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Ernest Laue

Chromatin assembly and genome structure

We are interested in the way chromatin structure controls gene expression, and study the structure and function of protein complexes involved in chromatin assembly. In particular, we focus on 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).

To understand how the NuRD complex modulates chromatin structure and gene expression we are developing an approach to combine single-molecule super-resolution imaging, to study nuclear complexes at near molecular resolution, with biochemical methods to study the global structure of chromatin within single cells. We have recently used this approach to calculate 3D structures of the intact genome in haploid embryonic stem cells (Stevens et al., Nature, 2017) and these are providing hypotheses regarding the function of the NuRD complex in regulating chromatin structure. In parallel, we are also developing single-molecule microscopy to study the assembly of nuclear complexes in live cells (Basu et al., Nature Commun., 2018).

To complement these studies, we are also carrying out structural studies of the NuRD complex. In the past we have principally used NMR spectroscopy and X-ray crystallography, but we are now increasingly using a combination of electron microscopy, chemical cross-linking/mass spectrometry and biophysical methods (Zhang et al., J. Mol. Biol., 2016).

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

 

Please visit the Laue Group Website for further details.

 

Key publications:

1. FRET-enhanced photostability allows improved single-molecule tracking of proteins and protein complexes in live mammalian cells, Basu S, Needham L-M, Taylor EJR, Wohlfahrt KJ, Lando D, Lagerholm BC, Tan YL, Bates L, Tkachenko O, Cramard J, Hendrich B, Eggeling C, Klenerman D, Lee SF, Laue ED. Nature communications, 2018,  9, 2520, doi:10.1038/s41467-018-04486-0, PMID:29955052

2. 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, PMID:28289288

3. 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, PMID:27117189