We are interested in the way chromatin structure controls epigenetic inheritance, and study proteins and complexes involved in chromatin assembly/disassembly. Our current research is focussed on studies of the Nucleosome Remodelling Deacetylase complex (NuRD), which plays a key role in controlling the differentiation of embryonic stem (ES) cells and the reprogramming of adult cells to a pluripotent state (capable of differentiating into all the different types of cell/tissue).
Our principal structural tools are NMR spectroscopy and X-ray crystallography, but we also use small-angle X-ray scattering, electron microscopy, chemical cross-linking/mass spectrometry and biophysical methods to solve structural problems. 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. This involves using molecular and cell biological techniques to tag particular proteins with photo-activatable fluorophores in order to study these proteins in fixed and 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, the Medical Research Council and the EU 4DCellFate project.
Please visit the Laue G for further details.
1. 3D structure of individual mammalian genomes studied by single cell Hi-C. Stevens TJ, Lando D, Basu S, Atkinson LP, Cao Y, Lee SF, Leeb M, Wohlfahrt KJ, Boucher W, O’Shaughnessy-Kirwan A, Cramard J, Faure AJ, Ralser M, Blanco E, Morey L, Sansó M, Palayret MGS, Lehner B, Di Croce L, Wutz A, Hendrich B, Klenerman D, Laue ED. Nature, 2017, doi: 10.1038/nature21429
2. The Nucleosome Remodeling and Deacetylase Complex NuRD is built from preformed catalytically active sub-modules. Zhang W, Aubert A, Gomez de Segura JM, Karuppasamy M, Basu S, Murthy AS, Diamante A, Drury TA, Balmer J, Cramard J, Watson AA, Lando D, Lee SF, Palayret M, Kloet SL, Smits AH, Deery MJ, Vermeulen M, Hendrich B, Klenerman D, Schaffitzel C, Berger I, Laue ED. Journal of Molecular Biology, 2016, 428(14): 2931-42
3. 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