We are interested in the way chromatin structure controls epigenetic inheritance and study proteins and complexes involved in chromatin assembly/disassembly.
Our principal structural tools are NMR spectroscopy and X-ray crystallography, but we also use small-angle X-ray scattering, chemical cross-linking/mass spectrometry and biophysical methods to solve structural problems. Our current research is focussed on studies of two key protein complexes involved in chromatin structure; Chromatin Assembly Factor-1 (CAF-1), which assembles histones H3/H4 into DNA in the first step of nucleosome assembly, and the Nucleosome Remodelling Deacetylase complex (NuRD).
To complement our structural studies, we are developing approaches based on super-resolution fluorescence microscopy to directly image proteins involved in chromatin assembly and disassembly during DNA replication. This involves using molecular and cell biological techniques to tag particular proteins with photo-activatable fluorophores in order to study these proteins in live cells at the single molecule level. Finally, we are also using data from cross-linking and high-throughput sequencing to determine in-vivo chromosome structure in single cells.
Our research is funded by the Wellcome Trust and the EU 4DCellFate project. In addition, we founded and continue to play a key role in the CCPN project, a collaborative computing project for the NMR community.
Lab members: Liam Atkinson, Srinjan Basu, Wayne Boucher, Tom Drury, Maikel Fransen, David Lando, Andal Murthy, Edward Taylor, Aleksandra Watson, Kai Wohlfahrt, Wei Zhang
1. Single-cell Hi-C reveals cell-to-cell variability in chromosome structure. T. Nagano, Y. Lubling, T. J. Stevens, S. Schoenfelder, E. Yaffe, W. Dean, E. D. Laue, A. Tanay, P. Fraser, Nature, 2013, 502: 59-64
2. Structural plasticity of histones H3–H4 facilitates their allosteric exchange between RbAp48 and ASF1, Zhang W, Tyl M, Ward R, Sobott F, Maman J, Murthy AS, Watson AA, Fedorov O, Bowman A, Owen-Hughes T, EL-Mkami H, Murzina NV, Norman D, Laue ED, Nat Struct Mol Biol, 2013, 20 (1): 29-U43
3. Quantitative single-molecule microscopy reveals that CENP-A(Cnp1) deposition occurs during G2 in fission yeast, Lando D, Endesfelder U, Berger H, Subramanian L, Dunne PD, McColl J, Klenerman D, Carr AM, Sauer M, Allshire RC, Heilemann M, Laue ED, Open Biol, 2012, 2 (7): 120078