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
Functional genomics of large clostridial plasmids. The aims of this genomics project are to determine how large DNA elements called plasmids are able to be transferred between different strains of a bacterium that causes disease in domestic livestock. These plasmids carry genes that encode the potent protein toxins that are responsible for several diseases. To understand how these diseases are spread we must learn how the plasmids have evolved and whether they can move from bacterium to bacteriu ....Functional genomics of large clostridial plasmids. The aims of this genomics project are to determine how large DNA elements called plasmids are able to be transferred between different strains of a bacterium that causes disease in domestic livestock. These plasmids carry genes that encode the potent protein toxins that are responsible for several diseases. To understand how these diseases are spread we must learn how the plasmids have evolved and whether they can move from bacterium to bacterium. The successful completion of the project will result in a detailed understanding of genetic elements that are important mediators of several diseases of importance to Australian primary industry.Read moreRead less
Characterising post-translational modifications in bacterial proteins. This project represents the first global attempt to characterize post-translational modifications in bacterial proteins using the tools of proteomics. Modifications to proteins are key elements in altering their function. In bacteria, modifications are important in cell-cell adhesion, signalling and triggering of the immune response. Characterisation of modified proteins and their sites of modification represents an opportuni ....Characterising post-translational modifications in bacterial proteins. This project represents the first global attempt to characterize post-translational modifications in bacterial proteins using the tools of proteomics. Modifications to proteins are key elements in altering their function. In bacteria, modifications are important in cell-cell adhesion, signalling and triggering of the immune response. Characterisation of modified proteins and their sites of modification represents an opportunity to understand how bacterial cell populations communicate in the environment, as well as aid in understanding pathogenesis in medical, veterinary and food-borne pathogens. Therefore, improved vaccine targets and therapeutics, as well as method-based products, may be generated by this project.Read moreRead less
Functional Genomics and Host Cell Specificity of Herpesviruses. Herpesviruses cause severe diseases in many species, but research on their large DNA genomes has been difficult due to the need to use animal cell cultures for the generation of virus mutants. The cloning of complete herpesvirus genomes as Bacterial Artificial Chromosomes (BACs) has revolutionized herpesvirus genomics, and it is now possible to examine herpesvirus gene functions in unprecedented detail using elegant new mutation tec ....Functional Genomics and Host Cell Specificity of Herpesviruses. Herpesviruses cause severe diseases in many species, but research on their large DNA genomes has been difficult due to the need to use animal cell cultures for the generation of virus mutants. The cloning of complete herpesvirus genomes as Bacterial Artificial Chromosomes (BACs) has revolutionized herpesvirus genomics, and it is now possible to examine herpesvirus gene functions in unprecedented detail using elegant new mutation techniques. The project, based on two related equine herpesviruses, will identify new targets for antiviral drugs or vaccines. These herpesvirus BAC systems represent frontier science that greatly facilitates the study of links between genome and phenome.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
Multiplexed Molecular Reading of Protein Associations via Nanoscaled Devices. Current developments in Nanoscience and Nanotechnology hold many promises in terms of revolutionising our industrial base, transforming biology, medical science and practice. This project strives to achieve some of these goals by, for the first time, building and testing nano-scaled devices with the capability to rapidly ?read? information about complex protein associations. With the recent completion of the Human Ge ....Multiplexed Molecular Reading of Protein Associations via Nanoscaled Devices. Current developments in Nanoscience and Nanotechnology hold many promises in terms of revolutionising our industrial base, transforming biology, medical science and practice. This project strives to achieve some of these goals by, for the first time, building and testing nano-scaled devices with the capability to rapidly ?read? information about complex protein associations. With the recent completion of the Human Genome project, major opportunities exist to provide spectacular advances in human health care (eg, via novel diagnostics) provided that appropriate high-throughput biological reading devices can be developed. In developing such devices, this project also aims to catalyse the Australian Nanotechnology/Biotechnology industry.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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Intrinsically Unstructured Proteins (IUPs): NMR characterization, prediction, and application to malarial proteome. Determination of protein structures with longer DR by NMR will enrich the DR dataset and provide a deeper understanding of protein structure-function relationships and protein folding pathways. The proposal will also provide valuable information in the key applied area of target selection in structural biology. Not all current web services are freely accessible and available servi ....Intrinsically Unstructured Proteins (IUPs): NMR characterization, prediction, and application to malarial proteome. Determination of protein structures with longer DR by NMR will enrich the DR dataset and provide a deeper understanding of protein structure-function relationships and protein folding pathways. The proposal will also provide valuable information in the key applied area of target selection in structural biology. Not all current web services are freely accessible and available services can be improved further by using more reliable training dataset or more effective algorithms, development of a national DR predictor will help Australian structural biologists increase the success rate of structure determination and provide greater insight into a range of proteomes.Read moreRead less