Dr Ana Traven
Tel: +61-3-9902 9219
Fax: +61-3-9905 3726
Rm 251, Level 2, Building 76 (STRIP 2)
MOLECULAR MECHANISMS OF FUNGAL PATHOGENESIS
Wild type C. albicans
biofilms imaged with Scanning
electron microscopy (SEM)
The worm C. elegans is an
effective model host for C. albicans
infections. C. albicans forms long
filamentous cells upon infection,
piercing through the cuticle of the worm
and causing death. We are using this model
infection system to screen for new regulators
of C. albicans virulence.
The work in my lab is focused on Candida albicans, the main pathogenic fungus causing disease in humans. C. albicans is an opportunistic pathogen which can cause life-threatening disease in the most vulnerable patients, for example people in intensive care units and cancer patients. Mortality rates for systemic disease are high, commonly >30%. New strategies for treatment and prevention are urgently needed.
The projects in my lab aim to understand key pathways important for virulence of C. albicans: the synthesis of the cell wall, and changes to fungal cell morphology and growth which enable formation of multicellular, drug resistant biofilms. We are using an interdisciplinary approach to these questions, combining Molecular genetics of C. albicans, with Biochemistry, Glycomics, Lipidomics, Transcriptomics, Confocal and Electron microscopy imaging, as well as Virulence studies in animal models of infection. Our C. albicans work is also informed by studies in the model yeast Saccharomyces cerevisiae, which represents an unparalleled genetic model for eukaryotic biology. We are using these two yeasts comparatively to understand the system networks that impinge on cell wall integrity and changes to cell morphology, and ultimately control virulence of C. albicans towards humans.
The current projects in the lab are:
- Understanding how mitochondrial function impacts on cell wall integrity, virulence, and antifungal drug susceptibility in C. albicans.
- Characterisation of gene expression regulators controlling hyphal growth and biofilm formation in C. albicans.
- Understanding the regulation of posttranscriptional networks by RNA binding proteins in model and pathogenic yeasts, and how they impact on developmental transitions.
Dr. Yue Qu (postdoc)
Dr. Jiyoti Verma-Gaur (postdoc)
Ms Nathalie Uwamahoro (PhD student)
Ms Tara Quenault (PhD student)
Ms Tricia Lo (Research Assistant)
Dr. Michael Dagley (postdoc 2009-2010)
Dr. Branka Jelicic (postdoc 2011-2012; European Group of Eight Fellow)
A recent lab photo: Back: Tara Quenault and Nathalie Uwamahoro; Front: Tricia Lo, Ana Traven and Yue Qu.
Regulation of gene expression in pathogenic and model yeasts
- Uwamahoro N, Qu Y, Jelicic N, Lo TL, Beaurepaire C, Bantun F, Quenault T, Boag PR, Ramm G, Callaghan J, Beilharz TH, Nantel A, Peleg AY & TRAVEN A (2012) The functions of Mediator in Candida albicans support a role in shaping species-specific gene expression. PLoS Genet 8 (4): e1002613
- Lo TL, Qu Y, Uwamahoro N, Quenault T, Beilharz TH & TRAVEN A (2012) The mRNA decay pathway regulates expression of the Flo11 adhesin and biofilm formation in Saccharomyces cerevisiae. Genetics 191: 1387
- TRAVEN A#, Jänicke A, Harrison P, Swaminathan A, Seemann T & Beilharz TH# (2012) Transcriptional profiling of a yeast colony provides new insight into the heterogeneity of multicellular fungal communities. PLoS One 7:e46243. # equal senior author
- Quenault T, Lithgow T, TRAVEN A (2011) PUF proteins: repression, activation and mRNA localization. Trends Cell Biol. 21(2): 104-12.
- TRAVEN A, Lo TL, Lithgow T, Heierhorst J (2010) The yeast PUF protein Puf5 has Pop2-independent roles in response to DNA replication stress. PLoS One 5(5):e10651.
- TRAVEN A, Beilharz TH, Lo TL, Lueder F, Preiss T, Heierhorst J (2009) The Ccr4-Pop2-NOT mRNA deadenylase contributes to septin organization in Saccharomyces cerevisiae. Genetics. 182(4): 955-66.
- TRAVEN A, Jelicic B, Sopta M (2006) Yeast Gal4: a transcriptional paradigm revisited. EMBO Rep. 7(5): 496-9.
The mitochondria-cell wall functional network in C. albicans
- Hewitt VL, Heinz E, Shingu-Vazquez M, Qu Y, Jelicic B, Lo TL, Beilharz TH, Dumsday G, Gabriel K, TRAVEN A#, Lithgow T#. A model system for mitochondrial biogenesis reveals evolutionary rewiring of protein import and membrane assembly pathways. Proc Natl Acad Sci U S A. In press; E Pub November 14th. # equal senior author
- Qu Y, Jelicic B, Pettolino F, Perry A, Lo TL, Hewitt VL, Bantun F, Beilharz TH, Peleg AY, Lithgow T, Djordjevic J & TRAVEN A (2012) Studies of the mitochondrial Sorting and Assembly Machinery subunit Sam37 in Candida albicans: insight into the roles of mitochondria in fitness, cell wall integrity and virulence. Eukaryot Cell 4: 532
- Shingu-Vazquez M and TRAVEN A (2011) Mitochondria and fungal pathogenesis: drug tolerance, virulence and potential for antifungal therapy. Eukaryot Cell 10: 1376
- Dagley MJ, Gentle IE, Beilharz TH, Pettolino FA, Djordjevic JT, Lo TL, Uwamahoro N, Rupasinghe T, Tull DL, McConville M, Beaurepaire C, Nantel A, Lithgow T, Mitchell AP, TRAVEN A (2011) Cell wall integrity is linked to mitochondria and phospholipid homeostasis in Candida albicans through the activity of the posttranscriptional regulator Ccr4-Pop2. Mol Microbiol. 79(4): 968-89.
- TRAVEN A, Wong JM, Xu D, Sopta M, Ingles CJ (2001) Interorganellar communication. Altered nuclear gene expression profiles in a yeast mitochondrial DNA mutant. J Biol Chem. 276(6): 4020-7.