Nanoprobe and Microprobe Spectroscopic Techniques in Drug Design, Probing Mechanisms of Diseases, and Bioinorganic Chemistry. Nanoprobe and microprobe spectroscopic techniques offer unparalleled opportunities to probe the structures and distributions of drugs, carcinogens, and biomolecules in cultured cells and tissues. Such techniques represent new frontiers in understanding in vivo metabolic processes at the molecular level, as well as providing unprecedented information on the metabolism and ....Nanoprobe and Microprobe Spectroscopic Techniques in Drug Design, Probing Mechanisms of Diseases, and Bioinorganic Chemistry. Nanoprobe and microprobe spectroscopic techniques offer unparalleled opportunities to probe the structures and distributions of drugs, carcinogens, and biomolecules in cultured cells and tissues. Such techniques represent new frontiers in understanding in vivo metabolic processes at the molecular level, as well as providing unprecedented information on the metabolism and distributions of pharmaceuticals and toxins involved in the treatment and cause of diseases, such as cancer. This project is aimed at pushing the boundaries of nanoprobe and microprobe (X-ray absorption, SRIXE, PIXE, Raman and two-photon fluorescence) techniques for such applications.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
Streamlining the dynamin epilepsy drug pipeline. Epilepsy affects up to one percent of Australia's population, yet one in three fail to respond to current medications. Our results will greatly impact on development of future epilepsy therapy. Identification of a new target for epileptic will allow better drug design to improve the potency of our lead drugs. This holds hope that new generation drugs will be more effective. The drugs are predicted to have fewer complications and side-effects. Th ....Streamlining the dynamin epilepsy drug pipeline. Epilepsy affects up to one percent of Australia's population, yet one in three fail to respond to current medications. Our results will greatly impact on development of future epilepsy therapy. Identification of a new target for epileptic will allow better drug design to improve the potency of our lead drugs. This holds hope that new generation drugs will be more effective. The drugs are predicted to have fewer complications and side-effects. The outcome has the potential to vastly improve prospects for up to 200,000 Australians. Intellectual property (IP) retained in Australia will generate future biotechnology industry. The novel chemical biological approaches will facilitate training of future generations of Australian scientists.Read moreRead less
3D Structure determination of biomacromolecular assemblies from sparse data. This project has direct impact on pharmaceutical research: Biomacromolecular interactions are key points for pharmaceutical intervention and detailed structural knowledge of dynamic protein interactions can significantly accelerate drug development. Australia has invested in expensive instrumentation that can be used with new laboratory methods to obtain information on delicately balanced biomacromolecular interactions, ....3D Structure determination of biomacromolecular assemblies from sparse data. This project has direct impact on pharmaceutical research: Biomacromolecular interactions are key points for pharmaceutical intervention and detailed structural knowledge of dynamic protein interactions can significantly accelerate drug development. Australia has invested in expensive instrumentation that can be used with new laboratory methods to obtain information on delicately balanced biomacromolecular interactions, and how they malfunction in disease. This project will provide a computational framework to increase the impact of this investment by integrating measurements from a range of novel technologies and developing understanding of changes in structure of large protein complexes in different functional states.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
Targeting mitochondrial dysfunction in disease. Defects in mitochondria, the energy producing compartments within cells, lead to severe neurodegenerative diseases and contribute to the development of cancer. Treatment for such diseases caused by mutations in mitochondrial DNA remains unsatisfactory and mostly confined to supportive measures. The identification of proteins that regulate gene expression within mitochondria provides an unexplored resource of potential disease modulators and drug ta ....Targeting mitochondrial dysfunction in disease. Defects in mitochondria, the energy producing compartments within cells, lead to severe neurodegenerative diseases and contribute to the development of cancer. Treatment for such diseases caused by mutations in mitochondrial DNA remains unsatisfactory and mostly confined to supportive measures. The identification of proteins that regulate gene expression within mitochondria provides an unexplored resource of potential disease modulators and drug targets. This research will lead to new strategies in the design of improved anticancer drugs, which is an important Australian research priority that will promote and maintain good health, and provide potential commercial outcomes.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
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
Single Molecule Studies of Replisomal Function. It has recently become possible to watch the copying of DNA molecules with a specialized microscope in real time. This process requires assembly of a complex molecular machine on the DNA, followed by triggering of its function, and yields exquisitely detailed information about how the machine works. In this new collaboration between scientists in Australia and the U.S.A., we will assemble these machines on single DNA molecules, watch how they work ....Single Molecule Studies of Replisomal Function. It has recently become possible to watch the copying of DNA molecules with a specialized microscope in real time. This process requires assembly of a complex molecular machine on the DNA, followed by triggering of its function, and yields exquisitely detailed information about how the machine works. In this new collaboration between scientists in Australia and the U.S.A., we will assemble these machines on single DNA molecules, watch how they work and simultaneously measure the very small forces that the machines generate. This will give Australian scientists access to a new technology for studying molecular machines.Read moreRead less