Associate Professor Jeffrey Harmer

Principal Research Fellow

Centre for Advanced Imaging

Overview

Present Position

I am an ARC Future Fellow at the Centre for Advanced Imaging and associated with the University of Oxford as a Senior Visiting Research Fellow.

Previous Positions

  • August 2007 to March 2013: Scientific Coordinator and Applications manager of the Centre of Advanced Electron Spin Resonance (CAESR) at the Oxford University, UK.
  • 2002-July 2007: Project leader (“Ober-assistent”) in the Physical Chemistry Department at the Swiss Federal Institute of Technology (ETH), Zürich. I was a project leader in the electron paramagnetic resonance group of Prof. Arthur Schweiger.
  • 1999-2002: Postdoctoral position at ETH, Zurich. In the group of Prof. Arthur Schweiger I used CW and pulse EPR as a tool to investigate the geometric and electronic properties of transition metal complexes.
  • 1996-1999: Doctor of Philosophy from the Chemistry Department of the University of Newcastle, Australia, Advanced Coal Characterization by Nuclear Magnetic Resonance. The project was funded by the Collaborative Research Centre for Black Coal Utilization and I was supervised by the University of Newcastle (Prof. Marcel Maeder), BHP Research Melbourne (Dr. Brian Smith) and Callcott Coal Consulting (Dr. Tom Callcott).
  • 1995: Researcher at BHP Central Research Laboratories, Newcastle, Australia. I developed experimental techniques to measure the conductivity and the permeability of coal as it pertains to coke ovens.
  • 1992-1995: Researcher at Oakbridge Research Center, Newcastle, Australia. I worked on high temperature Nuclear Magnetic Resonance (NMR) for coal characterization (for my Bachelor of Science Honors thesis). This was a collaboration between the CSIRO Coal and Energy Division (North Ryde, Sydney), Oakbridge Research Centre and the University of Newcastle.

Keywords

structural biology · protein interactions · metalloenzymes · metal complexes · electron transfer · Iron sulphur clusters · pulse EPR · CW EPR · DEER · PELDOR ·HYSCORE · ENDOR · ESEEM · density functional theory · molecular dynamics

Research Interests

  • Electron Paramagnetic Resonance (EPR) spectroscopy in biological, medical, chemical and physical sciences.
    My main research field is Electron Paramagnetic Resonance (EPR) spectroscopy, a technique that probes the interaction of unpaired electrons with their surroundings. Paramagnetic centres are intrinsic to many systems and materials, for example biomolecules may contain metal clusters (e.g. [2Fe-2S]), transition metals (e.g. Cu, Fe, Mn, Ni) or organic radicals. Paramagnetic centres can also be attached to specific points in diamagnetic materials, as for example with the MTLS molecule that contains a nitroxide radical which is extensively used in site-directed spin labelling of biomolecules. A powerful technique of modern EPR is dipolar spectroscopy which is utilised in structural studies of biomolecules, for example with soluble and membrane proteins and their oligomers, DNA and RNA. Here dipolar spectroscopy refers to the measurement of electron-electron couplings with techniques such as Double Electron-Electron Resonance (DEER) or synonymously pulsed electron double resonance (PELDOR), double-quantum EPR (DQ-EPR), and related EPR methods. These EPR techniques can very accurately measure the dipole interaction between unpaired electron spins which enables the distance between them and their relative orientation to be determined. Owing to the large magnetic moment of the electron, the technique delivers information in the distance range from ca. 15-80 Å. From a set of such measurements a structural model of the system under investigation can be developed. For example DEER studies deliver information on protein conformational changes on ligand binding, and enable the investigation of protein-protein complexes and oligomers in frozen solution. The standard paramagnetic spin-label for dipolar spectroscopy is MTLS which is covalently attached to a protein via a disulfide bond with a cysteine residue, although there are a number of other organic labels and a number employing Cu2+ and Gd3+ ions for example. Possibilities also exist to attach spin-labels via other amino acids. DNA and RNA studies are also readily amendable to dipolar spectroscopy technologies. My area of research encompasses the characterization of structure-function relationships of biomolecules and their complexes, which includes development of the methodologies to measure electron-electron couplings and distances, the development of improved data analysis algorithms, and the development of modelling the sparse set of EPR constrains into 3D structures (for example using rigid-body docking, molecular dynamic simulations, etc.). Unpaired electrons are also coupled to nearby nuclear spins (e.g. 1H, 14N, 13C, 31P) and these couplings provide information in the distance range ca. <10 Å from the unpaired electron(s). Structural and electronic information of the paramagnetic centre from experiments is obtained with multi-frequency continuous wave (CW) EPR, and multi-frequency pulse EPR techniques such as electron nuclear double resonance (ENDOR), electron spin-echo envelope spectroscopy (ESEEM), and hyperfine sublevel correlation spectroscopy (HYSCORE). The experimentally measured EPR couplings describe the samples electronic structure as they relate in a direct way to the spin density distribution and thus single occupied molecular orbital. EPR couplings allow for example the identification of the type of nucleus, provide a description of the coordination environment in metal complexes, in metalloenzyme locate a substrate bound too or near the active site, and enable the identification of organic radicals. To aid in the interpretation of the experimental data extensive use of quantum chemistry calculations is used to further characterise the system under investigation.

Qualifications

  • Bachelor of Science (Honours), University of Newcastle
  • Doctor of Philosophy, University of Newcastle

Publications

View all Publications

Supervision

  • Doctor Philosophy

  • Doctor Philosophy

  • Doctor Philosophy

View all Supervision

Publications

Book

Book Chapter

  • Harmer, Jeffrey, Mitrikas, George and Schweiger, Arthur (2009). Advanced Pulse EPR Methods for the Characterization of Metalloproteins. In Lawrence Berliner and Graeme Hanson (Ed.), High Resolution EPR: Applications to Metalloenzymes and Metals in Medicine (pp. 13-61) New York , NY, U.S.A.: Springer New York. doi:10.1007/978-0-387-84856-3_2

Journal Article

Conference Publication

  • Harmer, J, Frison, G, Rudolph, M, Schonberg, H, Deblon, S, Maire, P, Boulmaaz, S, Breher, F, Bohler, C, Ruegger, H, Schweiger, A and Grutzmacher, H (2003). New perspectives for olefin complexes: Synthesis and characterisation of stable rhodium(0) and iridium(0) complexes. In: Perspectives in Organometallic Chemistry. 20th International Conference on Organometallic Chemistry (ICOMC), Corfu Greece, (222-239). Jul 07-12, 2002. doi:10.1039/9781847551641-00222

PhD and MPhil Supervision

Current Supervision

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Associate Advisor