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Details of Grant 

EPSRC Reference: GR/R28713/01
Title: Spatial Mapping of Biomolecular Surface Physiochemical Properties at Sub-Molecular Resolution
Principal Investigator: Roberts, Professor C
Other Investigators:
Williams, Dr P Atherton, Dr J Hardie, Dr KR
Tendler, Professor S Williams, Professor PM Moriarty, Professor PJ
Hunt, Dr MRC
Researcher Co-Investigators:
Project Partners:
Department: Sch of Pharmaceutical Sciences
Organisation: University of Nottingham
Scheme: Standard Research (Pre-FEC)
Starts: 10 December 2001 Ends: 09 December 2004 Value (£): 241,077
EPSRC Research Topic Classifications:
Chemical Biology Surfaces & Interfaces
EPSRC Industrial Sector Classifications:
Environment Pharmaceuticals and Biotechnology
Related Grants:
Panel History:  
Summary on Grant Application Form
The recent development of nanotube atomic force microscope (AFM) probes has significantly increased the spatial resolution achievable on biomolecular systems. Exploiting our expertise in probe microscopy, chemically specific AFM analysis and new approaches to data analysis and validation we propose to develop a novel generic approach, which will allow the direct measurement and mapping of the surface topography and physico-chemical properties of individual biomolecules at sub-molecular resolution. One key outcome of the work will be the ability to address the problem of mapping the interaction surface between macromolecules, a matter of fundamental and applied importance across biology, biotechnology and the pharmaceutical sciences.Technology will be developed to reproducibly manufacture functionalized nanotube AFM probes. Proof of principle application of such probes will be provided upon model micro-patterned substrates and protein systems. We will then image and map surface molecular properties of the protein Cytotoxin Vac A from Helicobacter pylori (native, mutant and recombinant) in prokaryotic membranes and during interaction with eukaryotic outer membranes. A further advance will be the ability to analyse isolated oligomers of VacA. The use of real time analysis while altering conditions, especially pH, will enable definition of the structural basis underlying conformational changes, especially acid activation of VacA.
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Further Information:  
Organisation Website: http://www.nottingham.ac.uk