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
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
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
MOLECULAR APPROACHES TO OVERCOME SCABIES AND ASSOCIATED DISEASE. Scabies causes childhood pyoderma predisposing to severe disease in later life. It is a major increasing health burden in Indigenous people of Northern Australia. Drug resistance is developing in mites and bacteria. The lack of clinical material has hampered molecular research and this work will use comparative genomics of parasitic and free living mites and microbiome analysis to understand fundamental aspects of mite biology and ....MOLECULAR APPROACHES TO OVERCOME SCABIES AND ASSOCIATED DISEASE. Scabies causes childhood pyoderma predisposing to severe disease in later life. It is a major increasing health burden in Indigenous people of Northern Australia. Drug resistance is developing in mites and bacteria. The lack of clinical material has hampered molecular research and this work will use comparative genomics of parasitic and free living mites and microbiome analysis to understand fundamental aspects of mite biology and pathogenesis. The understanding of proteins that are essential for mite survival and interfere with host defences will allow the informed design of peptide inhibitors as a new strategy to develop alternative treatment options.Read moreRead less
Using mouse genetics to understand skin development and cell biology. During embryonic development the skin forms a protective barrier which permits life outside the womb and provides a window into the biology of cells. This project aims to use the skin to identify and characterise genes necessary for embryonic development and maintenance, the development of diseases and to explore their broader roles in other organs.
Designed peptides as functional surfactants. Surfactants are essential in many applications for making oil-water mixtures, e.g. in dissolving drugs, extracting crude oil or spraying crops. However, chemical surfactants are toxic and can accumulate in the environment. This work will develop biodegradable surfactants that can be switched "on" and "off" as needed and do not cause toxicity to living organisms. One of many potential applications is in vaccines for use in remote Aboriginal communities ....Designed peptides as functional surfactants. Surfactants are essential in many applications for making oil-water mixtures, e.g. in dissolving drugs, extracting crude oil or spraying crops. However, chemical surfactants are toxic and can accumulate in the environment. This work will develop biodegradable surfactants that can be switched "on" and "off" as needed and do not cause toxicity to living organisms. One of many potential applications is in vaccines for use in remote Aboriginal communities. In these communities, skin infections from scabies and streptococcus are epidemic, and can lead to kidney failure and heart disease. A non-damaging skin cream based on the peptides could both treat short-term discomfort and deliver a vaccine to prevent long-term health consequences.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.
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.
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
Understanding endocrine tumorigenesis - opportunities for new diagnostics and therapies. This project will generate new knowledge significant for improving cancer diagnosis and designing new therapies for cancer patients as we embrace the personalised medicine era. Specific focus is on endocrine tumours. This research has as its aim improved survival for people diagnosed with cancer.