Stress-induced Genomic Instability As A Driver Of Adaptive Responses In Human Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$690,426.00
Summary
Growing experimental evidence suggests human cancer cells use evolutionary conserved programs to regulate their mutation rates in response to pharmacological agents, accelerating adaptation and the emergence of resistance. The purpose of our study is to identify the common molecular pathways and genetic mechanisms driving the regulation of mutation rates. Targeting of these pathways using a new generation of “anti-evolution” drugs is an attractive possibility for novel therapeutic approaches.
Identifying Target Genes For Novel Anti-epileptic Therapies In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$469,802.00
Summary
Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not respo ....Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not responding to current therapy. This project is designed to identify new biologic pathways which may be interrupted with drugs to prevent seizures in people with epilepsy. This project uses a procedure to induce mutations into genes in mice and then screens for mice which do not seize when challenged with a drug which generates seizures in mice. Genetic studies will identify the mutated genes and these will be used as potential targets for new therapies or will identify new biological pathway which should expand the use of future anti-epileptic drugs.Read moreRead less
Structural Studies On Cell Signalling Via The LIF Receptor And Gp130
Funder
National Health and Medical Research Council
Funding Amount
$453,943.00
Summary
The cytokines play important roles in the immune system during blood cell development and inflammation, and in nerve growth, bone remodeling, reproduction and heart development. Cell responses are initiated by a cytokine bringing together on the cell surface a receptor complex made up of multiple molecules. This project will investigate the atomic structure of the cell surface macromolecular complex, and hence the underlying mechanism by which cytokine signals are initiated.
Post-genomic investigation of the relict plastid and mitochondrion of malaria parasites. Malaria is a major global health problem. The malaria parasite has two substructures, a relict chloroplast and a mitochondrion, that are excellent targets for new and existing drugs. However, we do not know the key functions of these two compartments. The entire genetic blueprint (genome) is now available for the malaria parasite and I propose to determine exactly which parts of the genome service the rel ....Post-genomic investigation of the relict plastid and mitochondrion of malaria parasites. Malaria is a major global health problem. The malaria parasite has two substructures, a relict chloroplast and a mitochondrion, that are excellent targets for new and existing drugs. However, we do not know the key functions of these two compartments. The entire genetic blueprint (genome) is now available for the malaria parasite and I propose to determine exactly which parts of the genome service the relict chloroplast and mitochondria. This will sketch out a picture of their inner workings. Armed with this information we can take a rational approach to seeking an Achilles? Heel of malaria against which parasite-specific drugs can be developed.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
Unravelling the sub-nuclear complexity of the brain. Understanding the function of the brain is a major frontier of scientific research. The ability to increase knowledge of brain function is reliant upon the development of novel methods. This application will develop a novel approach for understanding the function of particular nerve cells. One outcome will be demonstration of the applicability of a novel method of benefit to all brain researchers. Another outcome will be increased understandin ....Unravelling the sub-nuclear complexity of the brain. Understanding the function of the brain is a major frontier of scientific research. The ability to increase knowledge of brain function is reliant upon the development of novel methods. This application will develop a novel approach for understanding the function of particular nerve cells. One outcome will be demonstration of the applicability of a novel method of benefit to all brain researchers. Another outcome will be increased understanding of one brain region that is known to contribute to the development of cardiovascular disease. It is expected that increased knowledge of brain function will lead to novel theories of brain disease and therapeutic strategies.Read moreRead less
A knockout approach to identifying genes involved in epidermal development and homeostasis. These studies will identify new genes which play a role in the development or maintenance of the skin, some of which may subsequently be shown to play a role in disease. The project capitalises on an investment of tens of millions of dollars by the Wellcome Trust in generating a significant cohort of knockout mice. Our involvement in this international initiative will ensure Australia's participation in ....A knockout approach to identifying genes involved in epidermal development and homeostasis. These studies will identify new genes which play a role in the development or maintenance of the skin, some of which may subsequently be shown to play a role in disease. The project capitalises on an investment of tens of millions of dollars by the Wellcome Trust in generating a significant cohort of knockout mice. Our involvement in this international initiative will ensure Australia's participation in a project at the forefront of mouse genetics, using cutting edge infrastructure and technologies to provide insights into the complement of genes involved in skin biology. Models of interest will be repatriated to Australia for further study capitalising on existing infrastructure provided through the NCRIS funding program. Read moreRead less
Developing technologies that support the genetic modification of rats. Rats and the mouse play critical roles in medical research. Until recently, the targeted genetic modification of a mammal was limited to the mouse. This was due to a technology that was unique to the mouse: embryonic stem (ES) cells. These cells have not been isolated from any other species. The recent development of animal cloning allows for an alternate strategy for targeting genes. We propose to develop cloning strate ....Developing technologies that support the genetic modification of rats. Rats and the mouse play critical roles in medical research. Until recently, the targeted genetic modification of a mammal was limited to the mouse. This was due to a technology that was unique to the mouse: embryonic stem (ES) cells. These cells have not been isolated from any other species. The recent development of animal cloning allows for an alternate strategy for targeting genes. We propose to develop cloning strategies in the rat that supports the genetic modification of this animal. The development of this technology will bring considerable benefits to the areas of physiological research and drug design.Read moreRead less
Blocking immune responses: a critical factor in herpesvirus virulence? The horse and poultry industries are two large, primarily rural based livestock production industries that are major contributors to the national economy. The research proposed in this project will improve our understanding of the pathogenesis of two important viral pathogens that are each a significant cost to their respective industry, and thus will ultimately reduce the cost of these two viruses to industry. In addition, ....Blocking immune responses: a critical factor in herpesvirus virulence? The horse and poultry industries are two large, primarily rural based livestock production industries that are major contributors to the national economy. The research proposed in this project will improve our understanding of the pathogenesis of two important viral pathogens that are each a significant cost to their respective industry, and thus will ultimately reduce the cost of these two viruses to industry. In addition, the technology developed during this project would have a global market and may be transferable to other viral pathogens of other domestic species.Read moreRead less
Creation of a non-venomous honey bee. On average, two Australians die from bee stings each year. Our goal is produce honey bees that do not have a dangerous sting.