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
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
Detecting stress-induced changes to subcellular copper pools in brain cells. Copper (Cu) plays essential roles in the functioning of brain cells, but the regulation and activity of this metal is poorly understood. This project aims to map sub-cellular Cu pools in brain cells, with particular emphasis on the effects of cellular stresses on these pools. These studies are expected to contribute important new methods for the study of Cu biology, and could provide valuable information about how Cu ho ....Detecting stress-induced changes to subcellular copper pools in brain cells. Copper (Cu) plays essential roles in the functioning of brain cells, but the regulation and activity of this metal is poorly understood. This project aims to map sub-cellular Cu pools in brain cells, with particular emphasis on the effects of cellular stresses on these pools. These studies are expected to contribute important new methods for the study of Cu biology, and could provide valuable information about how Cu homeostasis is maintained or perturbed under various stresses. In the future, this work is expected to form the basis of studies of brain Cu pools in neurodegenerative diseases.Read moreRead less
Expanding the molecular tool set for structural studies of proteins and their complexes. Many applications in medical science and drug development depend on our ability to determine the 3D structures of proteins, protein assemblies and protein-ligand complexes. This project will develop novel lanthanide-binding tags and crosslinking agents that can be coupled to unnatural amino acids introduced into proteins with advanced protein chemistry techniques. These new tools will facilitate the collecti ....Expanding the molecular tool set for structural studies of proteins and their complexes. Many applications in medical science and drug development depend on our ability to determine the 3D structures of proteins, protein assemblies and protein-ligand complexes. This project will develop novel lanthanide-binding tags and crosslinking agents that can be coupled to unnatural amino acids introduced into proteins with advanced protein chemistry techniques. These new tools will facilitate the collection of structure restraints by nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and mass spectrometry, which are needed to generate accurate models of proteins and their complexes with other molecules. Major beneficial outcome will include an increase in the number of protein targets amenable to rational drug design and improved methods for generating new drug leads.Read moreRead less
Group 13 Mixed Halide-Hydride and Rare Earth Complexes - New Selective Chiral Hydridic or Low Valent Reducing Agents. This project will make a landmark contribution to two areas of metallohydride chemistry. Both studies will utilise and develop metals that have traditionally been mined and exported from these shores while concurrently imported as value added products at vastly inflated cost. This research will identify knock-on applications in order to stem this financial bias. The new paths to ....Group 13 Mixed Halide-Hydride and Rare Earth Complexes - New Selective Chiral Hydridic or Low Valent Reducing Agents. This project will make a landmark contribution to two areas of metallohydride chemistry. Both studies will utilise and develop metals that have traditionally been mined and exported from these shores while concurrently imported as value added products at vastly inflated cost. This research will identify knock-on applications in order to stem this financial bias. The new paths to rare earth (= Ln) hydrides will have broad industrial appeal, particularly for new materials, where, like similar group 13 materials, they may be used in the deposition of Ln films or even as precursors to superconducting solids. It is anticipated industrial collaboration will ensue. Australia will be promoted as a developer and innovator of frontier technologies.Read moreRead less
Enhancing single-molecule magnets. This project aims to design, synthesise and investigate single-molecule magnets that can function at higher temperatures for use in quantum computing and molecular spintronics. Materials science increasingly benefit from molecular approaches, and lanthanoid-based single-molecule magnets could achieve otherwise inaccessible technological developments such as the development of molecular materials for quantum computing and molecular spintronics. Advances in funda ....Enhancing single-molecule magnets. This project aims to design, synthesise and investigate single-molecule magnets that can function at higher temperatures for use in quantum computing and molecular spintronics. Materials science increasingly benefit from molecular approaches, and lanthanoid-based single-molecule magnets could achieve otherwise inaccessible technological developments such as the development of molecular materials for quantum computing and molecular spintronics. Advances in fundamental chemistry are anticipated, and this project is expected to benefit Australia's participation in related high-end technology industries.Read moreRead less
Development and Biological Chemistry of Novel Platinum Anti-Cancer Agents. "Rule-breakers", platinum anticancer complexes that do not follow the well established structure/activity relationships, have emerged as the way forward in the treatment of cancer resistant to the current generation of drugs and in reducing side effects. We have developed two new groups of "rule-breakers" and these have already demonstrated highly promising anticancer activity and novel biological behaviour. In this proje ....Development and Biological Chemistry of Novel Platinum Anti-Cancer Agents. "Rule-breakers", platinum anticancer complexes that do not follow the well established structure/activity relationships, have emerged as the way forward in the treatment of cancer resistant to the current generation of drugs and in reducing side effects. We have developed two new groups of "rule-breakers" and these have already demonstrated highly promising anticancer activity and novel biological behaviour. In this project we will (i) prepare new anticancer active platinum complexes based on these two highly promising groups of compounds and (ii) determine how these drugs work and what happens to them when in biological environments.Read moreRead less
Defining mechanisms of action of novel alpha-conotoxins at nicotinic receptor-channels. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a gr ....Defining mechanisms of action of novel alpha-conotoxins at nicotinic receptor-channels. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a greater understanding of how the nervous system functions. This knowledge will help in the design of new drugs to treat a variety of diseases and disorders. Essentially we will use a chemical armoury developed by the cone snail to design state-of-the-art mini-protein drugs.Read moreRead less
Thin Films of Oxide Ceramics. Aluminium oxide films are used extensively in the Australian industries of Protective & Decorative Coatings (examples include door-knobs and cutting-tools). The industry will be offered a remarkably simple process for preparation of high quality films. In the microelectronic industry, the uses of aluminium oxide films as a dielectric alternative to silicon dioxide has just started to emerge world - wide and this new process would make a dramatic impact with commerci ....Thin Films of Oxide Ceramics. Aluminium oxide films are used extensively in the Australian industries of Protective & Decorative Coatings (examples include door-knobs and cutting-tools). The industry will be offered a remarkably simple process for preparation of high quality films. In the microelectronic industry, the uses of aluminium oxide films as a dielectric alternative to silicon dioxide has just started to emerge world - wide and this new process would make a dramatic impact with commercial benefits for Australia. Read moreRead less