Research units - Structural Biology
Structural Biology
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 offers the means to view the three-dimensional structure of proteins at the atomic level. Since majority of drugs interact with proteins, crystal structures have proved to be an invaluable starting point for the discovery of new drugs.
Research Overview
The work of the Biota Structural Biology Laboratory (BSBL) is internationally recognised with the determination of more than one hundred crystal 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 Biota, CSL Limited and the Cooperative Research Centre for Cancer Therapeutics.
Research Themes
Structural biology of cancer incorporating the ACRF Rational Drug Discovery Facility
Structural biology of infection
Honours and PhD Projects
Structural biology of proteins involved in cancer, infection and neurological diseases
Staff
Prof Michael Parker
Dr Brett Bennetts
Dr Michael Gorman
Dr Belinda Michell
Dr Luke Miles
Dr Craig Morton
David Ascher
Sophie Broughton
Matthew Chung
Gabriella Crespi
Dr Susanne Feil
Chen Gao
Nancy Hancock
Dr Jessica Holien
Dr Sara Lawrence
Dr Tracy Nero
Julian Tang
Dr Jerome Wielens
Publication Highlights
- 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.
- 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.
- Hu, S.H., Parker, M.W., Lei, J.Y., Wilce, M.C., Benian, G.M. & Kemp, B.E. (1994) Insights into autoregulation from the crystal structure of twitchin kinase. Nature 369, 581-584.
- Heierhorst, J., Kobe, B., Feil, S.C., Parker, M.W., Benian, G.M., Weiss, K.R. & Kemp, B.E. (1996) Ca2+/S100 regulation of giant protein kinases. Nature 380, 636-639.
- 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.
- Shatursky, O., Heuck, A.P., Shepard, L.A., Rossjohn, J., Parker, M.W., Johnson, A.E. & Tweten, R.K. (1999) The mechanism of membrane insertion for a cholesterol-dependent cytolysin: a novel paradigm for pore-forming toxins. Cell 99, 293-299.
- Gilbert, R.J., Jiménez, J.L., Chen, S., Tickle, I.J., Rossjohn, J., Parker, M., Andrew, P.W. & Saibil, H.R. (1999) Two structural transitions in membrane pore formation by pneumolysin, the pore-forming toxin of Streptococcus pneumoniae. Cell 97, 647-655.
- Cromer, B.A., Morton, C.J. & Parker, M.W. (2002) Anxiety over GABA(A) receptor structure relieved by AChBP. Trends Biochem. Sci. 27, 280-287.
- Brown, R.J., Adams, J.J., Pelekanos, R.A., Wan Y., McKinstry, W.J., Palethorpe, K., Seeber, R.M., Monks, T.A., Eidne, K.A., Parker, M.W. & Waters, M.J. (2005) Model for growth hormone receptor activation based on subunit rotation within a receptor dimer. Nature Struct. Mol. Biol. 12, 814-821.
- 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.