Gene targeting in the rat germ cell. The rat plays a central role in both medical research and the drug development process. Unfortunately key technologies supporting the genetic modification of the rat are currently unavailable. The development of such technology would dramatically improve the utility of the rat in many areas of medical research as well as for the pharmaceutical industry. This project proposes to develop methods to perform gene targeting experiments in the germ cells of the ....Gene targeting in the rat germ cell. The rat plays a central role in both medical research and the drug development process. Unfortunately key technologies supporting the genetic modification of the rat are currently unavailable. The development of such technology would dramatically improve the utility of the rat in many areas of medical research as well as for the pharmaceutical industry. This project proposes to develop methods to perform gene targeting experiments in the germ cells of the male rat. Successful manipulation of these cells will represent a major breakthrough towards the ultimate goal of manipulating the rat genome.Read moreRead less
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.
Towards the development of a novel live vaccine for the control of Glässer's disease (Haemophilus parasuis), a globally significant respiratory disease of swine. Respiratory diseases are common in intensively housed pigs, costing the Australian industry millions of dollars in lost production annually. Glässer's is a highly contagious and often fatal respiratory disease of pigs. Antibiotic therapy is expensive and often results in the emergence of antibiotic resistant organisms. There is also a t ....Towards the development of a novel live vaccine for the control of Glässer's disease (Haemophilus parasuis), a globally significant respiratory disease of swine. Respiratory diseases are common in intensively housed pigs, costing the Australian industry millions of dollars in lost production annually. Glässer's is a highly contagious and often fatal respiratory disease of pigs. Antibiotic therapy is expensive and often results in the emergence of antibiotic resistant organisms. There is also a trend to move away from the use of antibiotics in food production animals. Current vaccines are based on inactivated preparations and do not offer a high level of immune protection. Therefore, there is a great need worldwide for a live vaccine for the effective control of Glässer's disease.Read moreRead less
Molecular, physiological and environmental regulation of toxic prussic acid levels (cyanogenesis) in forage sorghum. Forage sorghum is grown widely in dry, tropical areas of Australia. The leaves contain dhurrin, a natural defence product that liberates prussic acid (cyanide) when leaf tissue is disrupted (eg when chewed). The problem is that young plants or those experiencing drought are highly toxic, resulting in financial loss through reduced nutritive value, livestock loss and wasted feed. U ....Molecular, physiological and environmental regulation of toxic prussic acid levels (cyanogenesis) in forage sorghum. Forage sorghum is grown widely in dry, tropical areas of Australia. The leaves contain dhurrin, a natural defence product that liberates prussic acid (cyanide) when leaf tissue is disrupted (eg when chewed). The problem is that young plants or those experiencing drought are highly toxic, resulting in financial loss through reduced nutritive value, livestock loss and wasted feed. Using new, non-GM technology we will identify novel genetically altered sorghum lines with negligible prussic acid. Lines with enhanced levels could be used as soil biofumigants. Breeders can use this germplasm to develop varieties tailored for increasingly dry Australian conditions. The new varieties with controlled dhurrin content will be suitable for export.Read moreRead less