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
Validating protozoa-specific drug targets using peptides from biodiverse gene fragment libraries. Cryptosporidium and the trypanosomes are protozoan parasites, which have a global impact on the health, survival and economic development of millions of people and animals world wide. New therapies for the diseases they cause are urgently required. We describe a novel means of identifying protozoa-specific peptides that will inhibit the formation of essential protein complexes, which have no effect ....Validating protozoa-specific drug targets using peptides from biodiverse gene fragment libraries. Cryptosporidium and the trypanosomes are protozoan parasites, which have a global impact on the health, survival and economic development of millions of people and animals world wide. New therapies for the diseases they cause are urgently required. We describe a novel means of identifying protozoa-specific peptides that will inhibit the formation of essential protein complexes, which have no effect on the mammalian host. Candidate peptides will then be used to validate these protein complexes as new targets for the development of peptide-based therapeutic compounds. This project will validate novel targets for the development of new treatments for these diseases.Read moreRead less
In vitro expression and crystallization of proteins from the thermohalophile, Halothermothrix orenii. The project proposal is to develop enabling state-of-the-art protein technologies for biotechnology. We will for the first time develop a rapid and high throughput technique for the expression, purification and crystallisation of proteins from the extreme thermohalophile, Halothermothrix orenii. This important break through in protein technology will assist in determining structure and function ....In vitro expression and crystallization of proteins from the thermohalophile, Halothermothrix orenii. The project proposal is to develop enabling state-of-the-art protein technologies for biotechnology. We will for the first time develop a rapid and high throughput technique for the expression, purification and crystallisation of proteins from the extreme thermohalophile, Halothermothrix orenii. This important break through in protein technology will assist in determining structure and function relationships of thermohalophilic proteins. It is expected that such an understanding together with comparative bioinformatics will assist researchers to develop "designer proteins" with improved functions for different uses in biotechnology. It is also expected that this technology will be amenable for use with other thermohalophilic microbes.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
Specific gene inhibition through functional genomics and high through-put small molecule screening. This project will utilise functional genomic technologies in an attempt to identify genes in childhood neuroblastoma as potential candidates for the future development of molecular-targeted gene therapy. By screening large 'libraries' of chemical compounds, we aim to identify compounds with the ability to specifically inhibit these gene targets. This project will therefore define novel molecular t ....Specific gene inhibition through functional genomics and high through-put small molecule screening. This project will utilise functional genomic technologies in an attempt to identify genes in childhood neuroblastoma as potential candidates for the future development of molecular-targeted gene therapy. By screening large 'libraries' of chemical compounds, we aim to identify compounds with the ability to specifically inhibit these gene targets. This project will therefore define novel molecular targets and possibly facilitate the future development of new therapeutic approaches to treating neuroblastoma. In addition, the project will develop know-how that can be utilised by both the industry partner and the broader research community and will introduce to Australian science novel techniques and skills. Read moreRead less
Elucidation of genetic and physiological factors controlling biosynthesis of sesquiterpenoids in sandalwood, Santalum spp. Plantation sandalwood removes pressure from natural populations and is a profitable long term investment. Australia is in a highly competitive position with regards to market supply but this cannot be taken for granted. This research seeks to understand the complex biology of sandalwood using the latest genomic and molecular technologies. This knowledge will be applied thro ....Elucidation of genetic and physiological factors controlling biosynthesis of sesquiterpenoids in sandalwood, Santalum spp. Plantation sandalwood removes pressure from natural populations and is a profitable long term investment. Australia is in a highly competitive position with regards to market supply but this cannot be taken for granted. This research seeks to understand the complex biology of sandalwood using the latest genomic and molecular technologies. This knowledge will be applied through directed, marker-assisted tree selection and improved plantation management. Ultimately we are developing a highly advanced production system with which Australia can lead Sandalwood production. Sandalwood plantations use a variety of native perennial hosts, increase biodiversity, help manage underground water resources and address carbon sequestration demands.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
Cell type-specific transgene expression to increase Fe content in cereal grains. The grains industry forms a vital part of the Australian economy and farm sector. Increased iron concentrations of wheat and other cereal grains would greatly increase their nutritional value for people worldwide, thereby increasing their market value and profitability for farmers. High iron wheat would also lower the production costs of many Australian wheat products by reducing or eliminating the need for iron for ....Cell type-specific transgene expression to increase Fe content in cereal grains. The grains industry forms a vital part of the Australian economy and farm sector. Increased iron concentrations of wheat and other cereal grains would greatly increase their nutritional value for people worldwide, thereby increasing their market value and profitability for farmers. High iron wheat would also lower the production costs of many Australian wheat products by reducing or eliminating the need for iron fortification of wheat flour. High iron cereals promote healthy development of young Australians and can improve preventative healthcare by reducing the incidence of iron deficiency anaemia and biochemical deficiency.Read moreRead less
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
Enhanced biocatalysis in organic solvents for pharmaceutical biotransformation. Enzymes such as hydrolases play an important role in biotechnology because of their extreme versatility with respect to substrate specificity and stereoselectivity. The use of lipases as catalysts for optical isomer-specific organic reactions is often limited by unacceptably low enantioselectivities. We will investigate recombinant enzymes cloned from thermophilic lipolytic bacteria for synthetic reactions in orga ....Enhanced biocatalysis in organic solvents for pharmaceutical biotransformation. Enzymes such as hydrolases play an important role in biotechnology because of their extreme versatility with respect to substrate specificity and stereoselectivity. The use of lipases as catalysts for optical isomer-specific organic reactions is often limited by unacceptably low enantioselectivities. We will investigate recombinant enzymes cloned from thermophilic lipolytic bacteria for synthetic reactions in organic solvents, especially chiral resolution of mixtures in the production of pharmaceutical intermediates. Genetic improvement of lipase enantiospecificity and regioselectivity will be achieved using in vitro evolution by recombination and screening. The outcome will be cost-effective production superior biocatalysts with specifically enhanced regiospecific, enantioselective and hydrolytic characteristics.
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