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
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
Modelling cell invasion incorporating the epithelial to mesenchymal transition: Exploring therapies to control wound healing and cancer progression. Cancer and wounds are closely related, commonly lethal, diseases. Both require cell growth and invasion. This project will apply experimental measurements to create new mathematical models of cancer and wounds; models that will inform new targets and strategies for the treatment of these deadly diseases.
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.
A new hierarchy of mathematical models to quantify the role of ghrelin during cell invasion. Ghrelin is a recently-discovered growth factor that regulates appetite and promotes tumour growth by enhancing cell invasion. The mechanisms by which ghrelin enhances cell invasion are, at present, unknown. This innovative project will develop a new hierarchy of multiscale mathematical models that will be used to quantify how ghrelin modulates cell behaviour (motility, proliferation and death) and provid ....A new hierarchy of mathematical models to quantify the role of ghrelin during cell invasion. Ghrelin is a recently-discovered growth factor that regulates appetite and promotes tumour growth by enhancing cell invasion. The mechanisms by which ghrelin enhances cell invasion are, at present, unknown. This innovative project will develop a new hierarchy of multiscale mathematical models that will be used to quantify how ghrelin modulates cell behaviour (motility, proliferation and death) and provide insight into the precise details of how ghrelin promotes cell invasion. This project will demonstrate the potential for ghrelin-based strategies to control cell invasion. By linking appetite regulation and tumour growth, the outcomes from this project will inform Australian health policy in this important area.Read moreRead less
Information theoretic approaches to optimise genome wide association studies with application to continuous and discrete traits. This project aims to develop new mathematical methods to find genetic associations from new genome-wide studies of colorectal cancer and breast cancer risk factors. If successful, this will result in improved use of expensive genetic data to better predict and understand diseases, conditions and other characteristics for humans, animals and plants.
Engineered Hydroxamic Acids for Zirconium-89 Positron Emission Tomography (PET) Imaging of Prostate Cancer. Positron emission tomography (PET) using a zirconium-89-ligand complex bound to a prostate-specific membrane antigen is used to detect and monitor prostate cancer. The hydroxamic acid-based ligand bound to zirconium has a high affinity towards iron, which can cause metal exchange in vivo and loss of radiotracer. The project will prepare new ligands with a higher specificity towards zirconi ....Engineered Hydroxamic Acids for Zirconium-89 Positron Emission Tomography (PET) Imaging of Prostate Cancer. Positron emission tomography (PET) using a zirconium-89-ligand complex bound to a prostate-specific membrane antigen is used to detect and monitor prostate cancer. The hydroxamic acid-based ligand bound to zirconium has a high affinity towards iron, which can cause metal exchange in vivo and loss of radiotracer. The project will prepare new ligands with a higher specificity towards zirconium over iron, and measure immuno-PET imaging activity. A second series of macrocyclic zirconium-specific ligands will be prepared to establish the relationship between variable water-lipid solubility and pharmacokinetic properties. The results will increase the capability of immuno-PET for prostate cancer detection and improve survival outcomes.Read moreRead less
Linking chemical synthesis with protein discovery to reveal key biological pathways. The project aims to pioneer a chemical biology technology to deliver a much better understanding of key molecules that regulate diseases such as cancer. For decades phorbol esters have been prominent molecules for controlling cell switches in complex diseases but our knowledge is incomplete because of the limited natural abundance of these molecules.
Targeting mitochondria with mitocans to treat cancer: mechanistic aspects. Mitochondria are the power-house of the cell and also the reservoir of proteins causing the demise of cancer cells, therefore suppressing tumour progression. This project proposes a novel way to modify certain compounds, increasing their level in mitochondria in order to maximise their anti-cancer effect.
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.