Parker laboratory: Structural biology and computational Design

• Professor Michael Parker

  Head of Laboratory and Director, Bio21 Institute

  mwp@unimelb.edu.au
  +61 3 83442211

Research Overview

Proteins are one of the body's most essential building blocks and are the molecular engines that control all functions of the body. X-ray crystallography and cryo-electron-microscopy offers the means to view the three-dimensional structure of proteins at the atomic level. Since the majority of drugs interact with proteins, atomic structures have proved to be invaluable for the discovery and development of new drugs.

The work of our laboratory is internationally recognised with the determination of more than two hundred crystal and cryo-EM structures including those of membrane-associating proteins, detoxifying enzymes and protein kinases. This work has provided insights into a number of diseases such as cancer, bacterial and viral infections, and neurological diseases such as Alzheimer's disease. In recent years we have been emphasising the translational aspects of our work with an increasing focus on structure-based drug discovery. This focus has been underpinned by the development of virtual screening and fragment screening platforms in-house, by funding from the Australian Cancer Research Foundation, and partnerships with a number of Biotechnology companies including CSL Limited and Janssen.

Keywords: Protein structure, X-ray crystallography, Cryo electron microscopy, Structure-based drug design, Cancer, Alzheimer’s Disease, Bacterial toxins

Staff

Cynthia Chen, Honours Student
Dr Michelle Christie, Post-doctoral Fellow
Gabriela Crespi, Research Assistant
Dr Larissa Doughty, Post-doctoral Fellow
Marialena Georgopoulou, PhD Student
Dr Michael Gorman, Post-doctoral Fellow
Nancy Hancock, Research Assistant
Dr Stefan Hermans, Post-doctoral Fellow
Riya Joseph, PhD student
Mitali Kulkani, Research Assistant
Dr Nas Meftahi, Post-doctoral Fellow
Dr Tracy Nero, Post-doctoral Fellow
Mary-Anne Schimdt, Laboratory Manager
Dr David Teran, Post-doctoral Fellow
Dr Andrew Tsatsanis, Post-doctoral Fellow
Dr Emma Van Der Westhuizen, Laboratory Manager and Post-doctoral Fellow
Dr Claire Weekley, Post-doctoral Fellow

Research Publications

Click here for the results of a Google Scholar analysis of Michael's publications.

Click here for the results of a PubMed search of Michael's publications.

1. Parker, M.W., Pattus, F., Tucker, A.D. & Tsernoglou, D. (1989) Structure of the membrane-pore-forming fragment of colicin A. Nature 337, 93-96.
2. Parker, M.W., Buckley, J.T., Postma, J.P., Tucker, A.D., Leonard, K., Pattus, F. & Tsernoglou, D. (1994) Structure of the Aeromonas toxin proaerolysin in its water-soluble and membrane-channel states. Nature 367, 292-295.
3. Rossjohn, J., Feil, S.C., McKinstry, W.J., Tweten, R.K. & Parker, M.W. (1997) Structure of a cholesterol-binding, thiol-activated cytolysin and a model of its membrane form. Cell 89, 685-692.
4. Hansen, G., Hercus, T.R., McClure, B.J., Stomski, F.C., Dottore, M., Powell, J., Ramshaw, H., Woodcock, J.M., Xu, Y., Guthridge, M., McKinstry, W.J., Lopez, A.F. & Parker, M.W. (2008) The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation. Cell 134, 496-507.
5. Baell, J.B., Leaver, D., Cleary, B., Nguyen, N., Downer, L.D., Vanyai, H.K., Bergamasco, M.I., May, R.E., Wang, B., Wilcox, S., Garnham, A., Pacini, G., Zamudio, N., Sheikh, B.N., Doggett, K., Mieruszynski, S., Heath, J.K., Chung, M.C., Hermans, S.J., Parker, M.W., de Silva, M., Lagiakos, H.R., Bentley, J., Pilling, P., Hattarki, M., Dolezal, O., Falk, H., Smyth, G.K., Street, I.P., Monahan, B.J., Peat, T.S., Voss, A.K. & Thomas, T. (2018) Selective inhibition of MYST lysine acetyltransferases leads to cellular senescence in a KAT6-dependent mode. Nature 560, 253-257.
6. Miles, L.A., Hermans, S., Crespi, G.A.N., Gooi, J.H., Doughty, L., Nero, T.L., Markulić, J., Ebneth, A., Wroblowski, B., Oehlrich, D., Trabanco, A.A., Rives, M-L., Royaux, I., Hancock, N.C., & Parker, M.W. (2019) Small molecule binding to Alzheimer's risk factor CD33 promotes Aβ phagocytosis. iScience 19, 110-118.
7. De Luca, A., Parker, L.J., Han, A.W., Rodolfo, C., Gabbarini, V., Hancock, N.C., Palone, F., Mazzetti, A.P., Menin, L., Morton, C.J., Parker, M.W., Lo Bello, M. & Dyson, P. (2019) A structure-based mechanism of cisplatin resistance mediated by Glutathione Transferase P1-1. Proc. Natl. Acad. Sci. USA 116, 13943-13951.
8. Zeller, J., Cheung Tung Shing, K.S., Nero, T.L., McFadyen, J.D., Krippner, G., Bogner, B., Kreuzaler, S., Kiefer, J., Horner, V.K., Braig, D., Danish, H., Baratchi, S., Fricke, M., Wang, X., Kather, M.G., Kammerer, B., Woollard, K.J., Sharma, P., Morton, C.J., Pietersz, G., Parker, M.W., Peter, K. & Eisenhardt, S.U. (2023) A novel phosphocholine-mimetic inhibits a pro-inflammatory conformational change in C-reactive protein. EMBO Mol. Med. 15, e16236.
9. Kan, W.L., Dhagat, U., Kaufmann, K.B., Hercus, T.R., Nero, T.L., Zeng, A.G.X., Toubla, J., Barry, E.F., Broughton, S.E., Gomez, G.A., Benard A.B., Dottore, M., Cheung Tung Shing, K.S., Boutzen, H., Samaraweera, S.E., Simpson, K.J., Jin, L., Goodall, G.J., Begley, C.G., Thomas, D., Ekert, P.G., Tvorogov, D., D'Andrea, R.J., Dick, J.E., Parker M.W. & Lopez A.F. (2023) Distinct assemblies of heterodimeric cytokine receptors govern stemness programs in leukemia. Cancer Discovery 13, 1922-1947.
10. Johnstone, B.A., Christie, M.P., Joseph, R., Morton, C.J., Brown, H.G., Hanssen, E., Sanford, T.C., Abrahamsen, H.L., Tweten, R.K. & Parker, M.W. (2025) Structural basis for the pore-forming activity of a complement-like toxin. Sci. Adv. 11, eadt2127.