-specific recombination and DNA translocase FtsK
FtsK belongs to a family of DNA translocases involved in the acquisition of foreign genes during conjugation and in segregation of chromosomes during spore formation and cell division. In E. coli, FtsK acts at the last stage of chromosome segregation and controls the resolution of chromosome dimers. This latter activity is achieved in combination with site-specific recombinases XerCD acting at dif.
Our most recent publications below.
Nicolas E, Upton AL, Uphoff S, Henry O, Badrinarayanan A, Sherratt D. (2014)
The SMC complex MukBEF recruits topoisomerase IV to the origin of replication region in live Escherichia coli.
MBio. 2014 Feb 11;5(1):e01001-13.
Lesterlin C, Ball G, Schermelleh L, Sherratt DJ. (2013)
RecA bundles mediate homology pairing between distant sisters during DNA break repair.
Nature. 2014 Feb 13;506(7487):249-53.
Bisicchia P, Arumugam S, Schwille P, Sherratt D. (2013)
MinC, MinD, and MinE drive counter-oscillation of early-cell-division proteins prior to Escherichia coli septum formation.
MBio. 2013 Dec 10;4(6):e00856-13.
Bisicchia P, Steel B, Mariam Debela MH, Löwe J, Sherratt D. (2013)
The N-terminal membrane-spanning domain of the Escherichia coli DNA translocase FtsK hexamerizes at midcell.
MBio. 2013 Dec 3;4(6):e00800-13.
Shimokawa K, Ishihara K, Grainge I, Sherratt DJ, Vazquez M. (2013)
FtsK-dependent XerCD-dif recombination unlinks replication catenanes in a stepwise manner.
Proc Natl Acad Sci U S A. 2013 Dec 24;110(52):20906-11.
Reyes-Lamothe R, Tran T, Meas D, Lee L, Li AM, Sherratt DJ, Tolmasky ME. (2013)
High-copy bacterial plasmids diffuse in the nucleoid-free space, replicate stochastically and are randomly partitioned at cell division.
Nucleic Acids Res. 2013 Oct 16. [Epub ahead of print]
Nolivos S, Sherratt D. (2013)
The bacterial chromosome: architecture and action of bacterial SMC and SMC-like complexes.
FEMS Microbiol Rev. 2013 Oct doi: 10.1111/1574-6976.12045.
Uphoff S, Reyes-Lamothe R, Garza de Leon F, Sherratt D, Kapanidis AN. (2013)
Single-molecule DNA repair in live bacteria.
Proc Natl Acad Sci U S A. 2013 May 14;110(20):8063-68.
Sherratt D. (2013)
Plasmid partition: sisters drifting apart.
EMBO J. 2013 May 2;32(9):1208-10.
Upton AL, Sherratt DJ. (2013)
Breaking symmetry in SMCs.
Nat Struct Mol Biol. 2013 Mar;20(3):246-9.
Koner AL, Krndija D, Hou Q, Sherratt DJ, Howarth M. (2013)
Hydroxy-terminated conjugated polymer nanoparticles have near-unity bright fraction and reveal cholesterol-dependence of IGF1R nanodomains.
ACS Nano. 2013 Feb 26;7(2):1137-44.
Pinkney JNM, Zawadzki P, Mazuryk J, Arciszewska LK, Sherratt D, Kapanidis AN. (2012)
Capturing reaction paths and intermediates in Cre-loxP recombination using single-molecule fluorescence.
Proc Natl Acad Sci U S A. 2012 December 18;109(51):20871-76.
Badrinarayanan A, Reyes-Lamothe R,Stephan Uphoff, Mark C. Leake and Sherratt D. (2012)
In Vivo architecture and action of bacterial Structural Maintenance of Chromosome Proteins.
Science. 2012 Oct;338:528-531.
→ For more listed on PubMed.
Research associate postdocs
Recent former lab members
Enquiries with CV welcome. For postdoc or graduate student positions, please contact Prof. David Sherratt directly.
Prof David Sherratt
Iveagh Professor of Microbiology
Lab: +44 (0)1865 613234
Office: +44 (0)1865 613237
Fax: +44 (0)1865 613238
Department of Biochemistry
University of Oxford
South Parks Rd, Oxford
OX1 3QU, UK