New data-driven mathematical models of collective cell motion. Cancer and chronic wounds are a national, and indeed, international health problem set to worsen as our population ages. Predictive and interpretive tools are required to improve our understanding of collective cell migration in relation to cancer and chronic wounds. This project will produce new validated mathematical tools for predicting collective cell migration in a general framework that can deal with application-specific detail ....New data-driven mathematical models of collective cell motion. Cancer and chronic wounds are a national, and indeed, international health problem set to worsen as our population ages. Predictive and interpretive tools are required to improve our understanding of collective cell migration in relation to cancer and chronic wounds. This project will produce new validated mathematical tools for predicting collective cell migration in a general framework that can deal with application-specific details, such as the role of cell shape and cell size. Although cell shape and size are known to affect collective cell migration, standard mathematical models ignore these details. This project will produce new predictive mathematical modelling tools that are validated by new experimental data. Read moreRead less
mTOR signalling in serous ovarian cancer. Serous ovarian cancer is the most aggressive and lethal gynaecological cancer in Australian women. Activation of Mammalian Target of Rapamycin (mTOR) is frequently observed and associated with poor prognosis in ovarian cancer patients. However, the mechanisms dysregulating mTOR in the pathogenesis of ovarian cancer are unknown. In preliminary studies, deletion of genes regulating mTOR signalling in up to 60 per cent of human serous ovarian cancer patien ....mTOR signalling in serous ovarian cancer. Serous ovarian cancer is the most aggressive and lethal gynaecological cancer in Australian women. Activation of Mammalian Target of Rapamycin (mTOR) is frequently observed and associated with poor prognosis in ovarian cancer patients. However, the mechanisms dysregulating mTOR in the pathogenesis of ovarian cancer are unknown. In preliminary studies, deletion of genes regulating mTOR signalling in up to 60 per cent of human serous ovarian cancer patients was observed. This project will provide mechanistic details of involvement of mTOR signalling in pathogenesis of the serous ovarian carcinoma, and develop a rationale for targeting mTOR pathway in these patients. Read moreRead less
Studying precancerous stem cells that cause T cell leukaemia. Recent research has identified abnormal stem cells that are the cause of T cell leukaemia. They are also resistant to therapeutics suggesting that they could be a cause of relapse. The aim of this project is to determine the abnormal pathways that cause these cells to become immortal and to determine new therapeutic strategies to eliminate them.
Identification of novel therapeutic targets for selectively eliminating cancer stem cells in paediatric leukaemia. Leukaemia is the most common form of cancer in children, and while the majority of children can be cured, those who relapse face a dire prognosis. It is widely believed that leukemic stem cells are responsible for relapse and this project will aim to unravel their underlying biology and identify new targets for therapeutic approaches to the disease.
Studies in cancer control. As life expectancy in Australia (and throughout the world) continues to rise, so will the burden of cancer escalate. Treating cancer after diagnosis is costly, and in many instances, unsuccessful. Preventive strategies promise to reduce the future cancer burden, yet our knowledge in this arena is limited by the lack of credible research as to what works and what does not. This application addresses this gap directly by conducting research into the control of two cancer ....Studies in cancer control. As life expectancy in Australia (and throughout the world) continues to rise, so will the burden of cancer escalate. Treating cancer after diagnosis is costly, and in many instances, unsuccessful. Preventive strategies promise to reduce the future cancer burden, yet our knowledge in this arena is limited by the lack of credible research as to what works and what does not. This application addresses this gap directly by conducting research into the control of two cancers which exact a growing toll in Australia and elsewhere. The work seeks to identify and understand the causal pathways to cancer, and then use this information to devise evidence-based strategies for cancer control.Read moreRead less
Molecular hallmarks of androgen receptor targeting in prostate cancer. There is a critical need in oncology drug development for better biomarkers of response to prostate cancer therapies, clinically to assist with treatment decision making, and pre-clinically to facilitate translation of emerging agents into clinical practice. Using a unique explant culture model, this project will identify protein and lipid markers that can be used to accurately and reliably assess response to androgen recepto ....Molecular hallmarks of androgen receptor targeting in prostate cancer. There is a critical need in oncology drug development for better biomarkers of response to prostate cancer therapies, clinically to assist with treatment decision making, and pre-clinically to facilitate translation of emerging agents into clinical practice. Using a unique explant culture model, this project will identify protein and lipid markers that can be used to accurately and reliably assess response to androgen receptor (AR)-targeting therapies in human prostate tumours. The identification and functional assessment of these biomarkers will identify those that can be used as surrogate endpoints in clinical trials, facilitate earlier approval of investigational agents and lead to improved options for therapeutic management of prostate cancer.Read moreRead less
The critical role of the class III histone deacetylase SIRT2 in stabilizing N-Myc oncoprotein. Cancer is the commonest cause of death from disease in children. Neuroblastoma is the commonest solid tumor in early childhood. This project will investigate the critical roles of SIRT2 protein in increasing the expression of N-Myc oncoprotein and consequently inducing neuroblastoma, and SIRT2 inhibitors as anticancer agents.
The role of human single-stranded binding protein (hSSB1) in DNA damage repair and tumorogenesis. Cancer is a leading cause of disease related death world wide, accounting for over 13% of all deaths in 2007. Approximately 38,000 people died in Australia from cancer in 2005. Cancer results from a single cell losing a vital part of its genetic information, this results in the cell losing its normal programming and initiates a process of rapid growth and multiplication. This research project aims t ....The role of human single-stranded binding protein (hSSB1) in DNA damage repair and tumorogenesis. Cancer is a leading cause of disease related death world wide, accounting for over 13% of all deaths in 2007. Approximately 38,000 people died in Australia from cancer in 2005. Cancer results from a single cell losing a vital part of its genetic information, this results in the cell losing its normal programming and initiates a process of rapid growth and multiplication. This research project aims to look at the mechanisms that exist to prevent this initial loss of genetic material within an individual cell. It further aims to translate theses discoveries into the clinic, providing new tools for diagnosis and prognosis of specific cancers and to establish links with major pharmaceutical companies to develop novel anticancer therapies.Read moreRead less
Crosstalk between breast cancer cells and the microenvironment to promote metastasis. Breast cancer spread (metastasis) to distant tissues is usually fatal. It is now clear that cross-talk between cancer cells and other normal cells is essential for metastasis and previous studies have discovered two key mechanisms: tumour cell suppression of immune defence pathways to escape immune recognition, and activation of proteases to promote invasion and blood vessel growth. Using unique models and cell ....Crosstalk between breast cancer cells and the microenvironment to promote metastasis. Breast cancer spread (metastasis) to distant tissues is usually fatal. It is now clear that cross-talk between cancer cells and other normal cells is essential for metastasis and previous studies have discovered two key mechanisms: tumour cell suppression of immune defence pathways to escape immune recognition, and activation of proteases to promote invasion and blood vessel growth. Using unique models and cellular imaging, this project aims to investigate the cell specific functions of these pathways and the therapeutic potential of altering their expression and function. This project may lead to the development of novel predictors of metastasis in patients and new targeted therapeutics to prevent breast cancer spread.Read moreRead less
Controlling apoptotic cell death in health and disease. Regulating how and when cells die is crucial for the development and maintenance of a healthy body and mind. This project will investigate the proteins that are responsible for controlling cell death with the view to identifying novel ways to target these proteins for the treatment of disorders such as cancer, neurodegenerative disease and autoimmunity.