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
Cystine flux and hydrogen peroxide breakdown in reuteri group lactobacilli. We have discovered, and aim to fully dissect a novel function of reuteri group lactobacilli. These microbes inhabit the surfaces of the gastrointestinal and reproductive tracts of humans and are also used as probiotics, and in the dairy industry. This function mediates the production and breakdown of large amounts of hydrogen peroxide, cystine and thiols. These are highly bioactive and affect human cells and other bacter ....Cystine flux and hydrogen peroxide breakdown in reuteri group lactobacilli. We have discovered, and aim to fully dissect a novel function of reuteri group lactobacilli. These microbes inhabit the surfaces of the gastrointestinal and reproductive tracts of humans and are also used as probiotics, and in the dairy industry. This function mediates the production and breakdown of large amounts of hydrogen peroxide, cystine and thiols. These are highly bioactive and affect human cells and other bacteria at the surfaces of the gastrointestinal and reproductive tracts, and thiols are also flavourants in dairy products. Our research will inform the rational development of probiotics, the management and treatment of unpleasant conditions such as Crohn's disease and bacterial vaginosis, and innovation in dairy fermentations.Read moreRead less
The function of truncated MEK1 protein in a G2 phase cell cycle delay and in mitosis. Understanding cell proliferation. Intracellular signaling pathways controlling cell growth are often mutated in cancers and other hyperproliferative diseases. Understanding precisely how these pathways operate and how mutations of these pathways can contribute to uncontrolled growth can readily provide new targets for preventative therapies or cures. We have identified a novel mechanism regulating one compone ....The function of truncated MEK1 protein in a G2 phase cell cycle delay and in mitosis. Understanding cell proliferation. Intracellular signaling pathways controlling cell growth are often mutated in cancers and other hyperproliferative diseases. Understanding precisely how these pathways operate and how mutations of these pathways can contribute to uncontrolled growth can readily provide new targets for preventative therapies or cures. We have identified a novel mechanism regulating one component of a well studied pathway, the MAPK pathway, and new functions for this component. The contribution of this novel component to mechanisms involved in regulating cell growth previously through to be controlled by the canonical MAPK pathway could change our understanding of the fundamental mechanisms controlling cell growth. Read moreRead less
Function of the unique mitotic form of MEK. Many of the mechanisms controlling normal cell growth and division are known, although there are an increasing number of examples of mechanism having more thn the originally defined functions. We have found that one well studied mechanism, the Ras-Raf-MEK-ERK pathway operates in a unique manner during the phase when cell division occurs, known as mitosis. Understanding this novel mechanism and identifying its function at this critical stage of cell d ....Function of the unique mitotic form of MEK. Many of the mechanisms controlling normal cell growth and division are known, although there are an increasing number of examples of mechanism having more thn the originally defined functions. We have found that one well studied mechanism, the Ras-Raf-MEK-ERK pathway operates in a unique manner during the phase when cell division occurs, known as mitosis. Understanding this novel mechanism and identifying its function at this critical stage of cell division will provide insights into how cell control the partitioning of replicated genome and produce two identical daugther cells.Read moreRead less
The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with res ....The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with respect to transcriptional elongation and long-range regulation. It will highlight a new approach to the therapeutic targeting of MYB in cancer: data generated from this research may enable us to target MYB expression in a range of cancers including breast cancer by inhibiting transcriptional elongation. And it will provide training in advanced molecular biology to postdoctoral scientists and students.Read moreRead less
Functional characterisation of CMAP, a novel centrosome- and midbody-associated protein. Cell division is a highly regulated process involving many components to produce two daughter cells which contain an equal amount of DNA. Thus incorrect localisation and modification of specific proteins that regulate this process cause cell division errors resulting in genomic instability. We have recently identified a novel protein called CMAP that is involved in the final stages of cell division, which in ....Functional characterisation of CMAP, a novel centrosome- and midbody-associated protein. Cell division is a highly regulated process involving many components to produce two daughter cells which contain an equal amount of DNA. Thus incorrect localisation and modification of specific proteins that regulate this process cause cell division errors resulting in genomic instability. We have recently identified a novel protein called CMAP that is involved in the final stages of cell division, which involves the cleavage of the cell membrane to produce two daughter cells. Here, we aim to characterise the mechanism(s) of CMAP function and to identify and characterise CMAP binding proteins to further understand the mechanisms involved in the final stages of cell division to maintain genomic stability.Read moreRead less
A Genomic Dissection of Natural Adaptation in Mate Recognition. Adaptation is a fundamental area of evolutionary biology but we know surprisingly little about its underlying genetic basis. As a process, adaptation poses several challenges for Australian society including bacterial evolution of resistance to antibiotics, HIV resistance to antiviral medications and the evolution of pesticide resistance in agricultural pests. This study will use a model system and genomic tools to test theoretical ....A Genomic Dissection of Natural Adaptation in Mate Recognition. Adaptation is a fundamental area of evolutionary biology but we know surprisingly little about its underlying genetic basis. As a process, adaptation poses several challenges for Australian society including bacterial evolution of resistance to antibiotics, HIV resistance to antiviral medications and the evolution of pesticide resistance in agricultural pests. This study will use a model system and genomic tools to test theoretical models of the genetic basis of adaptation. This integrative approach will enhance Australia's research profile in genomics and evolutionary biology. The project will provide emerging scientists with skills in areas including genomics, molecular biology, evolutionary biology and agricultural genetics.Read moreRead less
Maximising knowledge from dense SNP (single nucleotide polymorphisms) data using multi-locus analysis. The genomics revolution has made it possible to measure thousands of DNA variants in individuals. This information can be used in many ways, including to find genes that cause variation between individuals in a population and to estimate the size of the population in the past. Our study will lead an analysis method that will extract more information out of such data. This will improve the effi ....Maximising knowledge from dense SNP (single nucleotide polymorphisms) data using multi-locus analysis. The genomics revolution has made it possible to measure thousands of DNA variants in individuals. This information can be used in many ways, including to find genes that cause variation between individuals in a population and to estimate the size of the population in the past. Our study will lead an analysis method that will extract more information out of such data. This will improve the efficiency of gene mapping methods, including applications in humans for traits related to productive ageing and a healthy start to life, will allow the estimation of genetic relatedness and genetic variation in natural populations, and will lead to more efficient selection programs in agricultural populations.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
Origin of multicellularity in animals: identification and analysis of intercellular signalling pathways in a basal metazoan, the demosponge Reniera. The Reniera genome project is a multi-million dollar collaboration between JGI (US-DOE) and Australian scientists that will see the sequencing of the first Australian marine animal by 2006. This project will significantly advance our understanding of the origins of animals and contribute to the reconstruction of creatures that lived over 600 million ....Origin of multicellularity in animals: identification and analysis of intercellular signalling pathways in a basal metazoan, the demosponge Reniera. The Reniera genome project is a multi-million dollar collaboration between JGI (US-DOE) and Australian scientists that will see the sequencing of the first Australian marine animal by 2006. This project will significantly advance our understanding of the origins of animals and contribute to the reconstruction of creatures that lived over 600 million years ago. A major outcome of this reconstruction will be a fundamental understanding of how cells communicate with each other during the process of development to give rise to the diversity of cell types within multicellular animals. This study will also shed light on what happens when cell communication goes astray, as observed in a range of human malignancies, including cancer. Read moreRead less