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| General Overview |
| | My main research interest is the delicate interplay between protein structure, dynamics and folding with protein function - by itself and embedded in the context of the whole metabolism of a living organism. I study these relationships with nuclear magnetic resonance (NMR) spectroscopy and a variety of other biochemical and biophysical techniques.
Individual research projects are outlined in further detail below. |
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| Research Overview
Structure, Dynamics, Folding and Function of Proteins in the Metabolic Context of the Cell |
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| 2005
| Interaction of Plant Proteinase Inhibitors with Insect Proteinases |
| | Lepidopteran insect pests are reponsible for significant losses of a range of crops, including cotton. Generally, plants counteract these attacks with proteinase inhibitors against the digestive enzymes of predatory insects. My aim is to characterise the interactions between the major digestive enzymes of the predatory Lepidopteran cotton pest Helicoverpa punctigera and plant proteinase inhibitors in atomic detail by structural, dynamic and biochemical studies. The outcomes of this project will lead to novel approaches to protect cotton and other economically important crops from present and future pests.
Collaborators:This project is in collaboration with A/Prof Marilyn Anderson (La Trobe University, Melbourne) and Hexima Ltd. (Melbourne). |
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| Helicoverpa
Helicoverpa punctigera feeding on cotton |
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| Keywords: | NMR spectroscopy, X-ray crystallography, protein structure, proteinase inhibitors |
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| 2005
| Structural Biology and Biophysical Characterisation of Dsb Proteins |
| | Protein folding is a major unsolved problem in biology. We focus on how proteins fold in the cell by studying the Dsb family of proteins that catalyse protein folding through disulfide bond oxidation, reduction or isomerisation. We use structural biology, biochemistry and biophysics to investigate the function of Dsb proteins. Our research will provide new insights into the process of protein folding in vivo and ultimately could lead to the development of more efficient biotechnology approaches for heterologous protein expression for research and medical applications.
Collaborators: A/Prof Jenny Martin, Dr Begoņa Heras |
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| DsbA
Thiol-disulfide oxidoreductase DsbA from E. coli |
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| Keywords: | protein folding, protein structure |
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| 2005
| NMR Metabonomics |
| | We want to understand how external triggers, such as drugs, illness, mutations etc., influence and change the metabolism of a subject. We study these metabolic changes by investigating the chemical composition of biofluids with NMR spectroscopy. Changes in the metabolic profile of e.g. urine are studied by multivariate statistical analysis and let us pinpoint, which parts of the subject's metabolism are disturbed. Thus, we can draw conclusions on the mechanism of action of the original trigger.
Current projects involve the study of the effects of growth hormone receptor mutations in mice, the mechanism of phosphine resistance in C. elegans, as well as several projects aimed at developing NMR metabonomics as a tool for clinical diagnosis.
Collaborators: Dr Agnieszka Lichanska, Dr Gary Leong, Dr Paul Ebert |
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| PCA
NMR Metabonomic Principal Components Analysis |
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| Keywords: | metabonomics, NMR spectroscopy, obesity, growth disorders |
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| 1999
| Folding and Packaging of Multidomain Proteinase Inhibitors from Nicotiana alata |
| | The aim of this project is to investigate the mechanisms of folding, processing and packaging of proteinase inhibitor modules in the multidomain protein ProPI from Nicotiana alata using NMR spectroscopy and X-ray crystallography. This protein, involved in defence against insects and other pathogens, may be compared to multiple warheads in missiles. It has multiple functional domains joined by cleavable linker regions and uses only one set of transport machinery for the ultimate delivery of several destructive weapons. The protein is unique in that the structural domains are offset with respect to the sequence repeats of the inhibitor gene as a result of intramolecular domain swapping. Consequently, the individual inhibitor domains are circular permutations of the sequence repeats.
Collaborators:A/Prof Marilyn Anderson (La Trobe University, Melbourne). |
| Keywords: | protein structure, NMR spectroscopy, protein folding, domain swapping |
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| 2001
| Structural Biology of Plant Defensins |
| | Plant defensins are small disulfide-rich proteins that exhibit antifungal and antimicrobial activity. The proteins are structurally conserved and have the fold of a cysteine-stabilised alpha-beta motif. In addition, the N- and C-terminus of plant defensins are linked by a disulfide bridge. I am studying a new class of plant defensins with an additional fifth disulfide bridge. Studies aim at elucidating the structural and functional role of this disulfide bridge.
Collaborators:A/Prof Marilyn Anderson (La Trobe University, Melbourne). |
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| Plant Defensin
Plant Defensin NaD1 protecting Nicotiana alata flowers |
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| Keywords: | protein structure, NMR spectroscopy |
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| 2001
| Structural Biology of Small Proteinase Inhibitors |
| | Sunflower trypsin inhibitor-1 (SFTI-1) is a cyclic peptide of 14 amino acids. The peptide is the smallest know Bowman-Birk inhibitor of proteinases, and with a sub-nanomolar Ki for trypsin also the strongest. The structure of the protein is highly stabilised by the cyclic peptide backbone, a disulfide bridge and an extensive network of hydrogen bonds. SFTI-1 exhibits the same structure in free form and in complex with trypsin. This minimisation of the entropic loss upon binding explains the high binding affinity. |
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| SFTI-1
Sunflower trypsin inhibitor 1 |
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| Keywords: | protein structure, NMR spectroscopy, proteinase inhibitors |
