A unified approach to studies on mitochondrial biogenesis. Mitochondria supply the cell with the majority of its energy as well as performing other key functions. How mitochondrial processes are regulated within the cell is an important area of biology. The broad aims of this collaboration are to analyse processes involved in mitochondrial biogenesis using yeast and mammalian cells as model systems. In particular the protein import processes and mitochondrial stress responses will be studied. Th ....A unified approach to studies on mitochondrial biogenesis. Mitochondria supply the cell with the majority of its energy as well as performing other key functions. How mitochondrial processes are regulated within the cell is an important area of biology. The broad aims of this collaboration are to analyse processes involved in mitochondrial biogenesis using yeast and mammalian cells as model systems. In particular the protein import processes and mitochondrial stress responses will be studied. The outcomes of this work will enable us to gain an appreciation of the similarities and differences in processes that exist between organisms so that general, unifying models can be made.Read moreRead less
New inhibitors of HIV based on cellular enzymes. Over 39 million people are infected with HIV worldwide. However, none of the most highly affected countries have yet reached the peak in AIDS-related illness and death, thus the global impact of HIV/AIDS will get significantly worse, before it gets better.
In Australia, HIV is again on the rise. Ironically, improved treatments that have extended life expectancy will cause the number of HIV infected Australians to rise for many years to come. ....New inhibitors of HIV based on cellular enzymes. Over 39 million people are infected with HIV worldwide. However, none of the most highly affected countries have yet reached the peak in AIDS-related illness and death, thus the global impact of HIV/AIDS will get significantly worse, before it gets better.
In Australia, HIV is again on the rise. Ironically, improved treatments that have extended life expectancy will cause the number of HIV infected Australians to rise for many years to come. Therefore many Australians will suffer from the combined impact of the AIDS illness itself, opportunistic infections, the side-effects of treatment and natural aging. We aim to develop new drugs to combat this disease to help people everywhere lead happier, healthier and more productive lives.Read moreRead less
Sensing atmosphere: Understanding the HNOX-protein gas-sensing capability and how it is affected by heme-oxidation. The project investigates how gas sensing heme-proteins from the novel HNOX (Heme-Nitric Oxide) family are able to discriminate between different gaseous ligands such as O2 and NO and how oxidation of the heme alters this response. The gas-sensing capability of the HNOX proteins is crucial for organisms ranging from bacteria to humans. Thus, understanding of these signalling mechani ....Sensing atmosphere: Understanding the HNOX-protein gas-sensing capability and how it is affected by heme-oxidation. The project investigates how gas sensing heme-proteins from the novel HNOX (Heme-Nitric Oxide) family are able to discriminate between different gaseous ligands such as O2 and NO and how oxidation of the heme alters this response. The gas-sensing capability of the HNOX proteins is crucial for organisms ranging from bacteria to humans. Thus, understanding of these signalling mechanisms will have a strong impact on many scientific fields from the control of pathogen growth to human blood pressure regulation. This collaboration will establish Australian scientists and as world-leading in the field of NO and redox signalling. This development will also be of substantial benefit for the training of the next generation of Australian students and scientists.Read moreRead less
Structure and function of novel transporters in alphaproteobacteria. First, detailed knowledge of a set of membrane transporters and the way their activity might be inhibited, will have implications for the treatment of human disease. Second, excellent outcomes are provided for the training of postgraduate students and research staff. This project entails cutting edge technology, and the transfer of technical capabilities not currently available in Australia. Third, our studies on non-pathogenic ....Structure and function of novel transporters in alphaproteobacteria. First, detailed knowledge of a set of membrane transporters and the way their activity might be inhibited, will have implications for the treatment of human disease. Second, excellent outcomes are provided for the training of postgraduate students and research staff. This project entails cutting edge technology, and the transfer of technical capabilities not currently available in Australia. Third, our studies on non-pathogenic species of alpha-proteobacteria provides for a timely advance in our knowledge of their biology: other species of alpha-proteobacteria were amongst the first organisms trialled for biological weapons by the USA and the former Soviet Union, and those pathogenic species are rated as Class 3 organisms.Read moreRead less
Role of autophagy in degradation of endoplasmic reticulum (ER)-localised protein aggregates. This study will provide a new understanding of protein aggregate accumulation in the endoplasmic reticulum (ER), a phenomenon that occurs in aging cells and protein conformational diseases, and under stress conditions and during secretory protein overexpression. This information will inform strategies to prevent the onset of protein conformational diseases and help identify targets for pharmaceutical int ....Role of autophagy in degradation of endoplasmic reticulum (ER)-localised protein aggregates. This study will provide a new understanding of protein aggregate accumulation in the endoplasmic reticulum (ER), a phenomenon that occurs in aging cells and protein conformational diseases, and under stress conditions and during secretory protein overexpression. This information will inform strategies to prevent the onset of protein conformational diseases and help identify targets for pharmaceutical intervention. In addition, a powerful model system for studies of ER protein aggregation will be established, high-level training in biochemistry and morphometry will be provided, and an international collaboration of the highest calibre will be initiated.Read moreRead less
Regulation of proteolysis by specialised adaptor proteins. Training research scientists of the future forms an integral part of this research program and this collaboration will provide an excellent opportunity for young Australian scientists to be exposed to the very professional and competitive environment of basic research, as it exists in Germany. It will expose early career researchers to new ideas and emerging methodologies arming them with valuable skills, which they will transfer to Aust ....Regulation of proteolysis by specialised adaptor proteins. Training research scientists of the future forms an integral part of this research program and this collaboration will provide an excellent opportunity for young Australian scientists to be exposed to the very professional and competitive environment of basic research, as it exists in Germany. It will expose early career researchers to new ideas and emerging methodologies arming them with valuable skills, which they will transfer to Australia. The involvement of Prof. Turgay in the Deutsche Forschungsgemeinschaft (DFG) Priority Programme: Proteolysis in Prokaryotes also provides a unique opportunity for these young researchers to interact with several of the worlds leading scientists in the area of proteolysis, enhancing Australia's reputation at the forefront of science.Read moreRead less
Ubiquinone in Giardia: Amitochondrial component in an amitochondriate parasite. Giardia intestinalis is a fascinating organism, it is one of the most primitive nucleated organisms known and is responsible for ~280 million infections annually. Ubiquinone is usually associated with mitochondrial function, however it has been found in Giardia, which lacks this organelle. Our initial studies show that in Giardia, ubiquinone plays essential roles in electron transport pathways associated with membr ....Ubiquinone in Giardia: Amitochondrial component in an amitochondriate parasite. Giardia intestinalis is a fascinating organism, it is one of the most primitive nucleated organisms known and is responsible for ~280 million infections annually. Ubiquinone is usually associated with mitochondrial function, however it has been found in Giardia, which lacks this organelle. Our initial studies show that in Giardia, ubiquinone plays essential roles in electron transport pathways associated with membrane energisation and oxidative stress management. Elucidation of these mechanisms will have a major impact on the understanding of Giardia and other anaerobic organisms as well as being of significant evolutionary and medical importance.
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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
Identification of structural proteins in the tissue cyst wall of Toxoplasma gondii. Most infections with Toxoplasma gondii are asymptomatic, however, infection during pregnancy can lead to miscarriage or blindness, deafness and mental retardation in the developing baby. Furthermore, in AIDS patients, toxoplasmosis is the leading cause of fatal encephalitis as the normally dormant tissue cysts are reactivated in the absence of an effective immune system. In Australia, it has been estimated that ~ ....Identification of structural proteins in the tissue cyst wall of Toxoplasma gondii. Most infections with Toxoplasma gondii are asymptomatic, however, infection during pregnancy can lead to miscarriage or blindness, deafness and mental retardation in the developing baby. Furthermore, in AIDS patients, toxoplasmosis is the leading cause of fatal encephalitis as the normally dormant tissue cysts are reactivated in the absence of an effective immune system. In Australia, it has been estimated that ~30% of the population is infected with T. gondii and the occurrence of congenital toxoplasmosis is 0.2% of live births, which translates to roughly 500 cases/year. Our research will identify structural proteins in Toxoplasma cyst walls that will lead to the design of new strategies to control the diseases caused by these parasites.Read moreRead less
The effects of alpha-2-macroglobulin on amyloid formation and toxicity. The expected outcomes will provide major advances in understanding how the abundant human blood protein alpha-2-macroglobulin influences the formation of protein aggregates that underpin a number of serious diseases (e.g. Alzheimer's disease). The linkages involved are of the highest calibre and will give the Fellowship holder a unique opportunity for training in environments that are truly internationally leading-edge. Fur ....The effects of alpha-2-macroglobulin on amyloid formation and toxicity. The expected outcomes will provide major advances in understanding how the abundant human blood protein alpha-2-macroglobulin influences the formation of protein aggregates that underpin a number of serious diseases (e.g. Alzheimer's disease). The linkages involved are of the highest calibre and will give the Fellowship holder a unique opportunity for training in environments that are truly internationally leading-edge. Furthermore, the very high novelty and broad significance of this work indicate that it will produce high-impact publications which will tangibly assist Australia being recognized as a major contributor to international research outcomes of the highest quality.Read moreRead less