The role of copper in the early ubiquitination pathway. This project aims to explore the role of copper in ageing and protein turnover. The removal of damaged or excess proteins is achieved by ubiquitin-tagging in all kingdoms of life. It has recently been observed that one of the earliest steps of this process appears to be driven by copper. This project aims to elaborate the precise biochemical mechanisms by which copper regulates this important tagging and protein turnover system. It proposes ....The role of copper in the early ubiquitination pathway. This project aims to explore the role of copper in ageing and protein turnover. The removal of damaged or excess proteins is achieved by ubiquitin-tagging in all kingdoms of life. It has recently been observed that one of the earliest steps of this process appears to be driven by copper. This project aims to elaborate the precise biochemical mechanisms by which copper regulates this important tagging and protein turnover system. It proposes to characterise the structure and function of a newly identified copper-dependent form of cell enzyme which could be involved in amplifying ubiquitin-tagged protein breakdown. Copper is essential for life in all domains. Identifying copper as a major regulator in protein clearance is important in understanding this fundamental biological machinery.Read moreRead less
Mannosyl transfer processes in leishmania and mycobacteria. The human diseases leishmaniasis and tuberculosis are caused by infectious microorganisms. We will target pathways to the biosynthesis and degradation of parasite-specific mannose containing metabolites that play essential roles in the ability of these pathogens to cause disease. We will develop new ways to study these pathways, and will synthesize novel substrates and inhibitors that will allow the development of antituberculosis and a ....Mannosyl transfer processes in leishmania and mycobacteria. The human diseases leishmaniasis and tuberculosis are caused by infectious microorganisms. We will target pathways to the biosynthesis and degradation of parasite-specific mannose containing metabolites that play essential roles in the ability of these pathogens to cause disease. We will develop new ways to study these pathways, and will synthesize novel substrates and inhibitors that will allow the development of antituberculosis and antileishmanial drugs. This project will contribute to our national competitiveness in the newly emerging area of chemical biology.Read moreRead less
Mannose metabolism in pathogenic microorganisms. Current treatments for tuberculosis and leishmaniasis are failing due to chronic underinvestment by the private sector and public agencies over many decades. The causative agents, the microorganisms Leishmania spp and Mycobacterium tuberculosis, respectively, use sugar processing pathways that differ from humans, and thus represent targets for new drugs. We will study two related sugar-processing biochemical pathways in these organisms. We will de ....Mannose metabolism in pathogenic microorganisms. Current treatments for tuberculosis and leishmaniasis are failing due to chronic underinvestment by the private sector and public agencies over many decades. The causative agents, the microorganisms Leishmania spp and Mycobacterium tuberculosis, respectively, use sugar processing pathways that differ from humans, and thus represent targets for new drugs. We will study two related sugar-processing biochemical pathways in these organisms. We will develop new ways to measure enzyme activity using mass spectrometry, and new reagents to clone several biosynthetic enzymes. Our work will lay a foundation for new antibiotics to combat these insidious diseases, and will foster Australian expertise in chemical biology and innovative basic science.Read moreRead less
Chemical tools for the study of mycobacterial glycolipid biosynthesis. Mycobacteria are responsible for human morbidity and mortality on a immense scale. The cell wall structure of these bacteria is extremely complex and offers many novel therapeutic opportunities. In this proposal we will use a synergetic interplay of chemistry, biochemistry and microbiology to study the biosynthesis of essential cell wall molecules conserved across all mycobacteria, the phosphatidylinositol mannosides. Substr ....Chemical tools for the study of mycobacterial glycolipid biosynthesis. Mycobacteria are responsible for human morbidity and mortality on a immense scale. The cell wall structure of these bacteria is extremely complex and offers many novel therapeutic opportunities. In this proposal we will use a synergetic interplay of chemistry, biochemistry and microbiology to study the biosynthesis of essential cell wall molecules conserved across all mycobacteria, the phosphatidylinositol mannosides. Substrates and inhibitors will be prepared and studied using novel biochemical and microbiological methods. This project will enhance our understanding of cell wall synthesis in mycobacteria and will lay the ground work for the discovery of novel antibiotics.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100125
Funder
Australian Research Council
Funding Amount
$330,000.00
Summary
Oxidative stress bioanalytical facility. The primary national benefit of this application is that it will provide a currently unavailable, state-of-the-art facility for Australian scientists to define precisely how changes in cellular redox state contribute to biological processes relevant to health and diseases. The facility will uniquely complement, and in many cases integrate with existing facilities in this area of research in Australia. It will act as a platform for major national and inter ....Oxidative stress bioanalytical facility. The primary national benefit of this application is that it will provide a currently unavailable, state-of-the-art facility for Australian scientists to define precisely how changes in cellular redox state contribute to biological processes relevant to health and diseases. The facility will uniquely complement, and in many cases integrate with existing facilities in this area of research in Australia. It will act as a platform for major national and international research collaborations, develop cutting-edge technology and unique local skills, and contribute to Australia maintaining a leading position in redox-related research in biology and medicine. In doing so, the facility will increase the likelihood of gaining future, value-adding funding.Read moreRead less
Understanding and controlling the construction of molecular electronic and photovoltaic devices using nucleic acids. The efficient generation and use of energy is arguably the most pressing problem the world faces today. This project will enable the construction of molecular electronic and energy generation devices with increased efficiency, and will impact the fields of bio-organic chemistry and material science. Australia will benefit from the cheap and efficient energy produced by these new e ....Understanding and controlling the construction of molecular electronic and photovoltaic devices using nucleic acids. The efficient generation and use of energy is arguably the most pressing problem the world faces today. This project will enable the construction of molecular electronic and energy generation devices with increased efficiency, and will impact the fields of bio-organic chemistry and material science. Australia will benefit from the cheap and efficient energy produced by these new environmentally benign energy generation and transducing devices. A secondary benefit will arise when these devices are applied to medical diagnostics for early detection of diseases. Economic and environmental benefits for the Australian community and Australia's development as a knowledge-based economy will be the result.Read moreRead less
Molecular machines: regulation of the catalysis and rotation of the enzyme ATP synthase. This project aims to elucidate the regulation of the molecular machine ATP synthase. ATP synthase is an enzyme that performs a critical role in all cells - the synthesis of ATP, the universal biological energy currency. It is known that the enzyme operates via rotation of a central stalk which is driven by a hydrogen ion gradient across a membrane. Constructs of this molecule have been envisaged in the desig ....Molecular machines: regulation of the catalysis and rotation of the enzyme ATP synthase. This project aims to elucidate the regulation of the molecular machine ATP synthase. ATP synthase is an enzyme that performs a critical role in all cells - the synthesis of ATP, the universal biological energy currency. It is known that the enzyme operates via rotation of a central stalk which is driven by a hydrogen ion gradient across a membrane. Constructs of this molecule have been envisaged in the design of future biological nano-motors. Our work will provide an understanding of the regulation of this enzyme with potential application in the control of nano-motors.Read moreRead less
How are plants responding to damage by oxidizing air pollutants? This project aims to obtain detailed understanding of the chemical processes by which the air pollutants ozone and nitrogen dioxide damage plants. Through an interdisciplinary approach involving physical organic chemistry and analytical biochemistry, this project intends to discover important reactions between plant biomolecules and air pollutants, identify biochemical mechanisms for pollution damage in crop model plants and reveal ....How are plants responding to damage by oxidizing air pollutants? This project aims to obtain detailed understanding of the chemical processes by which the air pollutants ozone and nitrogen dioxide damage plants. Through an interdisciplinary approach involving physical organic chemistry and analytical biochemistry, this project intends to discover important reactions between plant biomolecules and air pollutants, identify biochemical mechanisms for pollution damage in crop model plants and reveal the plant defence mechanism at the molecular level. Expected outcomes include the much-needed scientific foundations to support the development of more pollution-resilient crops in the future, ultimately enabling a breakthrough for the triple challenge of environmental pollution, climate change and food security.Read moreRead less
The Design and Synthesis of Inhibitors of Human Immunodeficiency (HIV) Budding. We have a very exciting and revolutionary approach to drug design by exploiting the exquisite potent action of peptides and at the same time overcome their shortcomings as drug candidates in that they are rapidly degraded in the body. We do this by slightly modifying their chemical structure but at the same time maintaining their biological activity. We will apply this new approach to a novel protein target to inhibi ....The Design and Synthesis of Inhibitors of Human Immunodeficiency (HIV) Budding. We have a very exciting and revolutionary approach to drug design by exploiting the exquisite potent action of peptides and at the same time overcome their shortcomings as drug candidates in that they are rapidly degraded in the body. We do this by slightly modifying their chemical structure but at the same time maintaining their biological activity. We will apply this new approach to a novel protein target to inhibit one of the main steps in the budding of Human Immunodeficiency (HIV) from infected cells. This unique combination of novel chemistry and drug design target makes this project highly innovative and with enormous potential to accelerate the identification of new drugs for HIV treatment.Read moreRead less