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Dr Christine Hawkins
Murdoch Children's Research Institute at the Royal Children’s Hospital
University of Melbourne
Flemington Rd, Parkville, Vic 3052
Email: chris.hawkins@mcri.edu.au
Tel: +61-3-9345-5823
Fax: +61-3-9345-6524

Our research focuses on elucidating programmed cell death (apoptosis) pathways. Upon receipt of apoptotic stimuli, activation of the caspase family of cysteine proteases brings about the systematic dismantling of the cell, through proteolysis of a suite of cellular substrates. We are interested in the mechanisms by which caspases are activated and their activity is regulated. We previously developed two yeast-based systems for identifying and characterising caspases and their regulators. Yeast is an experimentally tractable eukaryote, lacking endogenous apoptotic signal transduction pathway components. Current projects exploit the yeast-based systems to screen for and characterise novel caspase inhibitors. We have also reconstituted metazoan apoptotic pathways in yeast and are using these reconstituted pathways to conduct mutagenesis experiments and to explore the evolutionary conservation of apoptotic pathways.
Many of our projects relate to the inhibition of caspases. Members of the p35 and IAP family can inhibit caspases, and we are exploring these inhibitory capabilities. We previously showed that, unusually, the distal insect caspase DRONC could cleave substrates following either aspartate or glutamate. Also atypically for caspases, while DRONC is susceptible to inhibition by a Drosophila IAP (DIAP-1), it is insensitive to p35 inhibition. We have recently characterised the second member of the p35 family, p49. Unlike p35, p49 was able to inhibit DRONC (in addition to most other caspases). We are currently studying the regulation of the activity of the mammalian enzyme Caspase-2.
David Vaux, Paul Ekert, John Silke and Anne Verhagen (The Walter and Eliza Hall Institute of Medical Research, Australia)

Michael Hengartner (Institute of Molecular Biology, University of Zurich, Switzerland)

Marty Dickman (University of Nebraska, USA)

Terry Johns (Ludwig Institute for Cancer Research, Austin & Repatriation Medical Centre, Australia)

Robin Anderson (The Peter MacCallum Cancer Institute, Australia)

Trevor Lithgow (University of Melbourne, Australia)
Hawkins, C.J.; Wang, S.L.; Hay, B.A.“A cloning method to identify caspases and their regulators in yeast: identification of Drosophila IAP1 as an inhibitor of the Drosophila caspase DCP-1”, Proc. Natl. Acad. Sci. 1999, 96: 2885-2890.

Hawkins, C.J.; Yoo, S.J.; Petersen, E.; Wang, S.L; Vernooy, S.Y; Hay, B.A. “The Drosophila caspase DRONC cleaves following glutamate or aspartate and is regulated by DIAP1, HID, and GRIM.”, J. Biol. Chem. 2000, 275, 27084-27093

Hawkins, C.J.; Wang, S.L.; Hay, B.A. “Monitoring the activity of caspases and their regulators in the yeast Saccharomyces cerevisiae”, Meth. Enz. 2000, 322, 162-174

Jabbour A.M.; Ekert, P.G.; Coulson, E.J.; Knight, M.J.; Ashley, D.M.; Hawkins, C.J. “The p35 relative, p49, inhibits mammalian and Drosophila caspases including DRONC and protects against apoptosis”, Cell Death Differ. 2002, 9, 1311-20

Jabbour, A.M.; Hawkins, C.J. “The p35 family of apoptosis inhibitors”, Current Genomics. 2004, In press.

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