James Nicholson
Macromolecular Crystallography

James Nicholson is a senior beamline scientist on the Macromolecular Crystallography Beamline I03. James joined Diamond in the Summer of 2010 having worked for twelve years (1996-2008) at the SRS, Daresbury Laboratory developing, managing and supporting protein crystallography and infrared microspectroscopy & imaging beamlines, followed by two years (2008-2010) as Laboratory Manager at the University of Liverpool CR-UK Cancer Research Centre.

Email: james.nicholson@diamond.ac.uk
Tel: +44 (0) 1235 778667
MX Beamlines

Key Research Areas

Macromolecular Crystallography, Chromatin Structure and Function, Histones

Research Interests

Chromatin Structure and Function

In collaboration with Liverpool John Moores, Liverpool and Sheffield Universities

Chromatin is the complex of proteins and DNA that control the cell cycle, DNA replication with histone assembly, DNA repair, the initiation of transcription and elongation in higher eukaryotes. The histone proteins package DNA in cell nuclei, by assembling as an octamer of one tetramer and two dimers, and modulate gene expression through an intricate combination of post-translational modifications (PTM). The high mobility group (HMG) proteins are some of the most abundant and important non-histone proteins that interact with the DNA-histone complexes that form nucleosomes and higher-order chromatin structures. HMG proteins play a significant role in remodelling chromatin and regulating gene expression by distorting, bending or modifying the DNA structure, which is bound to histones and transcription factors.

The acid (red)-base (blue) packing interaction of neighbouring histone octamers.

We have previously developed methods to extract pure intact core histones (dimers, tetramers and octamers), linker histones, HMGs and other chromatin-related molecules from small volumes of chicken blood and have recently developed the technology for human blood and plasma. The methods produce milligram yields of intact native proteins from a single blood donation and have been used to successfully crystallise and solve the chick histone octamer structure to 1.90 Å resolution.

Current research is focussed in two main areas: the identification of novel protein and PTM markers in diseased blood; and understanding the molecular mechanisms behind nucleosome remodelling through structure-function studies of histones and their complexes with other molecules.

Selected Publications

1. An Investigation of the RWPE Prostate Derived Family of Cell Lines Using FTIR Spectroscopy.
   M.J. Baker, C. Clarke, D. Démoulin, J. M. Nicholson, F. Lyng, H.J. Byrne, C.A. Hart, M.D. Brown, N.W. Clarke and P. Gardner.
   Analyst, (2010) 135, 887-894.

2. Tracking the cell hierarchy in the human intestine using biochemical signatures derived by mid-infrared microspectroscopy
   Michael J. Walsh, Azzedine Hammiche, Tariq G. Fellous, James M. Nicholson, Marine Cotte, Jean Susini, Nigel J. Fullwood, Pierre L. Martin-Hirsch, Malcolm R. Alison and Francis L. Martin.
   Stem Cell Research, (2009) 3, 15-27.

3. Derivation of a subtype-specific biochemical signature of endometrial carcinoma using synchrotron-based Fourier-transform infrared microspectroscopy.
   Jemma G. Kelly, Valon Llabjani, Maneesh N. Singh, Michael J. Walsh, James M. Nicholson, Fariba Bahrami, Katherine M. Ashton, Mark A. Pitt, David H. Phillips, Pierre L. Martin-Hirsch and Francis L. Martin.
   Cancer Letters, (2009) 274 (2), 208-217.

4. FTIR micro-spectroscopy identifies symmetric PO2- modifications as a marker of the putative stem cell region of human intestinal crypts.
   Michael J. Walsh, Tariq G. Fellous, Azzedine Hammiche, Nigel J. Fullwood, Olaug Grude, Fariba Bahrami, James M. Nicholson, Hubert M. Pollock, Mairi Brittan, Pierre L. Martin-Hirsch, Malcolm R. Alison and Francis L. Martin.
   Stem Cells, (2008). 26 (1), 108-118. 

5. Early stages of protein crystallization as revealed by emerging optical waveguide technology.
   Attia Boudjemline, David T. Clarke, Neville J. Freeman, James M. Nicholson and Gareth R. Jones.
   Journal of Applied Crystallography, (2008). 41 (3), 523-530.

6. Book: Chromatin Structure and Function.
   J.M. Nicholson and C.M. Wood (Editors) (2006). ISBN: 81-7895-234-3. Transworld Research Network.

7. The Oxidised Histone Octamer Does Not Form a H3 Disulphide Bond.
   C. M. Wood, S. Sodngam, J. M. Nicholson, S. J. Lambert, C. D. Reynolds and J. P. Baldwin.
   Biochimica et Biophysica Acta - Proteins and Proteomics, (2006). 1764 (8), 1356-1362. 

8. High-resolution structure of the native histone octamer.
   C. M. Wood, J. M. Nicholson, S. J. Lambert, L. Chantalat, C. D. Reynolds and J. P. Baldwin.
   Acta Crystallographica, F61, (2005), 541-545. 

9. Histone Structures: Targets for Modifications by Molecular Assemblies.
   Nicholson, J.M., Wood, C.M., Reynolds, C.D., Brown, A., Lambert, S.J., Chantalat, L. and Baldwin, J.P.
   Annals of the New York Academy of Sciences, 1030, (2004), 642-653.