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.
MukBEF organizes the chromosome
We study the architecture of MukBEF complexes with epifluorescence microscopy, Structured Illumination Microscopy (image above) and with super-resolution PALM microscopy. We are trying to understand how the interplay between MukBEF, Topoisomerase IV and MatP regulates the chromosome architecture and segregation.
DNA repair in living E. coli cells
We investigate mechanistic details of DNA repair in living bacteria cells using super-resolution microscopy. The pathways we are particularly interested in are: homologous recombination, methylation damage and nucleotide excision repair pathway.
Our most recent publications below.
Uphoff S, Sherratt DJ. (2017)
Single-Molecule Analysis of Bacterial DNA Repair and Mutagenesis.
Annu Rev Biophys. 2017 Mar 24 46:-
Stracy M, Jaciuk M, Uphoff S, Kapanidis AN, Nowotny M, Sherratt DJ, Zawadzki P. (2016)
Single-molecule imaging of UvrA and UvrB recruitment to DNA lesions in living Escherichia coli.
Nat Commun. 7:12568
Uphoff S, Lord D, Potvin-Trottier L, Okumus B, Sherratt DJ, Paulsson J (2016)
Stochastic activation of a DNA damage response causes cell-to-cell mutation rate variation.
Nolivos S, Upton AL, Badrinarayanan A, Müller J, Zawadzka K, Wiktor J, Gill A, Arciszewska LK, Nicolas E, Sherratt DJ (2016)
MatP regulates the coordinated action of topoisomerase IV and MukBEF in chromosome segregation
Nature Commun. 7:10466
Zawadzki P, Stracy M, Ginda K, Zawadzka K, Kapanidis AN, Sherratt DJ. (2015)
The Localization and Action of Topoisomerase IV in Escherichia coli Chromosome Segregation is Coordinated by the SMC Complex, MukBEF.
Cell Reports, 13: 2587-96.
May PF, Zawadzki P, Sherratt DJ, Kapanidis AN, Arciszewska LK (2015)
Assembly, translocation, and activation of XerCD-dif recombination by FtsK translocase analyzed in real-time by FRET and two-color tethered fluorophore motion.
Fleurie A, Lesterlin C, Manuse S, Zhao C, Cluzel C, Lavergne JP, Franz-Wachtel M, Macek B, Combet C, Kuru E, VanNieuwenhze MS, Brun YV, Sherratt D, Grangeasse C. (2014)
MapZ marks the division sites and positions FtsZ rings in Streptococcus pneumoniae.
Nature. 2014 Dec 11;516(7530):259-62.
→ For more listed on PubMed.
Enquiries with CV welcome. For postdoc or graduate student positions, please contact Prof. David Sherratt directly.
Prof David SherrattIveagh Professor of Microbiology
Lab: +44 (0)1865 613234
Office: +44 (0)1865 613237
Fax: +44 (0)1865 613238