Award details

Facilities for automated structural proteomics

Reference	REI20513
Principal Investigator / Supervisor	Dr John Rafferty
Co-Investigators / Co-Supervisors	Professor Peter Artymiuk, Dr Patrick Baker, Professor David Rice
Institution	University of Sheffield
Department	Molecular Biology and Biotechnology
Funding type	Research
Value (£)	86,039
Status	Completed
Type	Research Grant
Start date	01/02/2004
End date	31/01/2005
Duration	12 months

Abstract

Knowledge of protein structure is essential to underpin the ongoing drive in proteomics as we seek to benefit from genome sequencing initiatives. Currently the rate of protein crystal structure determination is limited by the number of crystallisation experiments that can be performed on a given sample of highly purified material. This number can be both time and resource limited and thus methods that can be speed up and more efficiently utilise samples will greatly aid the process. The methodology of high throughput screening via robotics, developed largely by the pharmaceutical industry for its assay protocols, is now starting to revolutionise macromolecular crystallisation procedures. This approach complements initiatives in other areas for the production of pure proteins (e.g. BBSRC BMS committee RAGES priority area) and data acquisition (e.g. Research Council funding for protein crystallography beamlines at the new DIAMOND synchrotron facility). The research carried out in the structural biology group in Sheffield covers a wide range of projects and areas of great strength and depth include the analysis of essential proteins for survival of Gram +ve organisms (B. subtilis, S. aureus), targeting of key enzymes in parasites (P. falciparum, T. gondii) and the complex multi-component protein-DNA machinery involved in replication, recombination and transcription. All of these areas have a major underlying theme of contributing to the development of novel chemotherapeutic agents. Our efforts in determining protein-nucleic acid structures, and the inhibitor complexes that provide the rationale for the support of our external sponsor and much of the additional industrial funding, also fit BBSRC initiatives on protein-ligand interactions (PROLIN). This work requires multi-component combinations and wide-ranging screens usually using limited precious supplies of inhibitors, for which the the ability to improve protein production and use samples in a highly efficient manner during crystallisation is paramount. The equipment for which support is requested will greatly facilitate these ends. The Biostat fermenter provides a robust system but with sensitive control of growth parameters from the foremost manufacturer. Consultation with manufacturers, studies of published data and experience of other laboratories embarking on robotic methods for crystallisation have suggested that the partnership of the Robbins Hydra for plate preparation and the Cartesian Microsys for nanolitre protein dispensing are currently the best available and the most cost effective combination for the tasks that we require. They will ensure that the structural biology at Sheffield continues its ground-breaking and internationally competitive research.

Summary

unavailable

Committee	Closed Committee - Biomolecular Sciences (BMS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	Research Equipment Initiative 2003 (RE2) [2003]
Funding Scheme	X – not Funded via a specific Funding Scheme

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