The biological and pathological functions of TDP-43. The social and economic burden of neurodegenerative such as MND is enormous. A key histopathological hallmark of this and many other related diseases are deposits of the protein TDP-43. Our research aims at understanding its largely unknown functions, for example by generating transgenic animal models. These will form the base for the development for a TDP-43-directed drug treatment. The national benefit of this research is manifold: by deciph ....The biological and pathological functions of TDP-43. The social and economic burden of neurodegenerative such as MND is enormous. A key histopathological hallmark of this and many other related diseases are deposits of the protein TDP-43. Our research aims at understanding its largely unknown functions, for example by generating transgenic animal models. These will form the base for the development for a TDP-43-directed drug treatment. The national benefit of this research is manifold: by deciphering basic biological mechanisms, patenting new data, developing treatment strategies for un-curable and fatal disorders, and expanding links to Australian biotech and international pharmaceutical companies.Read moreRead less
Identifying the pathways employed by growth hormone to regulate the proliferation of adult neural stem cells. As stem cells underpin the maintenance and regeneration of the brain and are known to decline in number and competence with age; understanding exactly how these cells are regulated is of broad national benefit. Furthermore, given the regulatory role of growth hormone throughout the body, insights gained from this project should lead to the discovery of novel therapeutic targets both with ....Identifying the pathways employed by growth hormone to regulate the proliferation of adult neural stem cells. As stem cells underpin the maintenance and regeneration of the brain and are known to decline in number and competence with age; understanding exactly how these cells are regulated is of broad national benefit. Furthermore, given the regulatory role of growth hormone throughout the body, insights gained from this project should lead to the discovery of novel therapeutic targets both within and outside the nervous system, ultimately leading to preventative and restorative strategies for maintaining good health. Finally, this Proposal is of significant national benefit as it will undoubtedly advance our knowledge base in stem cell biology, helping to maintain Australia as a global leader in stem cell research.Read moreRead less
The MIA mitochondrial import pathway: structure and function. Our aging population is increasingly susceptible to mitochondrial disease and Australia is vulnerable to the associated economic and social burden. This research will benefit Australia by contributing to a knowledge-based economy; identifying new pathways that can be targeted for therapeutic intervention; developing smarter and faster hybrid approaches that strengthen Australia's basic and strategic research capability; and forging ne ....The MIA mitochondrial import pathway: structure and function. Our aging population is increasingly susceptible to mitochondrial disease and Australia is vulnerable to the associated economic and social burden. This research will benefit Australia by contributing to a knowledge-based economy; identifying new pathways that can be targeted for therapeutic intervention; developing smarter and faster hybrid approaches that strengthen Australia's basic and strategic research capability; and forging new international links. In the future, this research will lead to new collaborations between academia and industry and the discovery of potential new drugs that would benefit the health of Australians, benefit the economy of our healthcare system and provide potential economic benefits through royalty streams.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
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
Inhibition of pro-inflammatory cytokine secretion- A new route to therapeutics of chronic inflammatory disease. Chronic inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease, affect millions of people leading to considerable suffering, economic loss and premature death. Anti-TNF treatments have recently shown success in the treatment of rheumatoid arthritis, inflammatory bowel disease and other conditions, however, a substantial number of patients (~50%) do not re ....Inhibition of pro-inflammatory cytokine secretion- A new route to therapeutics of chronic inflammatory disease. Chronic inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease, affect millions of people leading to considerable suffering, economic loss and premature death. Anti-TNF treatments have recently shown success in the treatment of rheumatoid arthritis, inflammatory bowel disease and other conditions, however, a substantial number of patients (~50%) do not respond to the current TNF treatments. Improved anti-TNF strategies would provide enhanced health outcomes and welcome relief to many Australians. In addition, the economic benefit of the TNF market is very substantial. Therefore the potential impact of this research is very high both for health care and economical potential.Read moreRead less
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
Intelligent scaffolds and methods for repair of osteochondral defects. Osteoarthritis (OA) produces articulation of bone against bone resulting in extreme pain and disability. Of all musculoskeletal disorders, osteoarthritis has the greatest social and economic implications worldwide. By 2030, it is projected that 9.3% of the adult population will suffer from arthritis, significantly affecting their quality of life and overall productivity. A tissue engineered product capable of repairing osteoc ....Intelligent scaffolds and methods for repair of osteochondral defects. Osteoarthritis (OA) produces articulation of bone against bone resulting in extreme pain and disability. Of all musculoskeletal disorders, osteoarthritis has the greatest social and economic implications worldwide. By 2030, it is projected that 9.3% of the adult population will suffer from arthritis, significantly affecting their quality of life and overall productivity. A tissue engineered product capable of repairing osteochondral defects that does not require revision over time but becomes fully integrated with the host tissue will have significant benefits. It will improve patient activity and quality of life, and significantly reduce current health care costs associated with osteoarthritis sufferers.Read moreRead less
Proteomics Analysis of Interactions Between Chaperonin 10 and Cell Surface Proteins. Specific interactions at the cell surface may induce downstream biological responses. In the case of chaperonin 10, Cpn10, interaction at the cell surface results in immunomodulation of the inflammatory response. Cell surface proteins that interact with Cpn10 have not been identified. This project will use chemical crosslinking and proteomic techniques to identify cell surface proteins that interact with Cpn10 a ....Proteomics Analysis of Interactions Between Chaperonin 10 and Cell Surface Proteins. Specific interactions at the cell surface may induce downstream biological responses. In the case of chaperonin 10, Cpn10, interaction at the cell surface results in immunomodulation of the inflammatory response. Cell surface proteins that interact with Cpn10 have not been identified. This project will use chemical crosslinking and proteomic techniques to identify cell surface proteins that interact with Cpn10 and structural features of Cpn10 involved in these interactions. These findings will providde leads for the development of immunomodulatory therapeutics based on Cpn10 interactions. Analytical technologies will be developed that are applicable to other interacting protein systems.Read moreRead less
A new model for secreton in epithelial cells. This proposal sets out to test a new model for secretion that we have developed in the light of recent experimental data. The project outcomes will advance our understanding of normal processes of secretion and may be important in understanding disease. We will develop cutting-edge techniques of microscopy which will place Australia at the forefront of this exciting field. The project will bring benefit to the Australian scientific community through ....A new model for secreton in epithelial cells. This proposal sets out to test a new model for secretion that we have developed in the light of recent experimental data. The project outcomes will advance our understanding of normal processes of secretion and may be important in understanding disease. We will develop cutting-edge techniques of microscopy which will place Australia at the forefront of this exciting field. The project will bring benefit to the Australian scientific community through interactions and collaborations with other scientists in Australia and internationally and will benefit early-career scientists, training them in novel methods and allowing them to develop their research expertise and profile and enabling them to compete on the world science stage. Read moreRead less