Dr Traude Beilharz
Tel: +61-3-9902 9183
Fax: +61-3-9905 3726
Office: Room 255, Level 2, Building 76
Reception: Building 77, Science Technology Research & Innovation Precinct
My lab asks how cells regulate the birth, life and death of RNA molecules using Next Generation Sequencing (NGS).
We are experiencing a major re-think in cell biology. Up until very recently, the major focus in gene-regulation was on DNA and DNA-binding proteins. However, it turns out that RNA is not just a passive intermediary between DNA and proteins; RNA also has structural and regulatory functions in addition to its coding functions. Therefore, we are interested in how both coding and non-coding RNA is expressed and regulated in cells, and how the fine-tuning of this expression, which differentiates health from disease, is maintained.
NGS provides a holistic, systems level view of the RNA expression profile in cells, and since disease often leaves signature fingerprints of deregulation on such profiles, NGS can be a powerful diagnostic for various disease states including for cancer. My lab uses custom RNA-seq technologies in a diverse set of model organism and cultured-cells to study RNA dynamics. Specifically, we are interested in the post-transcriptional regulation of RNA that determines when, where and how often, mRNA is translated to make proteins. Because we seek to understand how every RNA in our system is regulated, our experiments often have 100s of millions of data-points and thus require the input of computational biologists.
PAT-seq: A high throughput approach to measuring RNA dynamics. We developed PAT-seq (for Poly(A)-Tail sequencing) to measure genome-wide RNA concentration, the position of polyadenylation and polyadenylation-length in eukaryotic cells. This approach together with a new bioinformatic data analysis pipeline makes hundreds of millions of individual data-points available to biologists.
Currently funded projects
- Nocturnin: A post-transcriptional regulator of circadian fat metabolism:
Metabolism is tightly coupled to the circadian rhythm. For example, we use fat in the morning and stored it in the evening. This project seeks to define the mRNA targets of the circadian deadenylase Nocturnin, that require silencing at the start of the day for the normal fat deposition.
- The 3'UTR Codes that control mRNA translation in development:
We apply purpose-built RNA-seq technologies and targeted animal models to dissect the functional codes of regulated protein translation. miRNA binding sites in the 3'UTR of mRNA are one such code, but the control of translation is more complex than just these. There are also codes to localise translation, to signal activation of translation; and the codes themselves can be lost or gained by a change in the site of cleavage and adenylation during mRNA maturation.
(Students interested in careers in computational biology are encouraged to make contact)
Research Assistant: Mr Roy Lee
PhD Student: Ms Angavai Swaminathan
Honours Students: Ms Anu George and Mr Kirill Tsyganov
Dr Paul Harrison (Victorian Bioinformatics Consortium and Life Science Computation Centre)
Dr David Powell (Victorian Bioinformatics Consortium and Life Science Computation Centre)
Collaborations in 3'UTR dynamics
Prof. Anita Corbett: (Emory University School of Medicine: USA).
Assistant Prof. John Kim: (Life Sciences Institute: ANN Arbour; USA).
Assoc. Prof. Robin Anderson: (Peter MacCallum Cancer Centre).
Dr Julian Heng: (Australian Regenerative Medicine Institute; Monash).
Dr Jose Polo: (Developmental Biology; Monash).
Dr Ana Traven: (Department of Biochemistry and Molecular Biology; Monash).
Dr Peter Boag: (Department of Biochemistry and Molecular Biology; Monash).
Prof. Thomas Preiss: (The John Curtin School of Medicine; ANU).
Prof. Mark Sleeman: (Department of Biochemistry and Molecular Biology; Monash).
Selected recent publications
- Hewitt VL, Heinz E, Shingu-Vazquez M, Qu Y, Jelicic B, Lo TL, Beilharz TH, Dumsday G, Gabriel K, Traven A, and Lithgow T. (2012) A model system for mitochondrial biogenesis reveals evolutionary rewiring of protein import and membrane assembly pathways. Proc Natl Acad Sci U S A 109(49):E3358-3366
- Uwamahoro N, QuY, Jelicic B, Lo TL, Beaurepaire C, Bantun F, Quenault T, Boag PR, Ramm G, Callaghan J, Beilharz TH, Nantel A, Peleg AY, and Traven, A. (2012). Functions of the Mediator subunit Med31 in Candida albicans support a role in shaping species-specific gene expression: PLoS genetics 8(4):e1002613.
- Traven A, Jänicke, A., Harrison P, Swaminathan A, Seemann T, and Beilharz TH. (2012) Transcriptional profiling of a yeast colony provides new insight into the heterogeneity of multicellular fungal communities. PloS one 7(9):e46243.
- Sengupta MS, Low WY, Patterson JR, Kim HM, Traven A, Beilharz TH, Colaiacovo MP, Schisa JA, and Boag, P. R.. (2012) ifet-1 is a broad scale translational repressor required for normal P granule formation in C. elegans. J cell sci. [Epub ahead of print]
- Qu Y, Jelicic B, Pettolino F, Perr A, Lo TL, Hewitt VL, Bantun F, Beilharz TH, Peleg, AY, Lithgow T, Djordjevic JT, and 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 11(4):532-544.
- Jänicke A, Vancuylenberg J, Boag PR, Traven A, and Beilharz TH (2012). ePAT: a simple method to tag adenylated RNA to measure poly(A)-tail length and other 3' RACE applications: RNA 18(6):1289-1295
- Lo TL, Qu Y, Uwamahoro N, Quenault T, Beilharz TH, and Traven A (2012). The mRNA Decay Pathway Regulates Expression of the Flo11 Adhesin and Biofilm Formation in Saccharomyces cerevisiae. Genetics. 191: 1387-91
- 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 post-transcriptional regulator Ccr4-Pop2. Molecular Microbiology 79: 968-989
- Clancy JL, Wei GH, Echner N, Humphreys DT, Beilharz TH, Preiss T (2011). mRNA isoform diversity can obscure detection of miRNA-mediated control of translation. RNA 17: 1025-1031
- Traven A, Beilharz TH, Lo TL, Lueder F, Preiss T, and Heierhorst J. (2009) The Ccr4-Pop2-NOT mRNA Deadenylase contributes to Septin Organization in Saccharomyces cerevisiae. Genetics. 182, 955-966