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
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
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
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
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
Oxidative Damage and Cell Ageing. This research will benefit Australia by providing a fundamental understanding of how cells age. This will have immediate international impact at the scientific level and will inform strategies to reduce the rate of ageing and alleviation of age-related disorders. In the longer term the research may provide commercial and social outcomes by identifying antioxidant systems that will provide a genuine benefit in reducing ageing.
Cellular Responses to Oxidative Damage: Cell Aging. The aim of this project is to identify the mechanisms by which oxidative stress and free radical damage cause cell aging. This work will make a significant contribution to our understanding of the aging process in cells by identifying the major reactive oxygen species that contribute to cell aging, which defence systems and antioxidants provide the greatest degree of protection, what damage accumulates as cells age and which genetic systems ar ....Cellular Responses to Oxidative Damage: Cell Aging. The aim of this project is to identify the mechanisms by which oxidative stress and free radical damage cause cell aging. This work will make a significant contribution to our understanding of the aging process in cells by identifying the major reactive oxygen species that contribute to cell aging, which defence systems and antioxidants provide the greatest degree of protection, what damage accumulates as cells age and which genetic systems are activated as during the process.Read moreRead less
Modulating the molecular and cellular physiology of ageing skeletal muscle. Understanding the underlying mechanisms of how ageing affects muscle is of increasing importance to the community as the number of older persons in the population continues to escalate and the age of retirement increases. Old muscles are slower and weaker than young muscles, and are more easily injured. This proposal is focussed on developing safe therapies to prevent or reverse these age-related effects. Making old musc ....Modulating the molecular and cellular physiology of ageing skeletal muscle. Understanding the underlying mechanisms of how ageing affects muscle is of increasing importance to the community as the number of older persons in the population continues to escalate and the age of retirement increases. Old muscles are slower and weaker than young muscles, and are more easily injured. This proposal is focussed on developing safe therapies to prevent or reverse these age-related effects. Making old muscles young again, is a research strategy that will promote healthy ageing and enable older Australians to enjoy a better quality of life.Read moreRead less
Characterisation of molecular regulation of telomerase and telomeres by p53 in cell ageing. Telomeres, the ends of chromosomes shorten as a function of cell division, and thereby limit cell lifespan. Telomerase synthesizes telomeres and thus renders cells immortal. Recently, we found that p53, a protein with an important role in cell aging and in the uncontrolled growth of cancer, interacts with telomeres and telomerase by binding to the telomere proteins TRF1 and TRF2. This project will deciphe ....Characterisation of molecular regulation of telomerase and telomeres by p53 in cell ageing. Telomeres, the ends of chromosomes shorten as a function of cell division, and thereby limit cell lifespan. Telomerase synthesizes telomeres and thus renders cells immortal. Recently, we found that p53, a protein with an important role in cell aging and in the uncontrolled growth of cancer, interacts with telomeres and telomerase by binding to the telomere proteins TRF1 and TRF2. This project will decipher the mechanisms by which p53 regulates telomerase and telomeres, and establish the interrelationship of these proteins in regulating cell lifespan, death and immortalisation. It will provide important information for molecular intervention in cell ageing and immortalisation.Read moreRead less
Assessing gene function in the developing brain using zebrafish as a model system. As the average life expectancy in western countries rises there is an increasing incidence of mental health problems. Therapeutic approaches to both Alzhemier's and Parkinson's disease, as well as to brain injury following stroke, rely on a thorough understanding of how the brain develops. This is consistent with the everyday principle that if you want to fix something that is broken, then you need to understand h ....Assessing gene function in the developing brain using zebrafish as a model system. As the average life expectancy in western countries rises there is an increasing incidence of mental health problems. Therapeutic approaches to both Alzhemier's and Parkinson's disease, as well as to brain injury following stroke, rely on a thorough understanding of how the brain develops. This is consistent with the everyday principle that if you want to fix something that is broken, then you need to understand how it is put together in the first place. This project seeks to understand how the normal brain is wired together in the embryo and, in doing so it will expose novel targets for therapy in the aged.Read moreRead less