Elucidation of Structure-Function Relationships in Biological Systems Utilising Electron Paramagnetic Resonance Spectroscopy and Imaging.
Assoc Prof Harmer’s research focuses on high-resolution pulse Electron Paramagnetic Resonance (EPR) spectroscopy to determine molecular structure, dynamics and function of molecules containing unpaired electrons (paramagnetic materials). These molecules include the active sites of metalloenzymes, metal complexes, radicals, and diamagnetic proteins that have been spin labelled with small paramagnetic probes. Measurement of the electron-electron interaction (using e.g. DEER) provides accurate distance measurements in the unique range up to ca. 120 Å (the world record) which is well matched to determine biomolecule structure. Measurement of electron-nuclear interactions (e.g. using HYSCORE and ENDOR) enables the electronic and geometric structure around a paramagnetic centre to be characterised. These EPR techniques are being utilised for example to study substrate binding and recognition in cytochrome P450's (major drug metabolism & biosynthetic enzymes), and to understand the structure-function of the molecular machine NRPS which synthesis a diverse range of natural products with pharmaceutical applications (e.g. antibiotics, anti-cancer drugs). In additional to structural work at the molecular level, Dr Harmer’s research has a focus on in vivo EPR imaging and spectroscopy for studying the role of free radicals in ageing and age-related diseases, such as Parkinson's and Alzheimer's disease, using animal models.
Assoc Prof Jeffrey Harmer is an ARC Future Fellow and is associated with the University of Oxford as a Senior Visiting Research Fellow.
Keywords: structural biology • metalloenzymes • pulse EPR • DEER • molecular modelling
See the Harmer laboratory page for current group members.