Dr Michelle Dunstone
ARC Future Fellow
Telephone: +61 3 9902 9269
Facsimile: +61 3 9905 5645
Office: Room 244, Level 2, Building 77
Structural and bioinformatic studies of pore forming toxins and pathogen virulence factors.
Hole punchers: Pore Forming Proteins
I am fascinated with how pore forming proteins recognise their target cell, come together and then punch a hole into the cell. Here is a video of how the MACPF/CDC pore forming toxins work.
These pore forming proteins are used by the animal immune system to kill pathogenic bacteria, virally infected cells and cancerous cells (Law, Nature, 2010). And bacteria use the same tools to kill our cells (Reboul, PLoS Comp Biology, 2014). They are also used by fungi to defend themselves against bacteria and nematodes (Lukoyanova, PLoS Biology, 2015) and animal venoms (Ellisdon, PNAS, 2015). In fact there are a lot of unknown functions of pore forming proteins.
Here is how the immune system uses the Membrane Attack Complex (MAC) to attack a bacteria. My latest research in Nature Communications (Dudkina, Nat Comm, 2016) unravels how the MAC assembles in a specific way in order to target bacteria with variable membrane surfaces.
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.
I use X-ray crystallography, cryo-electron microscopy, computational biology and biophysics to answer these questions from the atomic level through to the cellular level.
The awesome team behind the research
Students interested in my lab can apply for an available department scholarship.
Please contact Dr. Michelle Dunstone for more information (email@example.com)
Career highlights of the work I have led
Dudkina, N.V., Spicer, B., Conroy, P., Reboul, C.F., Lukoyanova, N., Elmlund, H.O., Law, R.H.P., Ekkel, S., Kondos, S., Goode, R.J.A., Ramm, G., Whisstock, J.C., Saibil, H.R., Dunstone, M.A., 2016, Structure of the poly-C9 component of the complement membrane attack complex, Nature Communications, vol 7, pp. 1-6.
Lukoyanova, N., Kondos, S.C., Farabella, I., Law, R.H.P., Reboul, C.F., Caradoc-Davies, T.T., Spicer, B., Kleifeld, O., Traore, D.A.K., Ekkel, S.M., Voskoboinik, I., Trapani, J.A., Hatfaludi, T.Z., Oliver, K., Hotze, E.M., Tweten, R.K., Whisstock, J.C., Topf, M., Saibil, H.R., Dunstone, M.A., 2015, Conformational changes during pore formation by the perforin-related protein pleurotolysin, PLoS Biology, vol 13, issue 2 (Art. No: e1002049), pp. 1-15.
Reboul, C.F., Whisstock, J.C., Dunstone, M.A., 2014, A new model for pore formation by cholesterol-dependent cytolysins, PLoS Computational Biology, vol 10, issue 8, pp. 1-15.
Reboul, C.F., Mahmood, K., Whisstock, J.C., Dunstone, M.A., 2012, Predicting giant transmembrane beta-barrel architecture, Bioinformatics, vol 28, issue 10, pp. 1299-1302.
Rosado, C.J., Buckle, A.M., Law, R.H.P., Butcher, R.E., Kan, W., Bird, C.H., Ung, K.S., Browne, K.A., Baran, K., Bashtannyk-Puhalovich, T.A., Faux, N.G., Wong, W., Porter, C.J., Pike, R.N., Ellisdon, A.M., Pearce, M.C., Bottomley, S.P., Emsley, J., Smith, A.I., Rossjohn, J., Hartland, E.L., Voskoboinik, I., Trapani, J.A., Bird, P.I., Dunstone, M.A., Whisstock, J., 2007, A common fold mediates vertebrate defense and bacterial attack, Science, vol 317, issue 5844, pp. 1548-1551.
Other key publications:
Ellisdon, A.M., Reboul, C.F., Panjikar, S., Huynh, K., Oellig, C.A., Winter, K.L., Dunstone, M.A., Hodgson, W.C., Seymour, J.E., Dearden, P.K., Tweten, R.K., Whisstock, J.C., McGowan, S., 2015, Stonefish toxin defines an ancient branch of the perforin-like superfamily, PNAS, vol 112, issue 50, pp. 15360-15365.
Leung C, Dudkina NV, Lukoyanova N, Hodel AW, Farabella I, Pandurangan AP, Jahan N, Pires Damaso M, Osmanović D, Reboul CF, Dunstone MA, Andrew PW, Lonnen R, Topf M, Saibil HR, Hoogenboom BW, 2014, Stepwise visualization of membrane pore formation by suilysin, a bacterial cholesterol-dependent cytolysin, Elife, 2;3:e04247.
Law, R.H.P., Lukoyanova, N., Voskoboinik, I., Caradoc-Davies, T.T., Baran, K., Dunstone, M.A., D'Angelo, M., Orlova, E.V., Coulibaly, F.J., Verschoor, S., Browne, K.A., Ciccone, A., Kuiper, M.J., Bird, P.I., Trapani, J.A., Saibil, H.R., Whisstock, J.C., 2010, The structural basis for membrane binding and pore formation by lymphocyte perforin, Nature, vol 468, issue 7322, pp. 447-451.