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Synthesis of stimuli-responsive star polymers for controlled drug delivery. The project aims to prepare novel star polymers suitable for drug delivery via controlled radical polymerization techniques. Such star polymers can be employed to release drugs within the human body in a controlled manner over time and are thus able to target specific sites, i.e. a tumor. The release characterisitics are be influenced by the structure and the size of the star polymer, which can easily be altered via cont ....Synthesis of stimuli-responsive star polymers for controlled drug delivery. The project aims to prepare novel star polymers suitable for drug delivery via controlled radical polymerization techniques. Such star polymers can be employed to release drugs within the human body in a controlled manner over time and are thus able to target specific sites, i.e. a tumor. The release characterisitics are be influenced by the structure and the size of the star polymer, which can easily be altered via controlled radical polymerization techniques. These novel stars are expected to improve the release kinetics of the drug comparing to similar structured micelles due to their higher stability upon injection.Read moreRead less
Innovative Approaches to Membrane Protein Crystallography & Drug Discovery. Membrane proteins make up around 30% of the predicted products from our human genome, are critical for life, and represent the targets of biological agents like hormones and toxins as well as most drugs. Yet these proteins have persistently defied our best efforts to study them: we know very little about what they do or what they look like. This project is aimed at cracking the problem of membrane proteins, while at the ....Innovative Approaches to Membrane Protein Crystallography & Drug Discovery. Membrane proteins make up around 30% of the predicted products from our human genome, are critical for life, and represent the targets of biological agents like hormones and toxins as well as most drugs. Yet these proteins have persistently defied our best efforts to study them: we know very little about what they do or what they look like. This project is aimed at cracking the problem of membrane proteins, while at the same time developing screening methods that can be used to design drugs against them. The long-term benefits to the community will include fundamental new knowledge and the development of new technologies and pharmaceuticals.Read moreRead less
Molecular structure and function of the glycine receptor. This proposal will employ a cutting edge approach to reveal fundamental new insights into the ways that ligand-gated ion channels, and proteins in general, work. The new knowledge and technology developed here will broaden and strengthen Australia's research expertise across a number of basic scientific disciplines. The results will also have relevance to human health. Glycine receptors have an essential role in brain function and are ....Molecular structure and function of the glycine receptor. This proposal will employ a cutting edge approach to reveal fundamental new insights into the ways that ligand-gated ion channels, and proteins in general, work. The new knowledge and technology developed here will broaden and strengthen Australia's research expertise across a number of basic scientific disciplines. The results will also have relevance to human health. Glycine receptors have an essential role in brain function and are targets for anaesthetics and drugs of abuse. GlyRs are also important in modulating pain sensation by the brain. New insights into how natural agonists and drugs affect ion channel structure and function may lead to novel therapeutic opportunities and improved drug structure predictions.Read moreRead less
Ion transport in the malaria parasite and parasitised erythrocyte. This work will contribute to the national research effort in parasitology (an area in which the ARC has established a Research Network), as well as laying the groundwork for subsequent efforts (not part of this grant) to develop new antimalarial strategies. Although not yet endemic in Australia, malaria is a serious problem in the local region and, as the major developed nation in the region Australia has an obligation to make ....Ion transport in the malaria parasite and parasitised erythrocyte. This work will contribute to the national research effort in parasitology (an area in which the ARC has established a Research Network), as well as laying the groundwork for subsequent efforts (not part of this grant) to develop new antimalarial strategies. Although not yet endemic in Australia, malaria is a serious problem in the local region and, as the major developed nation in the region Australia has an obligation to make a significant contribution to research in this area. The work proposed here will contribute to Australia's meeting this obligation.Read moreRead less
Second messenger-activated calcium channels in liver cells. This project concerns second messenger-activated calcium channels, part of the family of hormone-activated calcium channels which are essential to the functions of all animal cells. The aims are to elucidate the properties of a novel "large conductance" Ca2+ channel (using maitotoxin as an artificial activator), an inositol 1,4,5-trisphosphate-activated calcium channel, and the calcium channel formed by the transient receptor potential ....Second messenger-activated calcium channels in liver cells. This project concerns second messenger-activated calcium channels, part of the family of hormone-activated calcium channels which are essential to the functions of all animal cells. The aims are to elucidate the properties of a novel "large conductance" Ca2+ channel (using maitotoxin as an artificial activator), an inositol 1,4,5-trisphosphate-activated calcium channel, and the calcium channel formed by the transient receptor potential-1 (TRP-1) protein in hepatocytes. The electrophysiological properties, mechanisms of activation and intracellular trafficking of the channels will be investigated. It is anticipated the results will provide basic information on the physiological functions of second messenger-activated calcium channels. This will benefit the understanding of liver function, hepatotoxicity in animals, animal production and the development of pharmaceuticals in animal husbandary.Read moreRead less
Amino acid transporters and the chloroquine resistance transporter of the intracellular malaria parasite. This work entails an ongoing collaboration between three independent research groups with highly complementary expertise and experience. It will make a significant contribution to the maintenance of Australia's scientific capabilities and training opportunities. The project will yield important insights into the biology of the causative agent of a major human disease, and the mechanism by ....Amino acid transporters and the chloroquine resistance transporter of the intracellular malaria parasite. This work entails an ongoing collaboration between three independent research groups with highly complementary expertise and experience. It will make a significant contribution to the maintenance of Australia's scientific capabilities and training opportunities. The project will yield important insights into the biology of the causative agent of a major human disease, and the mechanism by which the malaria parasite has developed resistance to antimalarial drugs. Although not yet endemic in Australia, malaria is a serious problem in the local region and this work will help Australia meet its obligations to carry out high-quality research that advances our knowledge in this area.
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Cell biology of gastric acid secretion. This research will result in a better understanding of the membrane structures in cells. In turn, this information could be exploited to manipulate ion transport, uptake, secretion of biological molecules, signal transduction events and the delivery and uptake of drugs in a number of disease situations thus leading to more effective therapies.
Furthermore, this work will utilise and develop state-of-the-art technologies, contributing to national competiti ....Cell biology of gastric acid secretion. This research will result in a better understanding of the membrane structures in cells. In turn, this information could be exploited to manipulate ion transport, uptake, secretion of biological molecules, signal transduction events and the delivery and uptake of drugs in a number of disease situations thus leading to more effective therapies.
Furthermore, this work will utilise and develop state-of-the-art technologies, contributing to national competitiveness in this area. A number of students and postdoctoral fellows will be trained as a consequence of working on this project
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Activation of Tissue Factor by a Disulphide-Bond Switch. This project will define the molecular mechanism of activation of tissue factor, the initiator of blood coagulation, and design and test novel antibody therapeutics that block this activation. The applicant suggests that tissue factor is activated by a disulphide-bond switch. Should this hypothesis prove correct it would be the first example of activation of a mammalian protein by this means and, moreover, would be very amenable to therape ....Activation of Tissue Factor by a Disulphide-Bond Switch. This project will define the molecular mechanism of activation of tissue factor, the initiator of blood coagulation, and design and test novel antibody therapeutics that block this activation. The applicant suggests that tissue factor is activated by a disulphide-bond switch. Should this hypothesis prove correct it would be the first example of activation of a mammalian protein by this means and, moreover, would be very amenable to therapeutic intervention because activation occurs on the membrane surface inside blood vessels. Tissue factor activation and thrombus formation is the precipitating event in acute myocardial infarction, unstable angina and ischemic stroke, which are responsible for the majority of deaths in Australia.Read moreRead less
ION CHANNELS FORMED BY SMALL PROTEINS FROM VIRUSES. Movements of ions across cell membranes through protein ion channels are essential for normal cell function. We have found that some small proteins from viruses can form ion channels. Studying these simple channels should give us clues about the function of more complex channels, such as those in the brain, as well as giving us information about the viruses themselves. We will test whether a small protein from Ross River virus forms ion channel ....ION CHANNELS FORMED BY SMALL PROTEINS FROM VIRUSES. Movements of ions across cell membranes through protein ion channels are essential for normal cell function. We have found that some small proteins from viruses can form ion channels. Studying these simple channels should give us clues about the function of more complex channels, such as those in the brain, as well as giving us information about the viruses themselves. We will test whether a small protein from Ross River virus forms ion channels and will also test the effects of selected mutations in proteins from influenza and AIDS viruses that we have shown previously to form ion channels.Read moreRead less
Diversity and Defence: Characterisation of Extremely Variable Defensive Proteins from Sea Urchins. Antibiotic resistance is a global problem. In this project, we will study a new class of potential antibiotics - purpuratins - from sea urchins. Purpuratins are unique when compared to other antimicrobials because of their extreme structural diversity. By investigating that diversity, we will shed new light on biological methods for targeted drug design. This information will be critical to the de ....Diversity and Defence: Characterisation of Extremely Variable Defensive Proteins from Sea Urchins. Antibiotic resistance is a global problem. In this project, we will study a new class of potential antibiotics - purpuratins - from sea urchins. Purpuratins are unique when compared to other antimicrobials because of their extreme structural diversity. By investigating that diversity, we will shed new light on biological methods for targeted drug design. This information will be critical to the development of tailor-made antibiotics that are fine-tuned to kill particular micro-organisms. Our work represents a collaboration between researchers in Australia and the United States. It contributes directly to international scientific co-operation whilst providing high level training for young Australian researchers and students. Read moreRead less