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Elucidating Mechanisms For The Biological Activities Of CD46.
Funder
National Health and Medical Research Council
Funding Amount
$228,000.00
Summary
The CD46 protein enables entry into cells of a number of different pathogens, including the measles virus, Neisseria meningitidis (the major cause of meningococcal disease), Neisseria gonorrhoea, Human Herpes Virus 6, and group A streptococcus. In addition, by binding to a key blood component that is often attached to foreign pathogens, CD46 can facilitate binding and entry of other pathogens. As well as facilitating entry of the pathogen, it has recently become apparent that CD46 binding trigge ....The CD46 protein enables entry into cells of a number of different pathogens, including the measles virus, Neisseria meningitidis (the major cause of meningococcal disease), Neisseria gonorrhoea, Human Herpes Virus 6, and group A streptococcus. In addition, by binding to a key blood component that is often attached to foreign pathogens, CD46 can facilitate binding and entry of other pathogens. As well as facilitating entry of the pathogen, it has recently become apparent that CD46 binding triggers a wide range of responses from the human host. Some of these responses are likely to further facilitate survival and proliferation of the pathogen, but others are more likely to facilitate host defence. For examples, signals triggered by binding to CD46 can both abrogate some aspects of the immune response (and it is though that this immunosuppression contributes to the secondary infections that cause the death of nearly one million children each year) and facilitate other aspects of the immune response. By understanding the mechanisms by which CD46 triggers these complex responses, we firstly be able to dissect how important each of these processes are to the overall pathogenecity of the virus or bacteria. Furthmore, this understanding will allow us to design better vaccines and drugs to combat these diseases.Read moreRead less
Control Of CD4 Function By Disulphide-Bond Switching
Funder
National Health and Medical Research Council
Funding Amount
$252,761.00
Summary
CD4 is a cell-surface protein that has two functions in the human body, a good one and a bad one. Its good function is as a checkpoint for development of the immune system and for response of the immune system to infection. It helps immune cells known as T cells to recognize and dispose of a foreign particle in the body. Its bad function is that it is one of two proteins that enable the HIV virus to enter and destroy immune cells. The HIV virus binds to CD4 on immune cells, which leads to fusion ....CD4 is a cell-surface protein that has two functions in the human body, a good one and a bad one. Its good function is as a checkpoint for development of the immune system and for response of the immune system to infection. It helps immune cells known as T cells to recognize and dispose of a foreign particle in the body. Its bad function is that it is one of two proteins that enable the HIV virus to enter and destroy immune cells. The HIV virus binds to CD4 on immune cells, which leads to fusion of the viral and immune cell surfaces and entry of the virus into the cell. Once inside the immune cell the virus reproduces itself and goes on to kill more immune cells. AIDS results when too many immune cells are killed. We have discovered that CD4 exists in three different forms on the immune cell surface; an oxidized, reduced or dimeric form. These different forms result from a molecular switch we discovered in CD4. We have suggested that the good and bad functions of CD4 are mediated by different forms of CD4. The good function is mediated by dimeric CD4, while the bad function is mediated by reduced CD4. The purpose of this application is to test this hypothesis. If we are correct then our findings will have significant implications for our understanding of how the immune system responds to a foreign invader and how HIV-AIDS destroys the immune system. This knowledge could be used to develop drugs that suppress the immune system when required, such as in organ transplantation, and that fight HIV-AIDS.Read moreRead less
Improving clostridial toxoid production through molecular fermentation maps. This project aims to improve vaccine production by generating detailed molecular maps of fermentation which will be used to design superior fermentation processes with reduced cost. Toxoid vaccines, used routinely in the livestock industry to prevent animal-disease caused by pathogenic Clostridia, are produced using batch fermentation processes. These processes have undergone limited optimisation over the past five deca ....Improving clostridial toxoid production through molecular fermentation maps. This project aims to improve vaccine production by generating detailed molecular maps of fermentation which will be used to design superior fermentation processes with reduced cost. Toxoid vaccines, used routinely in the livestock industry to prevent animal-disease caused by pathogenic Clostridia, are produced using batch fermentation processes. These processes have undergone limited optimisation over the past five decades. Low titres and frequent batch failures greatly affect capital use and represent a significant cost. In addition, current optimisation approaches are limited by the use of expensive and noisy endpoint assays. This project aims to use high-throughput chemistry (multi-omics) that overcome these limitations.Read moreRead less
Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastro ....Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastroenteritis. Recent statistics show that over 5 million Australians suffer from gastroenteritis each year and hospitalisation for this infection is nearly seven times higher for indigenous than non-indigenous children. Accordingly, this research has the potential to assure a healthier future for millions of Australians.Read moreRead less
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
Read moreRead less
Inhibitors of meso-diaminopimelic acid (meso-DAP) and lysine biosynthesis: targeting dihydrodipicolinate synthase. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics with novel modes of action. This project aims to generate new drug candidates that target dihydrodipicolinate synthase (DHDPS) - the first enzyme in the synthesis of the bacterial cell wall - using a triple-pronged approach. This novel approach will allow for the development of new drugs to tr ....Inhibitors of meso-diaminopimelic acid (meso-DAP) and lysine biosynthesis: targeting dihydrodipicolinate synthase. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics with novel modes of action. This project aims to generate new drug candidates that target dihydrodipicolinate synthase (DHDPS) - the first enzyme in the synthesis of the bacterial cell wall - using a triple-pronged approach. This novel approach will allow for the development of new drugs to treat a range of pathogenic bacteria, including "Golden Staph".Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0237729
Funder
Australian Research Council
Funding Amount
$735,000.00
Summary
A proteomics facility for Queensland researchers. The successful completion of sequencing of the genomes of many organisms, including man, has thrown emphasis back on the identification of proteins involved in the complex events that sustain cellular life. Our aim is to set up a world-class facility for proteomics research which will allow a large cohort of scientists at several institutions to identify individual proteins in vanishingly small samples of very complex mixtures. This facility wi ....A proteomics facility for Queensland researchers. The successful completion of sequencing of the genomes of many organisms, including man, has thrown emphasis back on the identification of proteins involved in the complex events that sustain cellular life. Our aim is to set up a world-class facility for proteomics research which will allow a large cohort of scientists at several institutions to identify individual proteins in vanishingly small samples of very complex mixtures. This facility will enable investigation of the control of gene expression, the intricate organisation of proteins within cells, and proteins which are potential drug targets. This equipment is an essential resource for Queensland research groups.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561042
Funder
Australian Research Council
Funding Amount
$852,705.00
Summary
Establishing a high-throughput Protein Production Unit. We seek to establish a world class high-throughput (H-T) protein production unit, the first of its kind in Australia. Throughout the unit robotic technology will be used to build and test protein expression systems as well as drive large scale protein production. The product of the unit will be high quality, pure protein, effective expression systems and world class research. The unit will act as a centre for research into H-T protein ex ....Establishing a high-throughput Protein Production Unit. We seek to establish a world class high-throughput (H-T) protein production unit, the first of its kind in Australia. Throughout the unit robotic technology will be used to build and test protein expression systems as well as drive large scale protein production. The product of the unit will be high quality, pure protein, effective expression systems and world class research. The unit will act as a centre for research into H-T protein expression technology, will underpin the finest biological research, provide the basis for large "structural genomic" type approaches to biological problems and provide a wealth of projects for the Australian synchrotron.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882913
Funder
Australian Research Council
Funding Amount
$300,000.00
Summary
Mass spectrometry facility for the quantitation and analysis of post-translationally modified peptides. This proposal will address a gap in our mass spectrometry capabilities and aid in our understanding of the cellular immune response and investigate the chemical diversity of the targets of immunity. This proposal has broad implications in the basic immunology of antigen presentation, in biomarker discovery as well as in the design of new vaccines in infectious disease and cancer and the develo ....Mass spectrometry facility for the quantitation and analysis of post-translationally modified peptides. This proposal will address a gap in our mass spectrometry capabilities and aid in our understanding of the cellular immune response and investigate the chemical diversity of the targets of immunity. This proposal has broad implications in the basic immunology of antigen presentation, in biomarker discovery as well as in the design of new vaccines in infectious disease and cancer and the development of therapies for autoimmune diseases. In addition to these key scientific outcomes this project will also facilitate the training of several new personnel in a skill area for which there is a critical shortage (mass spectrometry) and promote cross-disciplinary skills (immunology, biochemistry, proteomics).Read moreRead less
Biochemical, Genomic and Phenomic Analysis of Gastric Parietal Cells from Wildtype and Mutant Mice. The interface between the cell and its environment is the cell membrane. Signals, nutrients, and ions all have to cross this barrier. In addition, the cells contain many specialized intracellular membranous compartments. We know little about the signals that direct the synthesis of these structures and determine their final composition and shape. This grant will utilize acid secretory cells in the ....Biochemical, Genomic and Phenomic Analysis of Gastric Parietal Cells from Wildtype and Mutant Mice. The interface between the cell and its environment is the cell membrane. Signals, nutrients, and ions all have to cross this barrier. In addition, the cells contain many specialized intracellular membranous compartments. We know little about the signals that direct the synthesis of these structures and determine their final composition and shape. This grant will utilize acid secretory cells in the stomach to examine these questions because they contain a very extensive membrane system. We will use a state-of-the-art genetic and cell biological technologies to manipulate and analyse these cells in a whole animal setting.Read moreRead less