Conductance states of a brain glutamine transporter. Brain transporters are the target for many neuroactive drugs that are used to treat anxiety, depression and other psychotic disorders. Transport processes are also targeted to deliver neurotransmitter precursors to the brain to treat disorders such as Parkinson's disease. In this project we will study a transport process crucial for the function of neurons that release glutamate and GABA (gamma-aminobutyric acid) as neurotransmitters. The stud ....Conductance states of a brain glutamine transporter. Brain transporters are the target for many neuroactive drugs that are used to treat anxiety, depression and other psychotic disorders. Transport processes are also targeted to deliver neurotransmitter precursors to the brain to treat disorders such as Parkinson's disease. In this project we will study a transport process crucial for the function of neurons that release glutamate and GABA (gamma-aminobutyric acid) as neurotransmitters. The study of this transport process will be important for understanding disorders like epilepsy and other disorders affecting neuronal excitability.Read moreRead less
A unified model of amino acid homeostasis. This project aims to develop a unified model of amino acid homeostasis in mammalian cells and apply it to brain cells. The model will be underpinned by a mathematical algorithm that allows predicting amino acid levels in the cytosol based on fundamental parameters such as transport and metabolism. This project should provide the significant benefit of enabling the prediction of essential functions such as cell growth and survival.
Structure and function of heterodimeric amino acid transporters. Recently a new family of amino acid transporters has been identified, the members of which are involved in the delivery of amino acids between cells and tissues. All members display a rather unusual structure in that they require two subunits to be functional. The main aim of this study is to investigate the interaction between large and small subunits. The study will give insight how membrane proteins form complexes in the membran ....Structure and function of heterodimeric amino acid transporters. Recently a new family of amino acid transporters has been identified, the members of which are involved in the delivery of amino acids between cells and tissues. All members display a rather unusual structure in that they require two subunits to be functional. The main aim of this study is to investigate the interaction between large and small subunits. The study will give insight how membrane proteins form complexes in the membrane and how these interactions affect the function of a complex membrane protein.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
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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Molecular and Cellular Characterisations of the Cortical Actin Cytoskeleton in the Plant Arabidopsis thaliana. Plant cells contain extensive arrays of the cytoskeletal protein actin that attach to the plasma membrane and may play important roles in cell elongation through interactions with cortical microtubules. However, the organisation, dynamics and functions of cortical actin remain poorly understood. I will combine cell and molecular approaches to understanding cortical actin in living tissu ....Molecular and Cellular Characterisations of the Cortical Actin Cytoskeleton in the Plant Arabidopsis thaliana. Plant cells contain extensive arrays of the cytoskeletal protein actin that attach to the plasma membrane and may play important roles in cell elongation through interactions with cortical microtubules. However, the organisation, dynamics and functions of cortical actin remain poorly understood. I will combine cell and molecular approaches to understanding cortical actin in living tissue of Arabidopsis, using both wild-type and previously uncharacterised mutants, and will develop a novel mutational screening strategy to isolate mutants disrupted in plasma membrane or microtubule binding. This research will contribute significantly to a greater understanding of how the plant grows and develops.Read moreRead less
The cellulose synthase complex of the Arabidopsis primary cell wall. The polysaccharide cellulose is the basis for the wood and cotton fibre industries of Australia and much of our research on the mechanism of synthesis has been supported by those industries over the past decade. The present project focuses on the proteins making cellulose and how they organised into functional complexes that are able to make cellulose. The knowledge it provides, together with that from other projects, will move ....The cellulose synthase complex of the Arabidopsis primary cell wall. The polysaccharide cellulose is the basis for the wood and cotton fibre industries of Australia and much of our research on the mechanism of synthesis has been supported by those industries over the past decade. The present project focuses on the proteins making cellulose and how they organised into functional complexes that are able to make cellulose. The knowledge it provides, together with that from other projects, will move us towards the situation where we can manipulate the rate at which cellulose is produced and change its detailed properties. This opens the way to industry producing fibres with more desirable properties and producing novel cellulose-based materials tailored to specific applications.Read moreRead less
Gain from pain: new tools from venomous animals for exploring pain pathways. This project aims to explore animal venoms for new pain-causing toxins, to determine their structure and mechanism of action. Many venomous animals use their venom defensively and envenomation is frequently associated with rapid and often excruciating pain. In most cases the molecular mechanisms by which they achieve this is unknown. Using biochemical, pharmacological and biophysical techniques, this project expects to ....Gain from pain: new tools from venomous animals for exploring pain pathways. This project aims to explore animal venoms for new pain-causing toxins, to determine their structure and mechanism of action. Many venomous animals use their venom defensively and envenomation is frequently associated with rapid and often excruciating pain. In most cases the molecular mechanisms by which they achieve this is unknown. Using biochemical, pharmacological and biophysical techniques, this project expects to uncover toxins that employ new mechanisms of pain signalling, leading to new insights into pain physiology.Read moreRead less
Functional Genomic Analysis of Exported DNAJ Molecules in the Malaria Parasite Plasmodium falciparum. Malaria is not only a global health problem, but also affects countries surrounding Australia like PNG and Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (eg. aid and security personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology t ....Functional Genomic Analysis of Exported DNAJ Molecules in the Malaria Parasite Plasmodium falciparum. Malaria is not only a global health problem, but also affects countries surrounding Australia like PNG and Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (eg. aid and security personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology to identify new intervention targets for P. falciparum infection. Developing novel targets is mandated by humanity, and also to safeguard Australia's region against the social and economical implication of this disease. An Australian developed intervention would increase the global visibility of its science, leading to increased investments.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