Iron is the most abundant element on earth and one of the most abundant in the earth’s crust. Due to its high availability before the introduction of oxygen-producing organisms, it has been suggested that life started with iron (Günter Wächtershäuser). This also explains why iron based chemistry lies at the heart of all life. Iron has a broad redox chemistry and therefore it is used in oxidation catalysis and bioenergetics but is also used in acid-base reactions.
Our group wishes to understand how iron-oxygen reactivity is attained and regulated in the body and through this develop knowledge that is essential for understanding both physiological and pathophysiological processes. This will increase knowledge of iron-oxygen reactivity in both chemistry and biology.
Standard molecular biology and protein purification techniques allow us to express and purify enzymes of interest. We use a range of fast-flow techniques, including stopped-flow, chemical quench and freeze-quench to investigate the rates of reactions and to isolate intermediates. Spectroscopic characterisation is though Mössbauer, EPR and NMR.
We also use Mössbauer spectroscopy to investigate a wide range of compounds from nanoparticles to coordination polymers and from proteins to whole cells. We run a low temperature system in Bio21 and interested and happy to collaborate with anybody that might find this technique useful. Please contact firstname.lastname@example.org for more information.
Currently, we have two main research projects:
- Thiol dioxygenation. Thiol dioxygenases are a class of iron containing enzymes that catalyse the oxidation of thiols to the corresponding sulfinates. These enzymes are found in practically all forms of life including plants, bacteria, fungi and higher organisms. This work is carried out in collaboration with a number of people, in particular structural work with Sigurd Wilbanks at Otago University. To truly understand both the spectroscopic signatures and the underlying reasons for observed differences in reactivity at the atomic level, carrying out biochemical and small molecule model chemistry hand-in-hand provides both incredible strength and novelty. Small molecule models made by David Goldberg at Johns Hopkins University provide invaluable information. Sam de Visser at Manchester University calculates mechanisms and spectroscopic signals that we can compare with experiment.
- Peroxidases. Peroxidases use hydrogen peroxide to catalyse very important chemical transformations. Lactoperoxidase is a heme containing enzyme that is part of the innate immune system and plays a key role in host defence by oxidizing thiocyanate to the bactericidal agent hypothiocyanite. It is present in saliva, milk and other fluids. In particular we are interested in understanding how lactoperoxidase reactivity can be regulated by physiologically relevant small molecules. This work is in collaboration with Tony Kettle at Otago University, Christchurch. Peroxidase activity of cytochrome c is studied with Liz Ledgerwood of Otago University.
- Understanding how cells store and use iron. This project aims to understand the mechanism and function of the protein nanocage, ferritin, which stores iron in the body ready for use on demand. Iron is an essential element, vital for wellbeing. To understand iron we need to understand ferritin. Despite being widely studied, how ferritin actually works remains unclear. This project aims to use an interdisciplinary approach combining protein biochemistry, spectroscopy, genetics and whole organism studies. It will develop new techniques to enable the physiological role of iron to be explored. Outcomes of this innovative platform are anticipated to include in-depth understanding of how ferritin functions to unravel its fundamental role in iron storage and release ready for re-use. This project is in collaboration with Gawain McColl of the Florey and funded by the ARC.