Regulation of the EphA3 receptor tyrosine kinase in vertebrate development. The Eph/ephrin system has a critical role in normal embryonic development. Amongst vertebrates, the EphA3 gene is one of the most highly conserved genes in this system with critical roles in development of the visual system and in other developmental processes. Understanding how this gene is regulated will help us to understand the critical role of EphA3 in the basic biology of humans and other animals. This knowledge ma ....Regulation of the EphA3 receptor tyrosine kinase in vertebrate development. The Eph/ephrin system has a critical role in normal embryonic development. Amongst vertebrates, the EphA3 gene is one of the most highly conserved genes in this system with critical roles in development of the visual system and in other developmental processes. Understanding how this gene is regulated will help us to understand the critical role of EphA3 in the basic biology of humans and other animals. This knowledge may also shed light on the basis of congenital abnormalities and other pathological processes and possibly help us to understand how to prevent or treat these conditions.Read moreRead less
A Genomic analysis of macrophage differentiation: Epigenetic factors that determine transcriptional choices in a lineage dependant manner. Our genetic information is fundamental to who we are, how we develop, & how we age. This project will build the research capacity of Australia's genome sciences, providing an analytical framework to describe & study the many products expressed from any single gene and to assess the function of genetic variation & test genome regulatory events. An immediate ou ....A Genomic analysis of macrophage differentiation: Epigenetic factors that determine transcriptional choices in a lineage dependant manner. Our genetic information is fundamental to who we are, how we develop, & how we age. This project will build the research capacity of Australia's genome sciences, providing an analytical framework to describe & study the many products expressed from any single gene and to assess the function of genetic variation & test genome regulatory events. An immediate outcome is a better understanding of the regulation of our immune system. This approach will fuel the discovery of new signalling molecules & their effects on a population of cells, & likewise provides a novel approach to study the dysregulation of cell signalling pathways.Read moreRead less
Alternative Splicing in the Mouse Transcriptome. Although the human genome completion is cause for excitement we do not have any firm indication of precisely how many protein-coding genes exist in a mammalian genome. We have even less indication of the extent to which these genes generate alternative gene products, through a process termed alternative splicing. The detection and sequencing of these full-length alternative gene products is the focus of this application. This application details t ....Alternative Splicing in the Mouse Transcriptome. Although the human genome completion is cause for excitement we do not have any firm indication of precisely how many protein-coding genes exist in a mammalian genome. We have even less indication of the extent to which these genes generate alternative gene products, through a process termed alternative splicing. The detection and sequencing of these full-length alternative gene products is the focus of this application. This application details the opportunity to participate in the identification of the full transcriptome of the mouse and is part of a collaborative effort with The RIKEN Genome Sciences Center in Japan.Read moreRead less
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
Can muscles tune foot stiffness to enhance efficiency of human locomotion? This project aims to understand the key role that muscles might play in supporting the arch of the foot and determine if this improves the efficiency of human walking and running. The human foot is known to act like a spring to store and return energy during walking and running. The project hypothesises that this function is enhanced by muscular contributions within the foot that act to tune the stiffness of the foot and ....Can muscles tune foot stiffness to enhance efficiency of human locomotion? This project aims to understand the key role that muscles might play in supporting the arch of the foot and determine if this improves the efficiency of human walking and running. The human foot is known to act like a spring to store and return energy during walking and running. The project hypothesises that this function is enhanced by muscular contributions within the foot that act to tune the stiffness of the foot and maximise efficiency of force production. Exploration of how foot stiffness is controlled during human movement is expected to improve our understanding of the evolution of human walking and running and contribute to improving the design of modern footwear.Read moreRead less
To investigate the role of the protein kinase SMG-1 in the stress response. This project is included in the designated priority area of research Promoting and Maintaining Good Health and Ageing Well. It represents a mouse model to assist in the study of human disease. It is the first mouse model for SMG-1, a protein kinase that protects against a variety of different forms of stress. The strength of the model is that it can be combined with other mouse models to interrogate and elucidate the eve ....To investigate the role of the protein kinase SMG-1 in the stress response. This project is included in the designated priority area of research Promoting and Maintaining Good Health and Ageing Well. It represents a mouse model to assist in the study of human disease. It is the first mouse model for SMG-1, a protein kinase that protects against a variety of different forms of stress. The strength of the model is that it can be combined with other mouse models to interrogate and elucidate the events occurring in different pathways for stress. The expectation is that ground-breaking data will be generated with this model providing scientific leadership on the role of this protein. It will also assist in establishing new collaborations.Read moreRead less
Identification of functionally important autophosphorylation site(s) on ataxia telangiectasia and Rad 3 - related (ATR) protein kinase. The integrity of our genetic material must be maintained so that it can be passed on from one generation to the next and also to minimize the risk of cancer and other pathologies in an individual. There are multiple proteins involved in protecting our DNA including several enzymes that detect and signal DNA damage to a series of pathways involved in halting the ....Identification of functionally important autophosphorylation site(s) on ataxia telangiectasia and Rad 3 - related (ATR) protein kinase. The integrity of our genetic material must be maintained so that it can be passed on from one generation to the next and also to minimize the risk of cancer and other pathologies in an individual. There are multiple proteins involved in protecting our DNA including several enzymes that detect and signal DNA damage to a series of pathways involved in halting the passage of cells through the cell cycle so that repair can occur. This project studies the mechanism of action of one of these enzymes which will be of benefit in designing new compounds to fight disease. 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
Testing metabolic theories in ecology. There are striking similarities in the way plants and animals take up and use energy (metabolism), despite enormous variation in size and life-style. This project will make the first experimental comparison of the predictions of the two major theories for these broad patterns. The results will significantly progress this controversial and exciting field.
Unsaturation of vapour pressure inside leaves: fundamental, but unknown. This project aims to determine when and to what extent the air inside leaves becomes unsaturated with water vapour. All current interpretation and modelling of leaf gas exchange assumes saturation under all circumstances. Compelling evidence has been obtained that suggests this is not true under moderate air vapour pressure deficits. A novel technique will be employed to assess the water vapour concentration of the air insi ....Unsaturation of vapour pressure inside leaves: fundamental, but unknown. This project aims to determine when and to what extent the air inside leaves becomes unsaturated with water vapour. All current interpretation and modelling of leaf gas exchange assumes saturation under all circumstances. Compelling evidence has been obtained that suggests this is not true under moderate air vapour pressure deficits. A novel technique will be employed to assess the water vapour concentration of the air inside leaves based on stable isotope analysis of carbon dioxide and water vapour exchanged between leaves and air. The project is expected to provide fundamental knowledge about how stomata regulate photosynthesis and water use, with significant implications for modelling vegetation function and for improving the performance of crop plants.Read moreRead less