Departmental homepageProfessor Laue is a physical chemist based in the Department of Biochemistry. He develops methods for structural studies of proteins and protein complexes. During the last ten years, Laue has explored the feasibility of determining structures of whole chromosomes and genomes using a combination of super-resolution imaging and single nucleus Hi-C (snHi-C) experiments, inspired by protein structure determination using NMR spectroscopy, building on his expertise in scientific computational software development (developed while establishing an international community-wide open-source software development project for NMR spectroscopy (CCPN, www.ccpn.ac.uk)).
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, they focus on the Nucleosome Remodelling and Deacetylase (NuRD) complex, which plays a key role in controlling the differentiation of embryonic stem (ES) cells. To understand how the NuRD complex modulates chromatin structure and gene expression, they 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 3D structure of chromatin within single cells. They have recently used this approach to calculate 3D structures of the intact genome in haploid embryonic stem cells and these are providing hypotheses regarding how enhancer-promoter interactions are reorganised and genes are switched on/off in the early stages of differentiation. In parallel, they are developing single-molecule microscopy to study the assembly and dynamics of nuclear complexes in live cells.
Enhancer-promoter interactions are reconfigured through the formation of long-range multiway hubs as mouse ES cells exit pluripotency. Lando D, Ma X, Cao Y, Jartseva A, Stevens TJ, Boucher W, Reynolds N, Montibus B, Hall D, Lackner A, Ragheb R, Leeb M, Hendrich BD, Laue ED. Mol Cell. 2024 Apr 18;84(8):1406-1421.e8. Epub 2024 Mar 14. PMID: 38490199
Live-cell three-dimensional single-molecule tracking reveals modulation of enhancer dynamics by NuRD. Basu S, Shukron O, Hall D, Parutto P, Ponjavic A, Shah D, Boucher W, Lando D, Zhang W, Reynolds N, Sober LH, Jartseva A, Ragheb R, Ma X, Cramard J, Floyd R, Balmer J, Drury TA, Carr AR, Needham LM, Aubert A, Communie G, Gor K, Steindel M, Morey L, Blanco E, Bartke T, Di Croce L, Berger I, Schaffitzel C, Lee SF, Stevens TJ, Klenerman D, Hendrich BD, Holcman D, Laue ED. Nat Struct Mol Biol. 2023 Nov;30(11):1628-1639. Epub 2023 Sep 28. PMID: 37770717
3D structures 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 Apr 6;544(7648):59-64. Epub 2017 Mar 13. PMID: 28289288
Single-cell Hi-C reveals cell-to-cell variability in chromosome structure. Nagano T, Lubling Y, Stevens TJ, Schoenfelder S, Yaffe E, Dean W, Laue ED, Tanay A, Fraser P. Nature. 2013 Oct 3;502(7469):59-64. Epub 2013 Sep 25. PMID: 24067610
