| Staff Listings |
Dr Michelle Dunstone
NHMRC Peter Doherty Fellow
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Telephone: +61 3 9902 9269
Facsimile: +61 3 9902 9500
Office: Room 231, Level 2, Building 77
Email: michelle.dunstone@med.monash.edu.au
Research Interests
Structural and bioinformatic studies of pore forming toxins and pathogen virulence factors.
Molecular Holepunchers: From Immunity To Bacterial Disease
In collaboration with Professor James Whisstock and Dr Ruby Law
Pore Forming Toxins (PFTs) are proteins commonly identified as bacterial virulence factors, proteins of the immune system and animal venoms (Rosado et al., Cellular Microbiology, 2008). These molecules possess the ability to change shape from water soluble single proteins to lipid membrane inserted ring-shapes consisting of 12 - 50 molecules. These ring-shapes act as pores in the target cell membrane that can result in death of the cell by lysis or delivery of other toxins. My lab focuses on the function of a recently united CDC/MACPF superfamily of pore forming toxins (Rosado et al., Science, 2007).
Model of how the MACPF protein domain is able to change shape. The red and yellow loops represent the region that can insert into the cell membrane thereby forming holes in the cell.
Projects: Projects on pore forming toxins aim to determine the pore structure of MACPF/CDC toxins. Comparison of the structures before and after pore formation will provide insight into the mechanism of function of all MACPF/CDC pore forming toxins in both disease and immunity. Lab skills taught include bioinformatics, molecular biology, protein chemistry, X-ray crystallography, cell lysis assays and cysteine fluorescence labelling studies.
http://en.wikipedia.org/wiki/Macpf
Structural Studies of the “Burger Bug”
In collaboration with Dr Elizabeth Hartland (Department of Immunology and Microbiology, University of Melbourne)
Information for Potential Students
If you have an interest in studying one of these projects please feel free to contact Michelle at anytime.
Selected Publications
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C.J. Rosado, S. Kondos, T.E. Bull, M.J. Kuiper, R.H.P. Law, A.M. Buckle, I. Voskoboinik, P.I. Bird, J.A.Trapani, J.C. Whisstock* and M.A. Dunstone* "The MACPF / CDC family of pore forming toxins." Cellular Microbiology (In press, 2008).
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C.J. Rosado, A.M. Buckle, R.H.P. Law, R.E. Butcher, W. Kan, C.H. Bird, K. Ung, K.A. Browne, K. Baran, T.A. Bashtannyk-Puhalovich, N.G. Faux, W. Wong, C.J. Porter, R.N. Pike, A.M. Ellisdon, M.C. Pearce, S.P. Bottomley, J. Emsley, A.I. Smith, J. Rossjohn, E.L. Hartland, I. Voskoboini, J.A. Trapani, P.I. Bird, M.A. Dunstone* and J.C. Whisstock$ "A common fold mediates vertebrate defense and bacterial attack." Science 317(5844):1548-51 (2007).
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F.M. Sansom, P. Riedmaier, H.J. Newton, M.A. Dunstone, C.E. Müller, H. Stephan, E. Byres, T. Beddoe, J. Rossjohn, P.J. Cowan, A.J. d'Apice, S.C. Robson, E.L. Hartland. "Enzymatic properties of an ecto-nucleoside triphosphate diphosphohydrolase from Legionella pneumophila: substrate specificity and requirement for virulence." Journal of Biological Chemistry 283(19) 12909-18 (2008).
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M.A. Dunstone*, C.S. Clements*, W.A. Macdonald, J. McCluskey and J. Rossjohn. "Specificity on a knife-edge: the alphabeta T cell receptor." Current Opinion in Structural Biology 16(6) 787-95 (2006).
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M.A. Dunstone*, L. Kjer-Nielsen*, L. Kostenko, L.K. Ely, T. Beddoe, N.A. Mifsud, A.W. Purcell, A.G. Brooks, J. McCluskey and J. Rossjohn. "Crystal structure of the human T cell receptor CD3 epsilon gamma heterodimer complexed to the therapeutic mAb OKT3."
Proceedings of the National Academy of Sciences USA 101(20) 7675-80 (2004).
