Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Resistance by cancers to established chemotherapeutics is a growing problem in the community and one that demands the development of new strategies. Chelators that target the essential element iron within cancer cells represent a novel and promising approach to this problem. The Chief Investigators represent a unique combination of expertise in coordination chemistry and the biochemistry of iron chelati ....Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Resistance by cancers to established chemotherapeutics is a growing problem in the community and one that demands the development of new strategies. Chelators that target the essential element iron within cancer cells represent a novel and promising approach to this problem. The Chief Investigators represent a unique combination of expertise in coordination chemistry and the biochemistry of iron chelation. They have discovered and characterised new chelators that show marked anticancer activity, and act by a new mechanism that overcomes problems of resistance. In this project they will pursue a course that will lead to a greater understanding of how these compounds work with the outcome that new effective anticancer drugs may emerge.Read moreRead less
Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Iron is essential for life, but iron-overload is a potentially fatal condition. There is no natural mechanism to excrete iron in humans, so patients suffering from iron-overload disorders are treated with the chelator Desferal to enable iron excretion typically from an early age. Desferal is orally ineffective and must be given by subcutaneous infusion (12-24h, 5-6 days/week) resulting in poor patient c ....Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Iron is essential for life, but iron-overload is a potentially fatal condition. There is no natural mechanism to excrete iron in humans, so patients suffering from iron-overload disorders are treated with the chelator Desferal to enable iron excretion typically from an early age. Desferal is orally ineffective and must be given by subcutaneous infusion (12-24h, 5-6 days/week) resulting in poor patient compliance. We will conduct critical chemical and biological experiments with a new series of potentially orally active iron chelators identified in our lab. The results from this project will be vital for the development of these compounds as pharmaceuticals.Read moreRead less
Metal Clips for Folding Peptides. Large protein molecules fold into shapes that are important for their function. These shapes are defined by secondary structures stabilised by hydrogen bonds, packing effects, and sometimes also by the binding of metal ions. Smaller peptides corresponding to these secondary structures tend to adopt only random structures in solution, away from the stabilising environment of the protein. In this project metal ions are used to clip together components of small pe ....Metal Clips for Folding Peptides. Large protein molecules fold into shapes that are important for their function. These shapes are defined by secondary structures stabilised by hydrogen bonds, packing effects, and sometimes also by the binding of metal ions. Smaller peptides corresponding to these secondary structures tend to adopt only random structures in solution, away from the stabilising environment of the protein. In this project metal ions are used to clip together components of small peptides, thereby stabilising secondary structures (alpha helices) identical to those adopted by proteins. Small peptides so constrained may reproduce some properties of proteins, such as interactions with biological receptors.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668382
Funder
Australian Research Council
Funding Amount
$1,000,000.00
Summary
e-Research Infrastructure for the Molecular and Materials Structure Sciences. Understanding molecular and materials structure in atomic detail is vital to a knowledge-based economy and a healthy society. The development of smart materials, nanotechnological devices, hydrogen storage materials, molecular switches, magnets and sensors, for example, depends on knowledge of three-dimensional atomic structure. Cures for illnesses such as SARS, AIDS and Alzheimer's disease and understanding the aging ....e-Research Infrastructure for the Molecular and Materials Structure Sciences. Understanding molecular and materials structure in atomic detail is vital to a knowledge-based economy and a healthy society. The development of smart materials, nanotechnological devices, hydrogen storage materials, molecular switches, magnets and sensors, for example, depends on knowledge of three-dimensional atomic structure. Cures for illnesses such as SARS, AIDS and Alzheimer's disease and understanding the aging process depends on knowledge of biomolecular structure. The deployment and development of automation-enhanced remote access to structural instruments through the web will greatly enhance Australian structure-based research, and make this science accessible to the public. Read moreRead less
DEVELOPMENT OF A NOVEL BIOMATERIAL FOR BONE TISSUE ENGINEERING. Tissue engineering of bone is emerging as a viable therapy for treating large defects in load-bearing bone. We wish to develop methods for combining novel heparan sulphate molecules (known to deliver growth factors to cell surfaces and thereby cause changes in bone cell phenotype) with load-bearing, macro-porous, biodegradable mineral/polymer biomaterials. Through the study of release profiles, protein adsorption and cell responses ....DEVELOPMENT OF A NOVEL BIOMATERIAL FOR BONE TISSUE ENGINEERING. Tissue engineering of bone is emerging as a viable therapy for treating large defects in load-bearing bone. We wish to develop methods for combining novel heparan sulphate molecules (known to deliver growth factors to cell surfaces and thereby cause changes in bone cell phenotype) with load-bearing, macro-porous, biodegradable mineral/polymer biomaterials. Through the study of release profiles, protein adsorption and cell responses to these derivatised biomaterials, a novel approach to bone replacement materials can be developed.Read moreRead less
Gold-based mitochondria targeted chemotherapeutics: mechanistic studies probing interactions with thiol and selenol containing proteins. Cancer affects one in four Australians and prostate cancer is the most commonly diagnosed and second leading cause of male cancer deaths, for which there is currently no effective treatment. Current chemotherapeutics must overcome drug resistance and lack of selectivity between tumour and normal cells. To circumvent these problems we are investigating gold-base ....Gold-based mitochondria targeted chemotherapeutics: mechanistic studies probing interactions with thiol and selenol containing proteins. Cancer affects one in four Australians and prostate cancer is the most commonly diagnosed and second leading cause of male cancer deaths, for which there is currently no effective treatment. Current chemotherapeutics must overcome drug resistance and lack of selectivity between tumour and normal cells. To circumvent these problems we are investigating gold-based compounds, which act by a novel mechanism. The research will lead to new strategies in the design of improved anticancer drugs, an important Australian research priority that will promote and maintain good health. Other benefits arise from training PhD students with interdisciplinary skills for Australian biotechnology industries.Read moreRead less
Functional and structural characterisation of Defective embryo and meristems (Dem) proteins involved in plant development. The proposed research will lead to advances in understanding the regulation of plant development, a process impacting on agriculture, environmental management and human health, areas designated as national research priorities. This understanding is required for modifying plant growth and architecture to fit particular environments, for example generating plants with more ext ....Functional and structural characterisation of Defective embryo and meristems (Dem) proteins involved in plant development. The proposed research will lead to advances in understanding the regulation of plant development, a process impacting on agriculture, environmental management and human health, areas designated as national research priorities. This understanding is required for modifying plant growth and architecture to fit particular environments, for example generating plants with more extensive and deeper roots to mine the soil moisture and nutrients to enhance crop productivity in Australia, and maintaining the competitive advantage of Australian agriculture in view of the range of environmental conditions encountered in this country. The project will also contribute to the health of the Australian population through consumable plants in the diet.Read moreRead less
Understanding and Inhibiting the P450 CYP24 enzyme, a target for cancer chemotherapeutics. This project falls within the National Research Priority of Promoting and Maintaining Good Health in the category of ageing well and productively. CYP24 inhibition provides a particular target for breast and prostate cancer which are the second leading cause of death in women and men, respectively. The proposed research will result in the production of CYP24 inhibitors that will be assessed in vivo at th ....Understanding and Inhibiting the P450 CYP24 enzyme, a target for cancer chemotherapeutics. This project falls within the National Research Priority of Promoting and Maintaining Good Health in the category of ageing well and productively. CYP24 inhibition provides a particular target for breast and prostate cancer which are the second leading cause of death in women and men, respectively. The proposed research will result in the production of CYP24 inhibitors that will be assessed in vivo at the Hanson Institute in Adelaide as potential anti-cancer drugs. Finally, there is a significant benefit in technology transfer to Australia from our collaborators in the USA in the field of computer aided inhibitor design.Read moreRead less
Coenzyme Q as a measure of environmental stress in aquatic ecosystems. Australia's marine and freshwater water resources including high profile regions such as the Great Barrier Reef and the Murray-Darling River system are under increasing threat. This project is significant as it aims to provide a rapid tool to quantify low-level impacts in aquatic systems and provide a novel and accurate early-warning-system of stress within aquatic environments. Through the innovative development of an assay ....Coenzyme Q as a measure of environmental stress in aquatic ecosystems. Australia's marine and freshwater water resources including high profile regions such as the Great Barrier Reef and the Murray-Darling River system are under increasing threat. This project is significant as it aims to provide a rapid tool to quantify low-level impacts in aquatic systems and provide a novel and accurate early-warning-system of stress within aquatic environments. Through the innovative development of an assay system from proven biomedical technologies it will be possible to deliver a significant community benefit by providing an early warning mechanism for the combined effects of urban and industrial impacts on our invaluable marine and freshwater resources.Read moreRead less
The development of copper-free click chemistry to label biomolecules within living cells. Understanding how cells work is central to modern advances in biomedical science, however many cellular processes are invisible to the researcher because of a lack of appropriate tools. This proposal will apply modern chemistry approaches to the design of new chemical tools for visualising biomolecules within living cells and for investigating cell function. This project brings together experts in chemistry ....The development of copper-free click chemistry to label biomolecules within living cells. Understanding how cells work is central to modern advances in biomedical science, however many cellular processes are invisible to the researcher because of a lack of appropriate tools. This proposal will apply modern chemistry approaches to the design of new chemical tools for visualising biomolecules within living cells and for investigating cell function. This project brings together experts in chemistry, stem cells and malaria and has applications for development of much needed new therapeutics. This research will advance biomedical research and generate new discoveries for a competitive advantage for Australian science, with potential economic return for the nation.Read moreRead less