How Does NF-kB2 Regulate Thymic Selection To Prevent Organ-specific Autoimmune Disease?
Funder
National Health and Medical Research Council
Funding Amount
$787,600.00
Summary
Autoimmune diseases like type 1 diabetes and thyroiditis arise from defects that cause the immune system to confuse self and non-self. Normally, this distinction is programmed in the thymus. We recently identified the gene that causes a form of autoimmune disease. We also made an important discovery about how the thymus gland regulates self-non-self discrimination. We will build on these two discoveries to gain a precise understanding of how the immune system normally avoids autoimmune disease.
Modeling Human Actin Related Protein 2/3 Complex Subunit 1B (ARPC1B) Deficiency In Mice
Funder
National Health and Medical Research Council
Funding Amount
$755,005.00
Summary
The actin cytoskeleton forms the structure that not only keeps cells in their normal shape but is also essential for the movement of cells and for interaction between cells. We have recently identified the first patients with an immunodeficiency caused by a defect in a gene called ARPC1B, which plays a crucial role in the regulation of actin. Through the investigation of novel mouse models we will elucidate the pathomechanism underlying the disease of these patients.
Physiological and molecular controls of plant transpiration efficiency: investigating the role of the ERECTA gene. Water is the single most limiting factor in agriculture and the world's supply of fresh water is diminishing, the greatest fraction of total water use being by agriculture. Progress in water-use efficiency will have social value, and this program should help us to achieve it. Our progress in this area is already one of the most successful of 'bottom-up' approaches - in the sense of ....Physiological and molecular controls of plant transpiration efficiency: investigating the role of the ERECTA gene. Water is the single most limiting factor in agriculture and the world's supply of fresh water is diminishing, the greatest fraction of total water use being by agriculture. Progress in water-use efficiency will have social value, and this program should help us to achieve it. Our progress in this area is already one of the most successful of 'bottom-up' approaches - in the sense of transferring knowledge from biochemistry and biophysics to breeding and agronomy, as CSIRO now has a successful wheat breeding program based on this earlier work of ours. Now that we have discovered a gene that controls water-use efficiency at the leaf level, we wish to see how the gene works, and how it affects mineral nutrition of leaves.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
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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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
Structural Determinants of an Intracellular Calcium Store. Understanding the molecular interactions between key proteins in calcium signalling in muscle and the heart will allow calcium signalling to be used as a platform for a variety of purposes. These include reducing the debilitating effects of changes in calcium signalling and muscle performance in aging and in genetically- or drug-induced disorders. The project will have benefits for Australian biotechnology since it will facilitate the de ....Structural Determinants of an Intracellular Calcium Store. Understanding the molecular interactions between key proteins in calcium signalling in muscle and the heart will allow calcium signalling to be used as a platform for a variety of purposes. These include reducing the debilitating effects of changes in calcium signalling and muscle performance in aging and in genetically- or drug-induced disorders. The project will have benefits for Australian biotechnology since it will facilitate the design of novel compounds for treating muscle disorders in animals and humans, for improving meat quality and for use as insecticides. The project will facilitate graduate and undergraduate training in basic science with exposure to biotechnology, through our commercial partner Biotron.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
It is feasible to sequence patient genomes but we need to know more about how genetic variants cause complex disease. We have sequenced genomes from patients with immune deficiency and will test the idea that genetic variation causes consistent changes in particular white blood cells, thus providing a bridge between genomic information and clinical diagnosis. Outcomes will include more accurate diagnosis, better understanding of immunity, and a strategy for using whole genome information.