Science | David Waterman

David Waterman Microfocus MX

David Waterman is a Post Doctoral Research Associate for the MX beamlines, working with Gwyndaf Evans. Prior to joining Diamond, he completed a PhD at the York Structural Biology Laboratory (University of York) investigating the structure and function of prokaryotic RNA-binding proteins and developing target selection strategies for structural genomics.

Email: david.waterman@diamond.ac.uk
Tel: +44 (0) 1235 778722
Beamline I04: Macromolecular Crystallography

Key Research Areas

Structural biology, macromolecular crystallography, processing of diffraction data, bioinformatics.

Current Research Interests

The field of macromolecular crystallography has grown rapidly in recent years, in part driven by the contributions from structural genomics and associated high-throughput technologies, but also from the success of increasingly ambitious projects tackling the structures of large biological complexes, complete viral particles and traditionally difficult targets such as membrane proteins. In order to facilitate the speed at which new structures are determined it is often necessary to work with crystals that are small, difficult to handle, or produce weak diffraction. Nevertheless, the quality of diffraction data is of the utmost importance, especially for phasing methods that use accurately measured anomalous diffraction differences.

The   structure  of   B.  anthracis  ThiI,   a tRNA thiouridine synthase, co-crystallised with  AMP  bound  at  the  active  site.

We intend to address outstanding issues with the treatment of measurement errors present with the type of CCD detectors most often used for macromolecular crystallography. Physical processes within these detectors lead to spatial correlations that are currently not dealt with accurately. By developing software to enable a proper treatment of measurement statistics, it is hoped that a better understanding of the properties of such detectors can be achieved, ultimately resulting in an improvement in recorded diffraction data.

I also have a continuing interest in the structure and function of RNA binding proteins, which are involved in some of the most conserved and important processes of the biochemistry of life, such as the core functions of transcription and translation as well as regulation, processing, modification and degradation of the myriad of RNAs found in cellular lifeforms. For example, RNA molecules often contain various post-transcriptional modifications that alter their biophysical properties in ways that increase their stability, improve the fidelity of translation and change their specificities for binding partners.

Although approximately 100 such chemical modifications have been detected to date, the mechanisms of many of the enzymes responsible remain elusive, and many lack any structural and biochemical characterisation. We have identified sets of tRNA modifying enzymes for structural determination by bioinformatics methods and plan to subject these to the structure solution ‘pipeline’, encompassing protein production, purification, crystallisation and structure solution by X-ray crystallography. A more thorough investigation of the properties of RNA binding proteins and their complexes with RNA will help to clarify the mechanisms involved in RNA metabolism, and lead to a better understanding of interactions between RNA and protein.

Selected Publications

1. "Crystal structure of Mil (Mth680): internal duplication and similarity between the Imp4/Brix domain and the anticodon-binding domain of class IIa aminoacyl-tRNA synthetases.", C Ng, DG Waterman, EV Koonin, AA Antson, M Ortiz-Lombardia, EMBO Rep 6(2): 140-6. (2005)
2. "Application of high-throughput technologies to a structural proteomics-type analysis of Bacillus anthracis.", K Au, N Berrow, E Blagova, I Boucher, M Boyle, J Brannigan, L Carter, T Dierks, G Folkers, R Grenha, K Harlos, R Kaptein, A Kalliomaa, V Levdikov, C Meier, N Milioti, O Moroz, A Muller, R Owens, N Rzechorzek, S Sainsbury, D Stuart, T Walter, D Waterman, A Wilkinson, K Wilson, N Zaccai, R Esnouf, M Fogg, Acta Crystallographica Section D 62(10): 1267-1275. (2006)
3. "Crystal Structure of Bacillus anthracis ThiI, a tRNA-modifying Enzyme Containing the Predicted RNA-binding THUMP Domain", DG Waterman, M Ortiz-Lombardia, MJ Fogg, EV Koonin, AA Antson, J Mol Biol 356(1): 97-110. (2006)