To investigate the role of the protein kinase SMG-1 in the stress response. This project is included in the designated priority area of research Promoting and Maintaining Good Health and Ageing Well. It represents a mouse model to assist in the study of human disease. It is the first mouse model for SMG-1, a protein kinase that protects against a variety of different forms of stress. The strength of the model is that it can be combined with other mouse models to interrogate and elucidate the eve ....To investigate the role of the protein kinase SMG-1 in the stress response. This project is included in the designated priority area of research Promoting and Maintaining Good Health and Ageing Well. It represents a mouse model to assist in the study of human disease. It is the first mouse model for SMG-1, a protein kinase that protects against a variety of different forms of stress. The strength of the model is that it can be combined with other mouse models to interrogate and elucidate the events occurring in different pathways for stress. The expectation is that ground-breaking data will be generated with this model providing scientific leadership on the role of this protein. It will also assist in establishing new collaborations.Read moreRead less
DNA methylation-based diagnosis of cancer and identification of novel therapeutic targets. In our aging society, cancer represents a severe economic and quality-of-life threat. DNA methylation switches genes off, and recently, it was shown that defects in DNA methylation contribute to human diseases including cancer. This project will identify defects in DNA methylation associated with cancer. Identifying these defects will enable us to design non-invasive, early diagnostic tests for cancer on b ....DNA methylation-based diagnosis of cancer and identification of novel therapeutic targets. In our aging society, cancer represents a severe economic and quality-of-life threat. DNA methylation switches genes off, and recently, it was shown that defects in DNA methylation contribute to human diseases including cancer. This project will identify defects in DNA methylation associated with cancer. Identifying these defects will enable us to design non-invasive, early diagnostic tests for cancer on blood or bodily excretions, and to pursue novel therapeutic approaches for treating cancer. The expected outcomes would generate exports to markets in the USA and Europe and replace imports of drugs and technology to treat cancer.Read moreRead less
Characterisation of APC intracellular trafficking pathways. This is a fundamental research project aimed at addressing the cell biology of the APC tumour suppressor protein. APC gene mutations are directly linked to the development of colorectal cancer, a serious healthcare issue in Australia with approximately 12,400 new cases diagnosed each year and around 4,700 deaths. The severity of cases in men and women who develop colorectal cancer makes this a socio-economically serious health issue, an ....Characterisation of APC intracellular trafficking pathways. This is a fundamental research project aimed at addressing the cell biology of the APC tumour suppressor protein. APC gene mutations are directly linked to the development of colorectal cancer, a serious healthcare issue in Australia with approximately 12,400 new cases diagnosed each year and around 4,700 deaths. The severity of cases in men and women who develop colorectal cancer makes this a socio-economically serious health issue, and our project falls within the Research Priority 2: Promoting and Maintaining Good Health. If successful our project will identify localisation patterns and pathways of movement of APC within cells, which could ultimately help in development of treatments. Read moreRead less
Mouse models for the identification of factors involved in muscle adaptation. The ability of muscle to adapt to meet functional demands is essential for mobility in normal daily life, in ageing well, in individuals with muscle diseases and nerve damage and in athletes. The ability of muscle to change its cellular composition is desirable for the livestock industry. Knowledge of how genes in muscle cells are regulated to adapt to demands has significant implications for public health and economic ....Mouse models for the identification of factors involved in muscle adaptation. The ability of muscle to adapt to meet functional demands is essential for mobility in normal daily life, in ageing well, in individuals with muscle diseases and nerve damage and in athletes. The ability of muscle to change its cellular composition is desirable for the livestock industry. Knowledge of how genes in muscle cells are regulated to adapt to demands has significant implications for public health and economic benefits. We have devised model systems that will allow us to identify the regulators of these genes in order to develop therapies to combat these changes in ageing and damaged muscle, to improve the quality of meat and optimise sport performance.Read moreRead less
A novel role for SMG-1 protein kinase in stress granule formation and the stress response. Humans are constantly exposed to agents in the environment that threaten the integrity of their cells and increases the risk of cancer and other pathologies. Cells have developed repair mechanisms to cope with damage to their DNA and avoid long term effects. The emphasis in this application is to investigate the mechanisms by which stress affects the transcriptional machinery in the cell. A description of ....A novel role for SMG-1 protein kinase in stress granule formation and the stress response. Humans are constantly exposed to agents in the environment that threaten the integrity of their cells and increases the risk of cancer and other pathologies. Cells have developed repair mechanisms to cope with damage to their DNA and avoid long term effects. The emphasis in this application is to investigate the mechanisms by which stress affects the transcriptional machinery in the cell. A description of the processes involved will assist in understanding how specific disease states arise and will provide a means of devising compounds/drugs to assist the response to stress. Read moreRead less
The molecular role of ADAM12 in maintenance of skeletal muscle, myogenesis and adipogenesis. An understanding of the molecular control of skeletal muscle growth, maintenance and balance between muscle and fat production is of fundamental importance for a competitive meat industry, for the promotion of strong muscles in the ageing population and for disorders such as muscle diseases, diabetes and obesity. This project will enhance strong international collaborations and expand cutting-edge resear ....The molecular role of ADAM12 in maintenance of skeletal muscle, myogenesis and adipogenesis. An understanding of the molecular control of skeletal muscle growth, maintenance and balance between muscle and fat production is of fundamental importance for a competitive meat industry, for the promotion of strong muscles in the ageing population and for disorders such as muscle diseases, diabetes and obesity. This project will enhance strong international collaborations and expand cutting-edge research within Australia with many potential economic benefits for the meat industry, biotechnology and health. The expertise developed by this pioneering research will ensure that Australia is well placed to harness new technologies and exploit future advances in this fast-moving field of muscle biology.Read moreRead less
Do pancreatic stellate cells play a role in pancreatic exocrine secretion? 3 major national benefits: 1)Alignment with research priority goals of preventative health care and ageing well ageing productively. Elucidation of mechanisms of action of CCK and the interaction of PSCs and acinar cells in mediating pancreatic secretion will help refine our approach to the prevention and treatment of disorders related to the above processes viz. maldigestion, malabsorption, obesity and pancreatic cancer. ....Do pancreatic stellate cells play a role in pancreatic exocrine secretion? 3 major national benefits: 1)Alignment with research priority goals of preventative health care and ageing well ageing productively. Elucidation of mechanisms of action of CCK and the interaction of PSCs and acinar cells in mediating pancreatic secretion will help refine our approach to the prevention and treatment of disorders related to the above processes viz. maldigestion, malabsorption, obesity and pancreatic cancer. 2)Enhancement of Australia's reputation in gastrointestinal (GI) research through a unique collaboration between internationally recognised researchers in GI and pancreatic biology. 3)Training opportunities for Australian research students and scientists in physiology, gastroenterology and pancreatology.Read moreRead less
Role of autophagy in degradation of endoplasmic reticulum (ER)-localised protein aggregates. This study will provide a new understanding of protein aggregate accumulation in the endoplasmic reticulum (ER), a phenomenon that occurs in aging cells and protein conformational diseases, and under stress conditions and during secretory protein overexpression. This information will inform strategies to prevent the onset of protein conformational diseases and help identify targets for pharmaceutical int ....Role of autophagy in degradation of endoplasmic reticulum (ER)-localised protein aggregates. This study will provide a new understanding of protein aggregate accumulation in the endoplasmic reticulum (ER), a phenomenon that occurs in aging cells and protein conformational diseases, and under stress conditions and during secretory protein overexpression. This information will inform strategies to prevent the onset of protein conformational diseases and help identify targets for pharmaceutical intervention. In addition, a powerful model system for studies of ER protein aggregation will be established, high-level training in biochemistry and morphometry will be provided, and an international collaboration of the highest calibre will be initiated.Read moreRead less
Assessing gene function in the developing brain using zebrafish as a model system. As the average life expectancy in western countries increases there is an increasing incidence of mental health problems in the general population. Therapeutic approaches to Alzhemier's and Parkinson's disease as well as to brain injury arising from stroke rely on a thorough understanding of the molecular and physiological mechanisms of normal growth of this tissue. These are the very processes that need to be rea ....Assessing gene function in the developing brain using zebrafish as a model system. As the average life expectancy in western countries increases there is an increasing incidence of mental health problems in the general population. Therapeutic approaches to Alzhemier's and Parkinson's disease as well as to brain injury arising from stroke rely on a thorough understanding of the molecular and physiological mechanisms of normal growth of this tissue. These are the very processes that need to be reactivated in these diseases for recovery of function. This project seeks to understand normal development of the brain and in doing so it will expose novel targets for therapy in the aged. Read moreRead less
Surface engineering of biomaterials for optimal bone bonding characteristics. The ideal bone-implant material is hydroxyapatite. Chemically similar to bone mineral, hydroxyapatite is capable of inducing bone ongrowth. An ideal surface coating for metal hip implants, plasma spraying has been the preferred commercial hydroxyapatite coating technique. Until recently, it was always presumed that the bioactivity of hydroxyapatite resulted from its surface chemistry. However, a recent study has shown ....Surface engineering of biomaterials for optimal bone bonding characteristics. The ideal bone-implant material is hydroxyapatite. Chemically similar to bone mineral, hydroxyapatite is capable of inducing bone ongrowth. An ideal surface coating for metal hip implants, plasma spraying has been the preferred commercial hydroxyapatite coating technique. Until recently, it was always presumed that the bioactivity of hydroxyapatite resulted from its surface chemistry. However, a recent study has shown that the bioactivity of HAp coatings strongly correlates with surface roughness on the scale of bone cells. This project will explore cell-attachment behaviour for hydroxyapatite coatings prepared by plasma spraying compared with engineered surface morphology/chemistry by microlithography and vapour coating.Read moreRead less