Co-ordinated Action of ATM and DNA-PK in DNA damage recognition. The aim of this project is to investigate the mechanism of repair of double straind breaks in DNA sustained after radiation damage. Specifically we will focus on two proteins ATM (mutated in the genetic disorder ataxia-telangiectasia) and DNA-PK mutated in scid mice. There two proteins recognize double straind breaks in DNA and signal this damage to the DNA repair machinery of the cell and to cell cycle checkpoints. The emphasis ....Co-ordinated Action of ATM and DNA-PK in DNA damage recognition. The aim of this project is to investigate the mechanism of repair of double straind breaks in DNA sustained after radiation damage. Specifically we will focus on two proteins ATM (mutated in the genetic disorder ataxia-telangiectasia) and DNA-PK mutated in scid mice. There two proteins recognize double straind breaks in DNA and signal this damage to the DNA repair machinery of the cell and to cell cycle checkpoints. The emphasis here will be in the relationship between the two proteins in co-ordinating the repair of breaks in DNA. This information will be important in understanding mechanisms for maintaining the integrity of the genome.Read moreRead less
Investigating the role of gene loops in regulating gene expression. The ability to identify functional variants in regulatory elements will have implications for researchers in multiple fields of biology, from molecular medicine to agriculture. Transfer of expertise and application of the knowledge generated by our research to such fields stands to improve diagnosis of disease predisposition and to improve quality of animal and plant products. These outcomes will benefit all Australians. This kn ....Investigating the role of gene loops in regulating gene expression. The ability to identify functional variants in regulatory elements will have implications for researchers in multiple fields of biology, from molecular medicine to agriculture. Transfer of expertise and application of the knowledge generated by our research to such fields stands to improve diagnosis of disease predisposition and to improve quality of animal and plant products. These outcomes will benefit all Australians. This knowledge will also improve the education of Australian University students as it contributes to the development of advanced curricula and access to more powerful research methods. In addition, the project will foster important collaborations between Australian researchers and those overseas.Read moreRead less
Recombination of mitochondrial genomes: what can we learn from chigger mites? This project will bring three benefits to Australia. First, it will enhance Australia's research capacity in the fields of organelle genomics and evolutionary biology. Second, it will yield highly skilled young researchers: a postdoctoral fellow (Shao), a PhD student and two BSc Honours students. Third, it will generate new knowledge about genome recombination in animal mitochondria. Recombination is a fundamental, yet ....Recombination of mitochondrial genomes: what can we learn from chigger mites? This project will bring three benefits to Australia. First, it will enhance Australia's research capacity in the fields of organelle genomics and evolutionary biology. Second, it will yield highly skilled young researchers: a postdoctoral fellow (Shao), a PhD student and two BSc Honours students. Third, it will generate new knowledge about genome recombination in animal mitochondria. Recombination is a fundamental, yet poorly understood issue in mitochondrial genomics and evolutionary biology. Knowledge from this project will also improve our understanding of other important issues that are associated with animal mitochondria; like the mechanisms of mitochondrial disease and ageing, and the evolution of modern humans and other animals.Read moreRead less
Dynamic DNA structure states and memory formation. Activity-induced gene expression is central to neural plasticity, learning, and memory; however, the underlying mechanisms of these processes in the brain have yet to be fully resolved. The aim of this proposal is to obtain a deeper understanding of the functional relationship between genes and brain function. By elucidating the full repertoire of epigenetic mechanisms in the brain during learning and the formation of memory, it is hoped that t .... Dynamic DNA structure states and memory formation. Activity-induced gene expression is central to neural plasticity, learning, and memory; however, the underlying mechanisms of these processes in the brain have yet to be fully resolved. The aim of this proposal is to obtain a deeper understanding of the functional relationship between genes and brain function. By elucidating the full repertoire of epigenetic mechanisms in the brain during learning and the formation of memory, it is hoped that the true nature of brain adaptation across the lifespan will be revealed. Findings which may then provide new opportunities to strengthen, maintain and optimise cognitive function.Read moreRead less
A multi-model approach to characterise conserved regulators of lymphatic vascular development. Lymphatic vessels are important in a number of diseases affecting Australia. There is a significant gap in our basic knowledge of how lymphatic vessels form. This study will characterise key genes that control lymphatic development, providing a base of knowledge contributing to the promotion and maintenance of good health in Australia.
Cell-type specific profiling of nascent RNA in the brain during learning. This project aims to understand cell-type specific, fast-acting, and dynamic patterns of RNA expression that arise during learning and contribute to the formation of memory. Activity-induced gene expression is central to neural plasticity, learning and memory. The project will apply a new approach, which tags RNA inside living cells. The findings will be broadly applicable and create new opportunities for understanding the ....Cell-type specific profiling of nascent RNA in the brain during learning. This project aims to understand cell-type specific, fast-acting, and dynamic patterns of RNA expression that arise during learning and contribute to the formation of memory. Activity-induced gene expression is central to neural plasticity, learning and memory. The project will apply a new approach, which tags RNA inside living cells. The findings will be broadly applicable and create new opportunities for understanding the true nature of brain adaptation.Read moreRead less
Defining novel neuroepigenetic pathways that influence learning and memory. This project aims to better understand the functional relationship between epigenetic mechanisms and regulatory RNAs in the brain and how they influence learning and the formation of memory. Activity-induced gene expression is central to neural plasticity, learning, and memory. However, efforts to elucidate the underlying mechanisms in the brain have not been fully resolved. By elucidating the full repertoire of epigenet ....Defining novel neuroepigenetic pathways that influence learning and memory. This project aims to better understand the functional relationship between epigenetic mechanisms and regulatory RNAs in the brain and how they influence learning and the formation of memory. Activity-induced gene expression is central to neural plasticity, learning, and memory. However, efforts to elucidate the underlying mechanisms in the brain have not been fully resolved. By elucidating the full repertoire of epigenetic mechanisms in the brain during learning and memory formation, the findings of the project will be broadly applicable and create new opportunities for understanding the true nature of brain adaptation.Read moreRead less
Organisation, expression and diversity of the sub-telomeric regions of the ancient eukaryote, Giardia duodenalis. We propose to extend our findings on the extreme plasticity of the structure and organisation of the sub-telomeric region of the complete genome of Giardia by more extensive chromosome walking, and comparison of different isolates. These regions are subject to gene conversion, transcriptional silencing, gene mobility, recombination, variable surface protein expression, subtelomeric i ....Organisation, expression and diversity of the sub-telomeric regions of the ancient eukaryote, Giardia duodenalis. We propose to extend our findings on the extreme plasticity of the structure and organisation of the sub-telomeric region of the complete genome of Giardia by more extensive chromosome walking, and comparison of different isolates. These regions are subject to gene conversion, transcriptional silencing, gene mobility, recombination, variable surface protein expression, subtelomeric instability and the insertion of transposable elements, a dynamic balance between structural conservation and rapid evolution. This is a rare opportunity to understand the forces at work in moulding eukaryotic sub-telomeric sequences because Giardia is not constrained by sexual homogenisation and the dynamic variability is retained.Read moreRead less
Statistical methods for detection of non-coding RNAs in eukaryote genomes. Understanding how eukaryotic cells work is a major goal of 21st century biology. A crucial step will be to catalogue the functional components of eukaryotic genomes. Australian researchers must be involved in this process at an early stage, in order to maximise commercial opportunities, attract quality researchers and position ourselves for further advances. This project will make major contributions to international effo ....Statistical methods for detection of non-coding RNAs in eukaryote genomes. Understanding how eukaryotic cells work is a major goal of 21st century biology. A crucial step will be to catalogue the functional components of eukaryotic genomes. Australian researchers must be involved in this process at an early stage, in order to maximise commercial opportunities, attract quality researchers and position ourselves for further advances. This project will make major contributions to international efforts in this area, via the development of statistical methods for segmenting genomes, classification of those segments, and study of the resulting classes. In the long term, enhanced understanding of eukaryotic cells will lead to breakthroughs in biology, and to medical, pharmaceutical, agricultural and scientific advances.Read moreRead less
Co-evolution of the host pathogen interaction between Leptosphaeria maculans and Brassica species. Brassica canola is Australia's third largest export crop, producing 13% of the world's canola oil. However, blackleg disease, caused by the fungus Leptospheria maculans leads to annual yield losses of 15%, with 100% loss associated with breakdown of resistance. International investment has provided novel genome resources for Brassica and L. maculans. Applying these resources to understand the co-ev ....Co-evolution of the host pathogen interaction between Leptosphaeria maculans and Brassica species. Brassica canola is Australia's third largest export crop, producing 13% of the world's canola oil. However, blackleg disease, caused by the fungus Leptospheria maculans leads to annual yield losses of 15%, with 100% loss associated with breakdown of resistance. International investment has provided novel genome resources for Brassica and L. maculans. Applying these resources to understand the co-evolution of this plant-fungal interaction could prevent the current boom-bust cycle of canola production in Australia. This study will also provide a model and knowledge base for applications in other species, leading to enhanced crops with increased plant protection and robust, reliable productivity.Read moreRead less