Ernest Laue

Ernest Laue

Chromatin remodelling and genome structure.

The Laue Group is interested in the way chromatin structure controls gene expression, and studies the structure and function of protein complexes involved in chromatin remodelling. 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.

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 and these are providing hypotheses regarding the function of the NuRD complex in regulating chromatin structure. In parallel, we are developing single-molecule microscopy to study the assembly of nuclear complexes in live cells.

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.

Research objectives

  • Super-resolution imaging and single cell Hi-C to study 3D genome organisation.

  • Single-molecule imaging to study how the NuRD complex affects chromatin structure and transcription factor binding.

  • Investigation of nucleosome remodelling by CHD4/NuRD.

Key publications

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

Lando D, Basu S, Stevens TJ, Riddell A, Wohlfahrt KJ, Cao Y, Boucher W, Leeb M, Atkinson LP, Lee SF, Hendrich B, Klenerman D, Laue ED (2018). Combining fluorescence imaging with Hi-C to study 3D genome architecture of the same single cell. Nat. Protoc., 13(5):1034-1061. doi: 10.1038/nprot.2018.017

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 (2016). The Nucleosome Remodeling and Deacetylase Complex NuRD is built from preformed catalytically active sub-modules. J. Mol. Biol., 428(14):2931-2942. doi: 10.1016/j.jmb.2016.04.025

Nagano T, Lubling Y, Stevens TJ, Schoenfelder S, Yaffe E, Dean W, Laue ED, Tanay A, Fraser P (2013). Single-cell Hi-C reveals cell-to-cell variability in chromosome structure. Nature, 502(7469):59-64. doi: 10.1038/nature12593