Modern reptiles with ancient toxins: the molecular origin and evolution of novel bioactive proteins from squamate dental glands. Animal venoms provide a rich source of novel bioactive proteins, some of which have demonstrated therapeutically useful activities. Through this researcher's unique approach of investigating previously unmapped squamate venom systems, there is potential for the identification of divergent, bioactive proteins. Those already identified by the applicant in the dental gl ....Modern reptiles with ancient toxins: the molecular origin and evolution of novel bioactive proteins from squamate dental glands. Animal venoms provide a rich source of novel bioactive proteins, some of which have demonstrated therapeutically useful activities. Through this researcher's unique approach of investigating previously unmapped squamate venom systems, there is potential for the identification of divergent, bioactive proteins. Those already identified by the applicant in the dental glands of Australian monitor lizard species represent a tremendous opportunity for biodiscovery. Further knowledge in this area will increase medical understandings of bites and aid conservation measures informed by the natural history of these animals.Read moreRead less
Characterisation of heavy metal transport genes in the plant Arabidopsis: potential roles in metal detoxification and accumulation. Plants have considerable potential for the bioremediation ("phytoremediation") of contaminated soils, including soils polluted with heavy metals. Progress has been made in understanding the physiological and biochemical mechanisms by which plants accumulate and detoxify heavy metals. One important aspect of metal detoxification is the transport of metals across cell ....Characterisation of heavy metal transport genes in the plant Arabidopsis: potential roles in metal detoxification and accumulation. Plants have considerable potential for the bioremediation ("phytoremediation") of contaminated soils, including soils polluted with heavy metals. Progress has been made in understanding the physiological and biochemical mechanisms by which plants accumulate and detoxify heavy metals. One important aspect of metal detoxification is the transport of metals across cell membranes. The recently completed genome project for the model plant Arabidopsis has identified a family of genes encoding heavy metal transport proteins. This project aims to investigate the roles of these genes in metal detoxification. In the longer term this knowledge can be applied to the improvement of phytoremediation processes.Read moreRead less
Mechanisms of zinc transport and homeostasis in the plant, Arabidopsis. Zinc-deficiency is one of the most widespread factors limiting crop production and affects many soils of south-east and south-west Australia. Certain zinc-efficient (ZE) crop cultivars are able to grow well under zinc deficient conditions but the genetic basis for ZE is not well understood. Using a model organism such as Arabidopsis to identify genes in plants that are important in zinc transport and homeostasis will ultimat ....Mechanisms of zinc transport and homeostasis in the plant, Arabidopsis. Zinc-deficiency is one of the most widespread factors limiting crop production and affects many soils of south-east and south-west Australia. Certain zinc-efficient (ZE) crop cultivars are able to grow well under zinc deficient conditions but the genetic basis for ZE is not well understood. Using a model organism such as Arabidopsis to identify genes in plants that are important in zinc transport and homeostasis will ultimately allow us to assess whether the homologous genes in crop species are responsible for ZE. This may contribute to more rapid and directed strategies in breeding ZE crop cultivars.Read moreRead less
Regulation of mammalian differentiation by methylation of histones and transcription factors. The objective of this proposal is to examine the functional role of arginine and lysine methylation during skeletal muscle differentiation. Differentiation, i.e the acquisition of a specific phenotype, is the biological end point of the ?Genome-Phenome? transition. Specifically, the proposal will seek to understand the role of protein methylation in the control of tissue specific gene expression and ce ....Regulation of mammalian differentiation by methylation of histones and transcription factors. The objective of this proposal is to examine the functional role of arginine and lysine methylation during skeletal muscle differentiation. Differentiation, i.e the acquisition of a specific phenotype, is the biological end point of the ?Genome-Phenome? transition. Specifically, the proposal will seek to understand the role of protein methylation in the control of tissue specific gene expression and cell signaling during differentiation. Key areas of study in the ARC priority area of Genome-Phenome research. We will test the hypothesis that the activity/function of the hierarchical myogenic transcription factors and cofactors that control skeletal myogenesis is influenced by protein methylation.Read moreRead less
The role of the neuronal Hu proteins in the regulation of the BMP signalling pathway. We aim to understand the critical decision of a neural progenitor to commit to becoming a neuron. The BMP signalling pathway is central in this decision. Neural progenitors appear to become insensitive to BMP signals, and this lack of signalling leads to neuronal differentiation. We hypothesise that neuronal identity is regulated by an unusual genetic switch- the translational regulation by the neuronal Hu pr ....The role of the neuronal Hu proteins in the regulation of the BMP signalling pathway. We aim to understand the critical decision of a neural progenitor to commit to becoming a neuron. The BMP signalling pathway is central in this decision. Neural progenitors appear to become insensitive to BMP signals, and this lack of signalling leads to neuronal differentiation. We hypothesise that neuronal identity is regulated by an unusual genetic switch- the translational regulation by the neuronal Hu proteins of two proteins in the BMP pathway. Verification of a post-transcriptional regulatory mechanism for cell fate determination would be a major discovery, and may prompt investigation of how to harness the neuron-inducing function of the Hu proteins to address the therapeutic need for new neurons in neurologic diseases.Read moreRead less
The Cytochrome P450 Gene Super-family in Drosophila melanogaster; Gene Function and Insecticide Resistance. The cytochrome P450 (Cyp) gene super-family is represented by over 90 sequences in the genome of the vinegar fly, Drosophila melanogaster. To date, four Cyp genes are found to be involved in insecticide resistance. The function of the majority of Cyp genes is unknown. This project will investigate the function and regulation of D. melanogaster Cyp genes, linking the fly's genotype to its ....The Cytochrome P450 Gene Super-family in Drosophila melanogaster; Gene Function and Insecticide Resistance. The cytochrome P450 (Cyp) gene super-family is represented by over 90 sequences in the genome of the vinegar fly, Drosophila melanogaster. To date, four Cyp genes are found to be involved in insecticide resistance. The function of the majority of Cyp genes is unknown. This project will investigate the function and regulation of D. melanogaster Cyp genes, linking the fly's genotype to its phenotype. By studying the effects of Cyp genes on fly survival, Cyp gene expression and regulation, and expressing selected Cyp genes in a yeast expression system, we will enhance our understanding of Cyp gene function and evolution.Read moreRead less
Role of mRNA polyadenylation control in gene expression. Several benefits would come from a more complete understanding of the function of the messenger RNA poly(A) tail. It is frequently targeted by mechanisms that control cellular protein synthesis. This is most evident in developmental biology, where tail length control regulates maternal mRNA expression. Our previous work suggests that it has much wider importance for cellular function than previously thought and thus its study will produce ....Role of mRNA polyadenylation control in gene expression. Several benefits would come from a more complete understanding of the function of the messenger RNA poly(A) tail. It is frequently targeted by mechanisms that control cellular protein synthesis. This is most evident in developmental biology, where tail length control regulates maternal mRNA expression. Our previous work suggests that it has much wider importance for cellular function than previously thought and thus its study will produce knowledge of broad relevance to modern life sciences and its applications in medicine and biotechnology. Finally, a better understanding of yeast cellular biology is of benefit to the food and biotechnology sector of industry.Read moreRead less
Application of genome-wide transcriptional analysis to identifying genetic markers for industrial fermentation processes. This project aims to identify yeast genes involved in the response of commercial strains to stress, to determine their role in fermentation and the genetic pathways through which they operate. The ultimate goals are to determine the impact on fermentation activity of stress, and to develop predictive methods for assessing such conditions. This has significance since stress ....Application of genome-wide transcriptional analysis to identifying genetic markers for industrial fermentation processes. This project aims to identify yeast genes involved in the response of commercial strains to stress, to determine their role in fermentation and the genetic pathways through which they operate. The ultimate goals are to determine the impact on fermentation activity of stress, and to develop predictive methods for assessing such conditions. This has significance since stress during fermentation represents a significant commercial loss. The outcomes of this work will be a better understanding of how yeast responds to stress, and the identification of genes that can be used by the commercial partner to monitor and ensure fermentation efficiency.Read moreRead less
Determining the sequence of events during eukaryotic translation initiation. Multiple benefits will arise from a more complete understanding of translation initiation. It is a frequent target for mechanisms that control gene expression and its dys-regulation is associated with human disease. For example, this is evident in cancer biology, since altered translation is a frequent cause of tumorigenesis. Translation is of universal importance for cellular function and knowledge of how it works is c ....Determining the sequence of events during eukaryotic translation initiation. Multiple benefits will arise from a more complete understanding of translation initiation. It is a frequent target for mechanisms that control gene expression and its dys-regulation is associated with human disease. For example, this is evident in cancer biology, since altered translation is a frequent cause of tumorigenesis. Translation is of universal importance for cellular function and knowledge of how it works is central to modern life sciences and its application to medical and biotechnological problems. Finally, a better understanding of yeast cellular biology is of benefit to the food and biotechnology sector of industry.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