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
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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: 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
Malarial parasite surface proteins: structure and interactions of key merozoite antigens. Malaria remains one the most lethal infectious diseases in the world today, being directly responsible for around 2 million deaths annually, many in children under 5 years of age. Related parasitic diseases affect livestock in malaria-endemic regions and more broadly. There is an urgent need for an improved understanding of how these parasites invade target red blood cells. Knowing the structures of key pro ....Malarial parasite surface proteins: structure and interactions of key merozoite antigens. Malaria remains one the most lethal infectious diseases in the world today, being directly responsible for around 2 million deaths annually, many in children under 5 years of age. Related parasitic diseases affect livestock in malaria-endemic regions and more broadly. There is an urgent need for an improved understanding of how these parasites invade target red blood cells. Knowing the structures of key proteins on the parasite cell surface will provide a deeper understanding of host-parasite interactions, as well as a basis for the design of vaccines or drugs that interfere with parasite invasion of host red blood cells. Read moreRead less
The roles of novel pathways in the activation and regulation of the adaptive immune response in health and disease. The immune system is designed to protect us against infection and vaccines exploit this with great success in preventing many infections. However, the immune system can also 'fail' and attack the body in a process called autoimmunity e.g. destroying joints in rheumatoid arthritis. This proposal will define how white blood cells work to make better vaccines against infection and ho ....The roles of novel pathways in the activation and regulation of the adaptive immune response in health and disease. The immune system is designed to protect us against infection and vaccines exploit this with great success in preventing many infections. However, the immune system can also 'fail' and attack the body in a process called autoimmunity e.g. destroying joints in rheumatoid arthritis. This proposal will define how white blood cells work to make better vaccines against infection and how these same immune cells can malfunction to create autoimmune diseases like Crohn's disease.Read moreRead less
The Production of Respiratory Cell Lineages from Human Embryonic Stem Cells: Towards a Cell Replacement Therapy for the Treatment of Respiratory Specific Deficits. Embryonic stem (ES) cells are a primitive embryonic cell type that can be maintained and grown in vitro. Mouse ES cells can be instructed to develop into a wide range of specific adult cell types. Research into human ES cells has more recently commenced and has already resulted in the controlled production of specific nerve cells by o ....The Production of Respiratory Cell Lineages from Human Embryonic Stem Cells: Towards a Cell Replacement Therapy for the Treatment of Respiratory Specific Deficits. Embryonic stem (ES) cells are a primitive embryonic cell type that can be maintained and grown in vitro. Mouse ES cells can be instructed to develop into a wide range of specific adult cell types. Research into human ES cells has more recently commenced and has already resulted in the controlled production of specific nerve cells by our group. The following project aims to create respiratory lineages from both mouse and human ES cells. Such an undertaking thus aims to provide a basis for the treatment of respiratory specific diseases such as cystic fibrosis and emphysema.Read moreRead less