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Ernest Laue

Structural studies of chromatin assembly/disassembly

We are interested in the way chromatin structure controls epigenetic inheritance, and study proteins and complexes involved in chromatin assembly/disassembly. We focus on biochemical and structural studies of protein complexes involved in controlling chromatin structure such as the Nucleosome Remodelling and Deacetylase (NuRD) complex, 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). Recently, we have developed single molecule tracking approaches to study nuclear proteins at near molecular resolution, in live cells, using photo-activated light microscopy (PALM). In parallel, we have also pioneered computational approaches to study the global structure of chromatin within single cells. We have recently used these approaches to calculate structures of the intact genome in haploid embryonic stem cells (Stevens et al., Nature, 2017) and these structures are providing hypotheses regarding the function of the NuRD complex in regulating chromatin structure.

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 use super-resolution fluorescence microscopy, which 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 also use data from cross-linking and high-throughput sequencing to determine in-vivo chromosome structure in single cells.

Our research is currently funded by the Wellcome Trust and the Medical Research Council.

 

Please visit the Laue Group Website for further details.

 

Key publications:

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