The role of neutral amino acid transport in normal physiology. Future benefits of these studies include the Promotion and Maintenance of Good Health achieved by providing: (1) a better understanding of brain and balance disorders; (2) insights into the damaging effects of the sun and; (3) existing neonatal screening programmes for Hartnup disorder with greater scientific foundation regarding the implications of inheriting this condition, including dietary advce. We will be able to provide Austr ....The role of neutral amino acid transport in normal physiology. Future benefits of these studies include the Promotion and Maintenance of Good Health achieved by providing: (1) a better understanding of brain and balance disorders; (2) insights into the damaging effects of the sun and; (3) existing neonatal screening programmes for Hartnup disorder with greater scientific foundation regarding the implications of inheriting this condition, including dietary advce. We will be able to provide Australians who inherit Hartnup disorder with a better understanding of this disease by enabling individuals and families to make choices that lead to healthy, productive and fulfilling lives.Read moreRead less
Mechanism of higher-order chromatin formation and its role in controlling gene expression. The organization of genomic DNA into chromatin has solved one of the most difficult engineering problems required for the development of a multicellular organism; the compaction of over two meters DNA into a cell almost one millionth this size. Importantly, this compaction of the genome into chromatin has also been exploited by the cell to regulate the expression of genes. The aim of this investigation is ....Mechanism of higher-order chromatin formation and its role in controlling gene expression. The organization of genomic DNA into chromatin has solved one of the most difficult engineering problems required for the development of a multicellular organism; the compaction of over two meters DNA into a cell almost one millionth this size. Importantly, this compaction of the genome into chromatin has also been exploited by the cell to regulate the expression of genes. The aim of this investigation is to elucidate how genes are assembled into complex active or inactive chromatin structures by employing a novel in vitro system. This information will have important implications for gene therapy strategies.
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The Dynamic Control of Chromatin Structure. A human chromosome is a highly heterogeneous global structure because along its axis, it folds to different extents to form either highly compacted domains that repress the expression of genes or less condensed regions that enable genes to be turned on. Changes to the structure or stability of chromosomes, and the corresponding alterations to gene expression, have been linked to many diseases states like defects in human development and cancer. This s ....The Dynamic Control of Chromatin Structure. A human chromosome is a highly heterogeneous global structure because along its axis, it folds to different extents to form either highly compacted domains that repress the expression of genes or less condensed regions that enable genes to be turned on. Changes to the structure or stability of chromosomes, and the corresponding alterations to gene expression, have been linked to many diseases states like defects in human development and cancer. This study will uncover the underpinning mechanism of how our chromosomes are organised into distinct functional domains, which may offer the potential to develop new strategies to correct chromosomal abnormalities.
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Phasevarions of Haemophilus influenzae: mechanisms and origins of a novel epigenetic system controlling coordinated random switching in expression of multiple genes. Central to the utilisation of biological information is our ability to identify and interpret DNA sequence information from genomes. In bacteria that cause disease, these investigations can identify key aspects of the infectious process or potential components of vaccines or new targets for antibiotics. Our recent work has identifie ....Phasevarions of Haemophilus influenzae: mechanisms and origins of a novel epigenetic system controlling coordinated random switching in expression of multiple genes. Central to the utilisation of biological information is our ability to identify and interpret DNA sequence information from genomes. In bacteria that cause disease, these investigations can identify key aspects of the infectious process or potential components of vaccines or new targets for antibiotics. Our recent work has identified a new genetic system, the 'phasevarion', that mediates random expression of multiple genes. The proposed research aims to advance our understanding of gene expression at the most basic level, revealing how bacteria generate diverse populations to evade environmental and immune stresses, and facilitating improved interpretation and use of DNA sequences for researchers and industry in this field.Read moreRead less
Mammalian chitinases and gene therapy: new weapons to combat fungal and insect attack in mammals. Plants combat fungal and insect attack by producing chitin degrading enzymes. Related, chitinolytic enzymes have been identified in mammals, but their functions are unclear. We found that chitinases from human macrophages inhibited fungal growth. We hypothesise that, like plants, mammalian chitinases are produced to fight chitin containing pathogens. We will transform cells with a chitotriosidase ge ....Mammalian chitinases and gene therapy: new weapons to combat fungal and insect attack in mammals. Plants combat fungal and insect attack by producing chitin degrading enzymes. Related, chitinolytic enzymes have been identified in mammals, but their functions are unclear. We found that chitinases from human macrophages inhibited fungal growth. We hypothesise that, like plants, mammalian chitinases are produced to fight chitin containing pathogens. We will transform cells with a chitotriosidase gene and encapsulate them, creating bioreactors secreting chitinases. Therapeutic effects will be tested by grafting bioreactors to mice inoculated with Aspergillus. The research is a new approach to fighting chitin containing pathogens, with potential applications from parasite infestations in livestock to fungal infections in humans.Read moreRead less
Novel Hybrid Inorganic Nanoparticles for Effective siRNA Delivery to Neurons. This project will lead to a more efficient and reliable drug delivery system to treat Huntington's disease. The insights and technology gained from this project will be directly applicable for many human diseases, both within and outside the central nervous system. This project will make a major contribution to the ARC's goal of maintaining good health and promises to significantly reduce the financial and psychologica ....Novel Hybrid Inorganic Nanoparticles for Effective siRNA Delivery to Neurons. This project will lead to a more efficient and reliable drug delivery system to treat Huntington's disease. The insights and technology gained from this project will be directly applicable for many human diseases, both within and outside the central nervous system. This project will make a major contribution to the ARC's goal of maintaining good health and promises to significantly reduce the financial and psychological burdens to patients' family and community. This project will encourage inter-disciplinary approaches to research and train highly skilled researchers both in neuroscience and nanobiotechnology to advance Australia's industrial competitiveness.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
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
Pre-clinical evaluation of snake venom proteins with therapeutic potential. Australia harbors some of the most toxic snakes in the world. Their venoms contain a range of substances that are designed to rapidly immobilize and kill their prey. These include agents that lead to enhanced blood clotting; excess bleeding. We have isolated and characterized a large number of the components involved over the last several years. The aim here is to carry out pre-clinical trials in animal models to test th ....Pre-clinical evaluation of snake venom proteins with therapeutic potential. Australia harbors some of the most toxic snakes in the world. Their venoms contain a range of substances that are designed to rapidly immobilize and kill their prey. These include agents that lead to enhanced blood clotting; excess bleeding. We have isolated and characterized a large number of the components involved over the last several years. The aim here is to carry out pre-clinical trials in animal models to test the efficacy of three proteins as anti-bleeding agents and investigate several other novel components. The ultimate outcome will be the development of novel drugs that will have application in the treatment of human disorders. 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