A high brilliance X-ray generator with CCD detector for the Manchester Interdisciplinary Biocentre

Lead Research Organisation: University of Manchester
Department Name: Life Sciences

Abstract

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Technical Summary

The Manchester Interdisciplinary Biocentre (MIB: http:www.mib.ac.uk) is a new type of university research institute that will enable our academic community to explore key areas of interdisciplinary bioscience. It has been specifically designed to foster a scientific culture in which there are no barriers between the disciplines, thus ensuring that the widest possible range of expertise and techniques can be brought to bear on important bioscience problems. The purpose of this application is to finish the MIB with a state of the art x-ray set which is optimally configured to support the challenging structural biology research projects which will be conducted in the MIB. The MIB is purpose built to accommodate facilities for laser optics, nuclear magnetic resonance spectrometry, x-ray crystallography, electron microscopy, mass spectrometry and microfabrication, as well as electronic and mechanical workshops on the ground floor. Other floors will house further facilities, including those for biomolecular analysis, biocomputing, metabolomics, proteomics, chemical synthesis, robotics, genomics and single molecule research. Five major research themes will be pursued: (i) biocatalysis, (ii) biomolecular structure and dynamics, (iii) bioanotechnology, (iv) biophotonics and bioelectronics and (v) systems biology. In direct support of the biomolecular structure and dynamics activity the MIB will house high field NMR spectrometers, and an electron microscopy suite. X-ray crystallography facilities are needed to complete the spectrum of biophysical techniques. The structural biology community at MIB will include the crystallographers Leys, Conn, Derrick and Prince who have joint projects with Scrutton, Munro, Micklefield, Kell, McCarthy, Flitsch and Turner. The recent addition of Leys, Scrutton, Munro, Flitsch and Turner has created urgent need for the provision of a routine x-ray source in-house for MIB to provide for suitable infrastructure and support for both ongoing (BBSRC funded) and future structural biology projects. The present lack of dedicated x-ray source at MIB will seriously hamper the ongoing development and competitiveness of this highly successful grouping. The applicants have already obtained a considerable amount of BBSRC funding for several structural biology projects. An array of challenging crystallographic problems are being addressed by the applicants here including membrane protein structure, RNA structure and translation and structural enzymology. Projects here are congruent with BBSRC panel priority areas such as BIOMIS, MENZ, PROLIN, COMBIOSYS and POPMOP from the BMS committee and chemical biology, multiprotein complexes from the BCB committee. The application is also compatible with cross committee priority areas such as drug resistance and alternatives to chemotherapeutics, biophysics and bioscience engineering. The x-ray facility will allow researchers in the MIB to underpin their research with the rigour of structural biology and enhance collaboration between the various strands of structural biology giving added value, for example by addressing the structure and dynamics of large multi-protein complexes using a combination of disciplines. The research projects listed in support of our application attract synchrotron beamtime allocations (to SRS, Daresbury, ESRF Grenoble, DESY Hamburg), the availability of a user-friendly local facility will greatly increase the efficiency of usage of these allocations by bringing more routine experiments in-house and allowing the pre-screening of crystals. The present use of our synchrotron allocation time for screening of crystals is highly inefficient and likely to result in negative repercussions on future beamtime allocations. The provision of an x-ray facility for the MIB will therefore satisfy a pressing need and produce excellent value for investment over and above the substantial discount on the equipment agreed by the manufacturer.

Publications

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Dixon N (2010) Reengineering orthogonally selective riboswitches in Proceedings of the National Academy of Sciences

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Gilbert RJ (2007) Reconfiguration of yeast 40S ribosomal subunit domains by the translation initiation multifactor complex. in Proceedings of the National Academy of Sciences of the United States of America

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Stevenson AL (2008) Found in translation: another RNA helicase function. in Molecular cell

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Tait S (2010) Local control of a disorder-order transition in 4E-BP1 underpins regulation of translation via eIF4E. in Proceedings of the National Academy of Sciences of the United States of America

 
Description This equipment has been used for multiple projects in the Manchester Interdisciplinary Biocentre, primarily to determine whether crystals are capable of producing good diffraction data. Crystals selected on the basis of these results have generally been taken to a synchrotron for full analysis and subsequent structure determination.
Exploitation Route To my knowledge, the equipment continues to be used as a source of preliminary diffraction data. I have not been at the MIB since 2010.
Sectors Chemicals,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology