My research interests revolve around the application and development of solution-state NMR techniques to address questions of structure, function, dynamics and interactions of molecules, specifically within the context of organic chemistry and chemical biology. Many of the projects in which I am involved arise through collaborations with groups across the Department, the University and beyond.
NMR Supersequences for efficient structure characterisation
We are developing families of time-efficient NMR "supersequences" we refer to as NOAH (NMR by Ordered Acquisition using 1H detection) that can provide a significant reduction in the time required for collecting 2D data sets used for the characterisation of small molecules and may also offer sensitivity benefits in some cases. These experiments function by nesting multiple conventional 2D experiments into one, thereby reducing the number of lengthy magnetisation recovery delays required in data acquisition. This work is in collaboration with Dr Eriks Kupce of Bruker Biospin UK.
Protein-ligand interactions and protein function probed by NMR Spectroscopy
The interaction of small molecules and peptides with protein targets is an area in which NMR spectroscopy plays a key role, providing information on the behaviour of the smaller molecule and on structural changes in the protein itself. We use a wide range of ligand-observe and protein-observe techniques to probe such interactions (such as relaxation filtering, saturation transfer difference, WaterLOGSY and chemical shift perturbation studies) and we apply these methods to a variety biological systems. Whilst much of or work involves ligand-observe techniques, we employ protein-observe methods when isotopically labelled macromolecules are available, for example via non-specific (backbone) 15N or specific (sidechain) 19F labelling. The protein systems we study have relevance to mechanisms of mammalian oxygen sensing, epigenetics and antibacterial resistance and arise from collaborations with Profs Chris Schofield (Chemistry), Akane Kawamura (Newcastle) and others.
In a collaboration with the group of Dr. Fay Probert (Chemistry), we apply NMR spectroscopy to metabolomics- the study of the complete metabolite profile in a biofluid or tissue- with a view to assisting in disease diagnosis and/or monitoring disease progression. We have applied this methodology to various conditions of interest to local clinical groups including multiple sclerosis and cancer, also in collaboration with Prof Daniel Anthony (Pharmacology) and Prof Niki Sibson (Oncology). NMR spectroscopy is well suited to such studies as it is robust, reproducible and inherently quantitative, as well as requiring minimal sample preparation. It complements the mass spectrometry metabolomics research program in the group of Prof James McCullagh (Chemistry).