Projects available for Honours and PhD |
- Our research involves developing models using Drosophila to understand the initiation and progression of human diseases, including cancer and neurodegeneration.
- The cancer studies (Projects 1-5) focus on genes called oncogenes and tumour suppressor genes, which are required for tight regulation of the cell cycle.
- For the neurodegenerative studies (Project 6) we have developed Drosophila models to investigate how proteins such as Huntington can aggregate in cells to disrupt neural functioning.
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Project 1 - Novel regulators of Wingless, dmyc and cell cycle
Loss of cell cycle control is a fundamental first step in cancer initiation. Crooked legs (Crol) drives cell cycle progression and wing imaginal disc overgrowth (shown right), by leading to the upregulation of critical cell cycle genes. Crol is an important upstream regulator of the Wingless (Wg) signalling pathway. Future research is aimed towards determining how Crol regulates cell cycle progression via wg transcription.
*Project 2 - To determine how Hfp regulates dmyc
Myc drives cells to overgrow (see figure below) and as a consequence is a potent oncogene. Our work has shown that Hfp controls dmyc transcription and overgrowth via the DNA helicase, Haywire. Future research projects are aimed towards determining 1) how specific Haywire alleles abrogate Hfp-mediated dmyc repression and growth and 2) the signalling pathways upstream of Hfp and Hay that control dmyc transcription.
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*Project 3 - Drosophila models for ribosome biogenesis and growth
Up-regulation of ribosome biogenesis can lead to the uncontrolled proliferation and contribute directly to cancer. We aim to use Drosophila as a model to 1) determine how mitogenic signaling pathways including c-MYC modulate rRNA gene transcription and cell growth; 2) to determine the contribution of rRNA gene silencing to DNA recombination and genomic instability and 3) to investigate the mechanism by which ribosomal proteins can behave as tumour suppressor genes.
*These projects are a collaboration with Assoc. Prof. Ross Hannan at the Peter MacCallum Cancer Centre; http://www.petermac.org/Research/GrowthControl
**Project 4 - The role of retinoblastoma in stem cell differentiation
Stem cells are essential for tissue growth and maintenance throughout the lifetime of an organism. Conserved molecular signals from the local tissue environment are necessary for regulating stem cell divisions. Disruption to these signals can result in cancerous-like cell overgrowth. We have identified a novel pathway for the tumour suppressor protein Retinoblastoma in stem cell differentiation. This project will aim to examine the role of Retinoblastoma in regulating stem cell development by identifying transcriptional targets as well as the molecular signals involved. |
**Project 5 - Myc regulation in stem cells
Recent studies on cancer stem cells (CSCs) have emphasized the importance of the interactions between stem cells and their microenvironment or "niche". We aim to use Drosophila stem cell models to identify the signals from the niche required to control levels of the Myc oncogene in the germline stem cells, which is important to prevent the formation of germline tumours (shown right). |
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**These projects are a collaboration with 1) Dr Greg Somers, La Trobe Institute for Molecular Science (LIMS); http://www.latrobe.edu.au/genetics/staff/GSomers/index.html and 2) Dr Gary Hime, Department Anatomy and Cell Biology, University Melbourne; http://www.anatomy.unimelb.edu.au/researchlabs/hime/index.html |
***Project 6 - Drosophila models for neurodegenerative disease
Proteins such as Huntington can misfold and aggregate in cells to disrupt normal cellular functioning, which is intimately associated with neurodegenerative disease. We have developed Drosophila models for Huntington’s disease in order to determine how defects in protein conformation affect neural functioning. This project aims to determine the physiological mechanisms underpinning Huntington’s disease in vivo using the Drosophila brain (shown below).
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