About Dr Julianne Djordjevic
Cryptococcus neoformans is a common cause of invasive fungal infection, responsible for around one million cases of meningitis and 675,000 deaths per year in HIV-infected patients alone. In light of the scarcity of antifungal drug classes, the emergence of resistant fungi, and unfavourable toxicity profiles of key marketed antifungal drugs, the search for new drug targets is a major health priority. Our laboratory is interested in unravelling the complexities of virulence-related signalling and secretion pathways within this model pathogen, and in identifying novel potential targets within these pathways for antifungal drug design.
Julie Djordjevic is head of the fungal pathogenesis group within the Centre for Infectious Diseases and Microbiology, a research centre affiliated with the University of Sydney and based at the Westmead Millennium Institute (WMI), Westmead Hospital.
Using the AIDS-related pulmonary and neurotropic model pathogen, Cryptococcus neoformans, her laboratory is actively investigating mechanisms used by fungal pathogens to establish systemic infection in humans. The research focuses specifically on unravelling the complexities of virulence-related signal transduction and secretion pathways, and the team is actively engaged in collaborative research within Australia and overseas. The laboratory has hosted several PhD and honours students and is keen to continue fostering research-lead postgraduate teaching.
Summary of the team's key research findings include identification of:1. A role for Sec14p in virulence and secretion of specific fungal virulence determinants (phosphospholiase B) - evidence for the existence of more than one secretion pathway in C. neoformans
2. Specialized membrane subsets (rafts) and the cell wall as virulence factor reservoirs
3. A role for N-linked glycosylation & lipid anchoring in secretion of the common invasion (phospholipase B)
4. Phospholipase C1 as a central regulator of virulence and potential drug target
5. Fungal Cox9p as a molecular target of the anti-leishmanial drug, miltefosine.
2. Zuo, X., Djordjevic, J.T., Bijosono Oei, J., Desmarini, D., Schibeci, S.D., Jolliffe, K.A., & Sorrell, T.C. (2011), Miltefosine Induces Apoptosis-like Cell Death in Yeast via Cox9p in Cytochrome c Oxidase. Molecular Pharmacology, Epub ahead of print [PMID: 21610197]
3. Fox, D.S., Djordjevic, J.T., & Sorrell, T.C. (2011), Signaling cascades and enzymes as Cryptococcus virulence factors. In J. Heitman, T. Kozel, J. Kwon-Chung, et al (Eds.), Cryptococcus: From Human Pathogen to Model Yeast. (pp.217-234). Washington, DC: ASM Press.
4. Djordjevic, J.T. (2010), Role of Phospholipases in Fungal Fitness, Pathogenicity and Drug Development - Lessons from Cryptococcus neoformans (Review). Frontiers in Mycology, 1(125), 1-13
5. Gilbert, N.M., Donlin, M.J., Gerik, K.J., Specht, C., Djordjevic, J.T., Wilson, C.F., Sorrell, T.C. & Lodge, J.K. (2010), KRE genes are required for β-1,6-glucan synthesis, maintenance of capsule architecture and cell wall protein anchoring in Cryptococcus neoformans. Molecular Microbiology, 7(2), 517-534 [PMID: 20384682]
6. Panepinto, J., Komperda, K., Frases, S., Park, Y-D., Djordjevic, J.T., Casadevall, A. & Williamson, P.R. (2009), Sec6-dependent sorting of fungal extracellular exosomes and laccase of Cryptococcus neoformans. Molecular Microbiology, 71(5), 1165-1176. [PMID: 19210702]
7. Chayakulkeeree, M., Sorrell, T.C., Siafakas, A.R., Wilson, C.F., Pantarat, N., Gerik, K.J., Boadle, R. & Djordjevic J.T. (2008), Role and Mechanism of Phosphatidyl-inositol Specific Phospholipase C in Survival and Virulence of Cryptococcus neoformans. Molecular Microbiology, 69(4), 809-826. [PMID: 18532984]
8. Jones, P., Turner, K.M., Djordjevic, J.T., Sorrell, T.C., Wright, L.C. & George, A.M. (2007), Role of Conserved Active Site Residues in Catalysis by Phospholipase B1 from Cryptococcus neoformans. Biochemistry, 46(35), 10024-10032 [PMID: 17685590]
9. Siafakas, A.R., Sorrell, T.C., Wright, L.C., Wilson, C.F., Larsen, M., Boadle, R., Williamson, P.R. & Djordjevic, J.T. (2007), Cell Wall-Linked Cryptococcal Phospholipase B1 is a Source of Secreted Enzyme and a Determinant of Cell Wall Integrity. Journal of Biological Chemistry, 282(52), 37508-37514 [PMID: 17947228]
10. Siafakas, A.R., Sorrell, T.C., Wright, L.C., & Djordjevic, J.T. (2006), Lipid rafts in Cryptococcus neoformans concentrate the virulence determinants phospholipase B1 and Cu/Zn superoxide dismutase. Eukaryotic Cell, 5(3), 488-498 [PMID: 16524904]