Cellular genomic approach to the pathogenesis of multiple sclerosis. This project compares the levels of gene usage in two important immune cell types between patients with multiple sclerosis and people who do not have the disease. It aims to identify the molecular basis for the disease, in order to identify new diagnostic, preventative and treatment options.
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
Discovery and characterization of new classes of small regulatory RNAs in mammals. The project will reaffirm and enhance Australian leadership in the most rapidly developing area of molecular biological and genetic research, by the application of ultra high-throughput sequencing technologies to discovery of regulatory RNAs, thereby to identify the characteristics of important regulatory pathways that underpin mammalian development, brain function and species diversity. The results of this resear ....Discovery and characterization of new classes of small regulatory RNAs in mammals. The project will reaffirm and enhance Australian leadership in the most rapidly developing area of molecular biological and genetic research, by the application of ultra high-throughput sequencing technologies to discovery of regulatory RNAs, thereby to identify the characteristics of important regulatory pathways that underpin mammalian development, brain function and species diversity. The results of this research will have wide implications and applications in biotechnology, genetic engineering, animal breeding, medical science and advanced informatics.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
The Genetic Basis of Differences Between the Sexes. Improved medical interventions against genetic disorders like cancer are made possible by advances in fundamental understanding of gene function and, especially, genetic mechanisms (like genomic imprinting) that are directly implicated in these disorders. Furthermore, an understanding of environmental effects within and across generations is vital in an age of global climate change. Recent theory and evidence suggest that research on sexually d ....The Genetic Basis of Differences Between the Sexes. Improved medical interventions against genetic disorders like cancer are made possible by advances in fundamental understanding of gene function and, especially, genetic mechanisms (like genomic imprinting) that are directly implicated in these disorders. Furthermore, an understanding of environmental effects within and across generations is vital in an age of global climate change. Recent theory and evidence suggest that research on sexually dimorphic traits may hold a key to a better understanding of these phenomena. The proposed research will strengthen Australia's position as leader in evolutionary genetics, enhance knowledge of native fauna, and improve our understanding of biological phenomena that affect human health. Read moreRead less
Searching for genes influencing reading ability using multivariate genomic linkage analysis and allelic association analysis. Following from the replicated linkages of reading disability to loci on chromosomes 6 & 18, this study examines linkage of these same regions to a range of reading measures in an unselected sample of twins and siblings. Preliminary univariate linkage scans of two neuropsychological reading indices suggest linkage to loci on two chromosomes. Our next step is to include rea ....Searching for genes influencing reading ability using multivariate genomic linkage analysis and allelic association analysis. Following from the replicated linkages of reading disability to loci on chromosomes 6 & 18, this study examines linkage of these same regions to a range of reading measures in an unselected sample of twins and siblings. Preliminary univariate linkage scans of two neuropsychological reading indices suggest linkage to loci on two chromosomes. Our next step is to include reading measures of orthographic skill and phonological decoding in a multivariate linkage analysis with the other reading indices and with measures of IQ and academic achievement. Multivariate linkage increases the power of detecting quantitative traits and assists in defining the phenotype related to the locus. We then aim to identify the functional gene through allelic association analysis. Identification of QTLs for reading ability may lead to practical outcomes such as the behavioural and biomedical management of reading deficits, which may then benefit areas such as scholastic achievement.Read moreRead less
Locating genes for elementary and complex cognitive abilities using genetic linkage and association analysis. This study aims to identify genes influencing cognitive ability by using multiple measures of cognition in combination with genetic linkage and association analyses. Multiple measures can increase the statistical power of finding a gene and provide a more comprehensive framework for charting the functional role of genes. The outcome of locating genes for cognition will provide insight i ....Locating genes for elementary and complex cognitive abilities using genetic linkage and association analysis. This study aims to identify genes influencing cognitive ability by using multiple measures of cognition in combination with genetic linkage and association analyses. Multiple measures can increase the statistical power of finding a gene and provide a more comprehensive framework for charting the functional role of genes. The outcome of locating genes for cognition will provide insight into biological functions of the brain which affect human intellect, and will have downstream practical applications which could include better educational, behavioural and biomedical management of learning and memory disorders, and of other intellectual disabilities.Read moreRead less
Quantitative and Molecular Genetic Analysis of Cognition. This study attempts to unravel the pathways through which genes may exert their influence on cognitive processes by identifying some of the genes associated with normal variation in cognitive ability. Using the cognitive phenotypes we have collected, both linkage and association analysis will be used to find QTLs (locations on the chromosomes at which specific genes contribute to a quantitative trait) associated with processing speed and ....Quantitative and Molecular Genetic Analysis of Cognition. This study attempts to unravel the pathways through which genes may exert their influence on cognitive processes by identifying some of the genes associated with normal variation in cognitive ability. Using the cognitive phenotypes we have collected, both linkage and association analysis will be used to find QTLs (locations on the chromosomes at which specific genes contribute to a quantitative trait) associated with processing speed and other specific abilities. The research will enhance our understanding of the biological mechanisms influencing brain function and paves the way for the genetic dissection of the brain.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
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