Post Transcriptional Regulation Of Plasminogen Activator Inhibitor Type 2 Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$318,000.00
Summary
The process of wound healing, cell migration and the spread of cancers requires the recruitment of specialised proteases to the cell surface . These proteases act to degrade other proteins, mainly in the extracellular space, which in turn allows cells to move around, wounds to close, and blood clots to disappear. The plasminogen activating system is one of the enzyme systems involved in these events. One of the proteases that cleaves plasminogen to its active form, plasmin, is urokinase (u-PA) a ....The process of wound healing, cell migration and the spread of cancers requires the recruitment of specialised proteases to the cell surface . These proteases act to degrade other proteins, mainly in the extracellular space, which in turn allows cells to move around, wounds to close, and blood clots to disappear. The plasminogen activating system is one of the enzyme systems involved in these events. One of the proteases that cleaves plasminogen to its active form, plasmin, is urokinase (u-PA) and the activity of u-PA is regulated by its natural inhibitor called plasminogen activator inhibitor type 2 (PAI-2). u-PA is strongly implicated in the progression of metastatic cancer and high levels of PAI-2 relative to u-PA is regularly seen as a positive prognostic indicator for metastatic cancer. In this situation, PAI-2 acts to limit the activity of u-PA thereby restricting the migration potential of the cancer. PAI-2 is unusual because it exists both inside and outside the cell. Outside the cell, PAI-2 acts to inhibit u-PA activity, while inside the cell, PAI-2 also plays a role in the inhibition of cell growth and differentiation. It is therefore important to understand how the production of PAI-2 is regulated in cells. A significant component of PAI-2 regulation occurs post-transcriptionally, particularly at the level of mRNA stability. We have identified some of the proteins that bind to PAI-2 mRNA and influence its longevity in the cell. This project aims to further undertand how these as well as other PAI-2 mRNA binding proteins influence the expression of the PAI-2 gene.Read moreRead less
Does a novel class of small RNA molecules control self-incompatibility in solanaceous plants? Self-incompatibility is a simple and genetically defined cell recognition system that prevents inbreeding in many plant species. Flowers of self-incompatible plants can distinguish self pollen from foreign pollen, and allow only foreign pollen to fertilise their egg cells. This proposal will investigate the possibility that the part of the genetic self-incompatibility locus controlling recognition of ....Does a novel class of small RNA molecules control self-incompatibility in solanaceous plants? Self-incompatibility is a simple and genetically defined cell recognition system that prevents inbreeding in many plant species. Flowers of self-incompatible plants can distinguish self pollen from foreign pollen, and allow only foreign pollen to fertilise their egg cells. This proposal will investigate the possibility that the part of the genetic self-incompatibility locus controlling recognition of pollen is a novel type of gene that encodes a small RNA molecule but no protein. Knowledge gained by studying the self-incompatibility genes will help us to understand how plant cells recognise each other, and may allow us to manipulate seed (and hence crop) production.Read moreRead less
The Role of High-Frequency Antigenic Variation in The Pathogenesis of Mycoplasma infection. The main goal of the proposed project is to understand the molecular mechanisms of phase/antigenic variation and its effects on mycoplasma pathogenesis. In this context I will use the well-characterised Mycoplasma synoviae haemagglutinin, MSPA, to establish the role of its phase-variable expression in the type and extent of M. synoviae disease. Additionally, the relationship between MSPA phase variation a ....The Role of High-Frequency Antigenic Variation in The Pathogenesis of Mycoplasma infection. The main goal of the proposed project is to understand the molecular mechanisms of phase/antigenic variation and its effects on mycoplasma pathogenesis. In this context I will use the well-characterised Mycoplasma synoviae haemagglutinin, MSPA, to establish the role of its phase-variable expression in the type and extent of M. synoviae disease. Additionally, the relationship between MSPA phase variation and gene rearrangements in the MSPB-encoding gene will be elucidated. The results will contribute to our understanding of the pathogenesis of bacterial disease and of the evolution of pathogenic mechanisms in bacterial pathogens.Read moreRead less
New approaches for screening cereal germplasm for enhanced microbial pathogen resistance and desirable grain texture. The trait of grain hardness (texture) is of significance to the Australian infrastructure, as exports of hard wheat contribute over 5 billion dollars per year on average to the national economy and hard wheats are also important for domestic usage. The genes responsible for grain texture also impart resistance to bacterial and fungal pathogens which can cause extensive damage. ....New approaches for screening cereal germplasm for enhanced microbial pathogen resistance and desirable grain texture. The trait of grain hardness (texture) is of significance to the Australian infrastructure, as exports of hard wheat contribute over 5 billion dollars per year on average to the national economy and hard wheats are also important for domestic usage. The genes responsible for grain texture also impart resistance to bacterial and fungal pathogens which can cause extensive damage. However, the Australian gene pool has very limited genetic diversity in grain textures and thus possibly in pathogen resistance. The project will work out the science behind these two traits and identify lines with new variants of textures and pathogen resistances, thus greatly benefiting the national infrastructure and local primary industries.Read moreRead less
Regulation of Cellulose Biosynthesis in Commercially Important Cereal Crop Species. The long term strategic research alliance with DuPont Pioneer will lead to the development of breakthrough science in emerging technologies that are relevant: a) to agricultural production, b) to human health and c) to renewable bio-fuel production from crop residues. The alliance will attract significant international investment in Australian research and foster an intellectual environment for world-class resear ....Regulation of Cellulose Biosynthesis in Commercially Important Cereal Crop Species. The long term strategic research alliance with DuPont Pioneer will lead to the development of breakthrough science in emerging technologies that are relevant: a) to agricultural production, b) to human health and c) to renewable bio-fuel production from crop residues. The alliance will attract significant international investment in Australian research and foster an intellectual environment for world-class research training of postgraduate students and postdoctoral scientists, in both a higher education and an industry context.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0454052
Funder
Australian Research Council
Funding Amount
$733,595.00
Summary
Tandem Matrix-Assisted Laser Desorption/Ionisation Time-Of-Flight Mass Spectrometer and Robots for High Throughput Proteomics Analysis. This proposal seeks to establish the capacity to perform high-energy tandem mass spectrometry on a high throughput basis, through purchase and coordinated operation of a Matrix-Assisted Laser Desorption/Ionisation - Time of Flight / Time of Flight - Mass Spectrometer and ancillary equipment, to enhance the proteomics expertise, infrastructure and research plans ....Tandem Matrix-Assisted Laser Desorption/Ionisation Time-Of-Flight Mass Spectrometer and Robots for High Throughput Proteomics Analysis. This proposal seeks to establish the capacity to perform high-energy tandem mass spectrometry on a high throughput basis, through purchase and coordinated operation of a Matrix-Assisted Laser Desorption/Ionisation - Time of Flight / Time of Flight - Mass Spectrometer and ancillary equipment, to enhance the proteomics expertise, infrastructure and research plans of a network of institutions from Queensland and New South Wales and their collaborators. Access to such instrumentation is critical to high level achievement in proteomics, a key platform technology for National Research Priorities relating to Frontier Technologies. No comparable instrument currently exists in Australia.Read moreRead less
CesA (cellulose synthase) genes of Arabidopsis; all doing the same job or specialists cooperating to make the most abundant biopolymer. The biosphere makes more cellulose than any other polymer with fibre industries depending on its physical properties and atmospheric carbon dioxide levels depending on its stability as a carbon sink. Demonstrations that cellulose production needs CesA genes drove recent progress in elucidating the mechanism of synthesis. CesA proteins all look very similar but i ....CesA (cellulose synthase) genes of Arabidopsis; all doing the same job or specialists cooperating to make the most abundant biopolymer. The biosphere makes more cellulose than any other polymer with fibre industries depending on its physical properties and atmospheric carbon dioxide levels depending on its stability as a carbon sink. Demonstrations that cellulose production needs CesA genes drove recent progress in elucidating the mechanism of synthesis. CesA proteins all look very similar but if all do the same job, why do plants need so many and why do none seem redundant? We will make gene interchanges in transgenic plants, build chimeric genes and identify where each CesA protein operates. This will identify their individual and cooperative contributions to cellulose production.Read moreRead less
Proteomic and Transcriptional Profiling of Cartilage. Gene expression and signalling pathways that regulate cartilage formation, and its orderly transition to bone, are poorly described. Our studies will, for the first time, combine two complementary cutting-edge approaches, protein identification by proteomic analysis, and mRNA profiling by microarray analysis, to define these pathways and develop a comprehensive catalogue of proteins and gene expression patterns during cartilage development a ....Proteomic and Transcriptional Profiling of Cartilage. Gene expression and signalling pathways that regulate cartilage formation, and its orderly transition to bone, are poorly described. Our studies will, for the first time, combine two complementary cutting-edge approaches, protein identification by proteomic analysis, and mRNA profiling by microarray analysis, to define these pathways and develop a comprehensive catalogue of proteins and gene expression patterns during cartilage development and bone formation. This information will provide insight into the regulation of cartilage differentiation, maturation and structure, and will provide a critical platform for the development of more sophisticated cartilage and bone biomaterials for improved tissue repair and regeneration.Read moreRead less