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The University of Southampton
Structural Biology Part of Biological Sciences

Method development

Developing new methods and technologies is key to driving science forward and achieving novel results. New methods are being developed here at Southampton and in conjunction with the Diamond Light Source synchrotron facility near Oxford.

Solid-State NMR Method Development

Extracting new information locked up in the naturally abundant 14N nucleus
Novel 14N NMR of proteins

Solid-state NMR is a powerful technique that can provide valuable structural and dynamic information at the molecular level about biological systems that are largely intractable to other structural biology techniques. Driven by challenges biology we are developing novel experimental approaches together with our colleagues in Chemistry to provide novel methods for the characterisation of biological materials. Two areas which we are actively researching are:

1. Enhancing sensitivity through the use of cryogenic magic-angle spinning and paramagnetic relaxation agents. These studies seek to identify novel ways to enhance the sensitivity of solid-state NMR through the use of low temperature measurements. Coupled with research into paramagnetic reagents which can enhance the speed with which measurement can be performed, and potentially provide structural information, we aim to realise significant enhancement in sensitivity.

2. 14 N solid-state NMR of biomolecules. In nature the most abundant isotope of nitrogen is nitrogen-14. Traditionally however, studies of biomolecules by NMR has relied on nitrogen-15 labelling. This precludes the analysis of biological materials where labelling is not available and results in the loss of a wealth of structural and dynamic data which is present in the nitrogen-14 spectrum. We are currently developing a range of techniques that permit the analysis of nitrogen sites within biomolecules, environmental samples and pharmaceuticals where previously labelling would have been viewed as a pre-requisite.

PhD: James Jarvis
Supervisor: Dr Phil Williamson
PhD Research: 14 N characterisation in solid state protein NMR
Funding: University Scholarship
Primary research group: Molecular and Cellular Biosciences

PhD: Michael Jolly
Supervisor: Dr Phil Williamson
PhD Research: Biological cryogenic MAS NMR
Funding: EPSRC , Integrated Magnetic Resonance Centre for Doctoral Training
Primary research group: Molecular and Cellular Biosciences

X-ray Crystallography Development

The University of Southampton is a partner in the VMX proposal in the Diamond Light Source (co-applicant Ivo Tews). The aim of this proposal is to create a sub-micron, high flux density beam-line with variable focus as x-ray source for challenging microcrystals, as well as an automated station for in situ data collection. Proposal , Scientific poster .

The University of Southampton is represented at the Macromolecular Village Working Group at the Diamond Light Source and supports the proposal for the UK to join the Serial Femtosecond Crystallography (SFX) consortium for the first dedicated macromolecular crystallography beamline at an X-ray Free Electron Laser.

The software suite CCP4 bundles programmes for crystallographic structure analysis. Ivo Tews is a member of CCP4 working group 1 and chairs working group 2 . The most recent CCP4 study weekend has been organized by Ivo Tews (Southampton) and Jon Cooper (UCL).

PhD: Matthew Rodrigues
Supervisors: Dr Ivo Tews , Dr Gwyndaf Evans
PhD research: Catching Reaction Intermediates in the Multi-step PLP biosynthesis with Microfocus Synchrotron Techniques in situ.
Funding: Diamond Light Source and University of Southampton
Primary research group: Molecular and Cellular Biosciences

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