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).
Research
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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.
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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.
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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.
Publications
Our most recent publications below, visit PubMed for more...
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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.
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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.
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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.
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Reyes-Lamothe R,Nicolas E, Sherratt D. (2012)
Chromosome Replication and Segregation in Bacteria.
Annu Rev Genet. 2012 Dec 15;46:121-143.
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Badrinarayanan A, Lesterlin C, Reyes-Lamothe R, Sherratt D. (2012)
The Escherichia coli SMC complex, MukBEF, shapes nucleoid organization independently of DNA replication.
J Bacteriol. 2012 Sep;194(17):4669-76.
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Männik J, Wu F, Hol FJ, Bisicchia P, Sherratt DJ, Keymer JE, Dekker C. (2012)
Robustness and accuracy of cell division in Escherichia coli in diverse cell shapes.
Proc Natl Acad Sci U S A. 2012 May 1;109(18):6957-62.
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Lee JY, Finkelstein IJ, Crozat E, Sherratt DJ, Greene EC. (2012)
Single-molecule imaging of DNA curtains reveals mechanisms of KOPS sequence targeting by the DNA translocase FtsK.
Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6531-6.
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Tran T, Andres P, Petroni A, Soler-Bistué A, Albornoz E, Zorreguieta A, Reyes-Lamothe R, Sherratt DJ, Corso A, Tolmasky ME. (2012)
Small plasmids harboring qnrB19: a model for plasmid evolution mediated by site-specific recombination at oriT and Xer sites.
Antimicrob Agents Chemother. 2012 Apr;56(4):1821-7.
→ For more listed on PubMed.
People
Research associate postdocs...
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Dr.
Paola Bisicchia
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Dr.
Sophie Nolivos
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Dr.
Amy Upton
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Dr.
Stephan Uphoff
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Dr.
Jakob Schweizer
Technical staff...
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Mrs.
Rachel Baker
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Mrs.
Katarzyna Zawadzka
Recent former lab members...
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Dr.
Pawel Zawadzki
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Dr.
Estelle Crozat
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Dr.
Apurba Koner
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Dr.
Anjana Badrinarayanan
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Dr.
Emilien Nicolas
Pictures
Contact
Enquiries with CV welcome. For postdoc or graduate student positions, please contact Prof. David Sherratt directly.
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Prof David Sherratt
Iveagh Professor of Microbiology Lab: +44 (0)1865 613234
Office: +44 (0)1865 613237
Fax: +44 (0)1865 613238
david.sherratt@bioch.ox.ac.uk -
Microbiology Unit
Department of Biochemistry
University of Oxford
South Parks Rd, Oxford
OX1 3QU, UK