Molecular basis of the antifungal and antimalarial activity of a plant defensin. The plant defensin NaD1 has potent inhibitory activity against a number of agronomically important fungal pathogens. These species are major pathogens of cotton and other important agricultural crops such as canola and potatoes. These pathogens cause serious economic losses and threaten the future of the cotton industry in Australia. NaD1 also has potential as a new antibiotic for treatment of infections in human ....Molecular basis of the antifungal and antimalarial activity of a plant defensin. The plant defensin NaD1 has potent inhibitory activity against a number of agronomically important fungal pathogens. These species are major pathogens of cotton and other important agricultural crops such as canola and potatoes. These pathogens cause serious economic losses and threaten the future of the cotton industry in Australia. NaD1 also has potential as a new antibiotic for treatment of infections in humans.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.
Read moreRead less
Oxidative stress-induced alterations of the host erythrocyte by the malaria parasite. The malaria parasite spends part of its lifecycle inside the red blood cells of its host. During this time, the parasite modifies many of the features of the red blood cell and subjects it to high levels of oxidative stress. We will use and develop a variety of fluorescence and microscopic techniques to understand the molecular basis of the alterations in the organization of membrane proteins in malaria parasit ....Oxidative stress-induced alterations of the host erythrocyte by the malaria parasite. The malaria parasite spends part of its lifecycle inside the red blood cells of its host. During this time, the parasite modifies many of the features of the red blood cell and subjects it to high levels of oxidative stress. We will use and develop a variety of fluorescence and microscopic techniques to understand the molecular basis of the alterations in the organization of membrane proteins in malaria parasite-infected red blood cells. We will examine the roles of oxidative stress and of parasite proteins in modulating the properties of the host cell membrane.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
Monolayer crystallization of membrane proteins. Membrane proteins comprise 25-40% of all proteins and conduct a myriad of finely tuned reactions in every cell. Despite their importance and diversity only ~40 membrane protein structures have been solved, due to the difficulty of producing high quality 2D and 3D crystals. We propose to develop and use the new monolayer crystallization technique, which employs a lipid monolayer as a crystallization template for 2D crystal production. A number of ....Monolayer crystallization of membrane proteins. Membrane proteins comprise 25-40% of all proteins and conduct a myriad of finely tuned reactions in every cell. Despite their importance and diversity only ~40 membrane protein structures have been solved, due to the difficulty of producing high quality 2D and 3D crystals. We propose to develop and use the new monolayer crystallization technique, which employs a lipid monolayer as a crystallization template for 2D crystal production. A number of important membrane proteins are available for these structural studies including ABC transporters, Caveolin-3 and the NS1 protein of Dengue virus, all of which are difficult to crystallize using conventional techniques.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
Control of cell survival by the Bcl-2 protein family. The control of apoptosis is essential for homeostasis. It is now realized that deregulation of apoptosis is a hallmark of many cancers. In apoptosis, the Bcl-2 protein family plays a central role in determining if a cell lives or dies. My proposal aim is to provide a deeper understanding of how cell death and survival is controlled by the Bcl-2 family. These studies have notable implications for understanding normal cell death control as well ....Control of cell survival by the Bcl-2 protein family. The control of apoptosis is essential for homeostasis. It is now realized that deregulation of apoptosis is a hallmark of many cancers. In apoptosis, the Bcl-2 protein family plays a central role in determining if a cell lives or dies. My proposal aim is to provide a deeper understanding of how cell death and survival is controlled by the Bcl-2 family. These studies have notable implications for understanding normal cell death control as well as aid in the development of therapeutic agents such as ones to overcome the resistance to apoptosis, found in many types of cancer.Read moreRead less
Apoptotic signalling in virally infected and normal cells. Viral diseases contribute substantially to mortality and morbidity, in Australia and internationally. Emerging viral diseases, including H5N1 avian influenza, have the potential to severely impact on human health and the global economy. Concerns also exist that viruses may be used as bioweapons. This project seeks to define the mechanisms by which cell death occurs and is regulated in healthy cells, and how this is altered in virally inf ....Apoptotic signalling in virally infected and normal cells. Viral diseases contribute substantially to mortality and morbidity, in Australia and internationally. Emerging viral diseases, including H5N1 avian influenza, have the potential to severely impact on human health and the global economy. Concerns also exist that viruses may be used as bioweapons. This project seeks to define the mechanisms by which cell death occurs and is regulated in healthy cells, and how this is altered in virally infected or oncogenically transformed cells. Outcomes of this work may contribute to development of novel anti-cancer and anti-viral therapies, diagnostic reagents and vaccines.Read moreRead less
Biogenesis of red blood cell membrane modifications by the malaria parasite Plasmodium falciparum. Malaria is not only a major global health problem, but also affects countries neighbouring Australia like Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (aid and military personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology to identi ....Biogenesis of red blood cell membrane modifications by the malaria parasite Plasmodium falciparum. Malaria is not only a major global health problem, but also affects countries neighbouring Australia like Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (aid and military 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 Plasmodium falciparum infection. Developing novel targets is mandated by humanity, but also to safeguard Australia's region against the social and economic implications of this disease. An Australian developed intervention would increase the global visibility of its science, leading to increased investments.Read moreRead less