The Bode EPR lab

Research projects

Research in the Bode EPR lab is centred on EPR method development and applications. The latter range from biological systems and biomimetic model compounds to inorganic chemistry and catalysis.

The research is truly inter-disciplinary, embracing inorganic and organic synthesis of model systems, preparation of biological samples, experimental continuous wave (cw) and pulse EPR, numerical simulations, DFT calculations, etc.

A set of representative research projects in the Bode EPR lab is detailed below.

Information published on the university research information system can be found here.

1) Pulsed electron-electron double resonance (PELDOR)

Many (but not all) of our projects involve EPR distance measurements using the PELDOR/DEER method.

Many projects in the Bode lab are shared with in-house collaborators, such as structural biologists in the BSRC, or synthesis groups in Chemistry. Often, EPR spectroscopy is used to tackle questions where none of the more 'standard' physicochemical techniques is feasible. We embrace and strongly support this diversity.

Published examples of our work include research on the single-stranded DNA binding protein (SSB) of Sulfolobus solfataricus, a collaboration with Prof. M.F. White and Dr. J.C. Penedo. Using EPR distance measurements we could support the hypothesis that the protein does not form a significant amount of dimers (or even higher oligomers) without the presence of DNA.

In another study we looked at at the dimerisation interface of influenza A NS1 protein using EPR and molecular modelling.

BSRC collaboration on membrane channel proteins

This collaboration with Prof. J.H. Naismith, FRS and Dr. Christos Pliotas is centred on bacterial membrane channel proteins, with a focus on mechanosensation. The aim is to study structural changes between the different functional states (open/closed) of the protein multimers using different mutants exhibiting varying changes in between the states.

Another aspect of this collaboration is methodological development. EPR distance measurements in multi-spin systems are more involved than 2-spin systems and require further studies for a better understanding of how the difficulties encountered can be overcome. We study these systems in silico (simulations), using synthetic model systems, and investigating alternative procedures from sample preparation to data analysis.

This project has received funding from the EPSRC (First Grant).

This work has been co-funded by the Euopean Union Seventh Framework Programme.

BSRC and CMR collaboration on M3 protein

This project is about a surface protein called M3 from Streptococcus pyogenes. So far, there is very little structural information available on this protein which escapes crystallisation attempts and cannot be used full-length for NMR spectroscopy. With EPR, we try to elucidate specifically the binding site of the protein, which is supposed to bind to collagen as a dimer, thereby structural changes within the binding region are expected.

The project in collaboration with Dr. U. Schwarz-Linek has received funding from the MRC.

b) Methodology

We are engaged in methodology development using small-molecule chemical model systems (yardsticks; biomimetic systems) and numerical simulations.

Some of our methodology-related projects are described below.

Multi-spin synthetic model systems

Processing of PELDOR data is far more complicated in multi-spin systems than in 2-spin systems. We are developing a holistic approach to study these multi-spin systems under optimised conditions. This includes all steps from sample preparation, setting up the PELDOR experiment, to data analysis. Effective suppression of multi-spin effects and reliable determination of (intra-monomer) distances are our focus. The ultimate aim is the transfer to complex biomacromolecules.

This project has received funding from the EPSRC (First Grant).

Metal-nitroxide complexes

Such complexes allow in theory the determination of both, the nitroxide-nitroxide and the metal-nitroxide distance. Only paramagnetic metal ions can be targeted by EPR spectroscopy, however this is not trivial. We are working on chemically synthesised model compounds that form complexes with metal ions. Here, all distances are known in advance, and that the exact composition of the metal-ligand solution is controllable. This project may help studying metalloproteins by EPR.

This project was supported with a fully-funded PhD position by the EPSRC-funded doctoral training centre in integrated magnetic resonance (iMR).

2) Catalysis

Another aspect of research in the Bode lab is centred on the use of EPR for catalysis. Here, the full range of EPR methodology from continuous wave EPR to a variety of pulse experiments is employed.

Cr complexes in ethylene tetramerisation

Selective ethylene tetramerization to 1-octene using Cr complexes has attracted significant interest due to its wide range of applications in industry as precursors. It can be used for the production of low density polyethylene, surfactants, lubricants and elastomers. In this project our aim is to understand in-depth the mechanism of undergoing reactions via study of relevant paramagnetic species using in-situ EPR.

This PhD project is undertaken in collaboration with SASOL.