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
The molecular basis of cold adaptation: an integrated genomic and proteomic study of Antarctic archaea. The project enables Australia to remain a world leader in extremophiles, cold adaptation and Antarctic biology, strengthening the reputation Australian scientists have in scientific programs of global significance and fostering the interests of the international community in sciences ranging from bioprospecting to the search for extraterrestrial life. National benefit is directly derived from ....The molecular basis of cold adaptation: an integrated genomic and proteomic study of Antarctic archaea. The project enables Australia to remain a world leader in extremophiles, cold adaptation and Antarctic biology, strengthening the reputation Australian scientists have in scientific programs of global significance and fostering the interests of the international community in sciences ranging from bioprospecting to the search for extraterrestrial life. National benefit is directly derived from technological innovation and training local scientists in modern biology of environmental microorganisms. The Antarctic microorganisms provide unique compounds, enzymes and molecules for biotechnology and industry. Insight will be gained into the critical role that methanogens play in the global carbon cycle and global warming.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
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
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
Genetic variation of single cell transcriptional heterogeneity in HiPSCs. This project aims to investigate whether induced pluripotent stem cells (iPSC) can be used to study the functions of genetic variants associated with human phenotypes and cell fate decisions. The project will utilise technology to produce single cell RNA sequence data for 100,000s of cells. By sequencing individual cells, the genetic control of cellular heterogeneity both within and between cells can be identified, and in ....Genetic variation of single cell transcriptional heterogeneity in HiPSCs. This project aims to investigate whether induced pluripotent stem cells (iPSC) can be used to study the functions of genetic variants associated with human phenotypes and cell fate decisions. The project will utilise technology to produce single cell RNA sequence data for 100,000s of cells. By sequencing individual cells, the genetic control of cellular heterogeneity both within and between cells can be identified, and in doing so, will provide significant benefit by revealing the potential for iPSC to be used for functional translation of human genomics.Read moreRead less
Photosynthetic traits as “key performance indicators” of coral health. The objective of this project is to advance knowledge on the healthy functioning of the coral–algal symbiosis, which defines the response of coral reef ecosystems to worldwide environmental change. Current approaches to address this problem have linked coral health to algal symbiont diversity but have been unable to resolve the fundamental symbiont functional traits that govern this link – the “key performance indicators (KPI ....Photosynthetic traits as “key performance indicators” of coral health. The objective of this project is to advance knowledge on the healthy functioning of the coral–algal symbiosis, which defines the response of coral reef ecosystems to worldwide environmental change. Current approaches to address this problem have linked coral health to algal symbiont diversity but have been unable to resolve the fundamental symbiont functional traits that govern this link – the “key performance indicators (KPIs)”. This project plans to couple advanced physiological and functional genomics techniques to transform our understanding of how algal symbiont metabolic KPIs regulate coral growth and stress susceptibility. This may provide new diagnostic capability for the assessment of coral health and may enable us to improve coral reef ecosystem management.Read moreRead less
Does developmental noise have an epigenetic basis? One's ultimate phenotype is the result of a combination of genotype and environment, and includes a poorly understood component termed ?developmental noise?. The molecular basis of developmental noise remains unknown, but it appears to be established in early development and to be retained for the life of the organism. We propose that the molecular basis of developmental noise is the epigenetic state of the genome. The stochastic nature of th ....Does developmental noise have an epigenetic basis? One's ultimate phenotype is the result of a combination of genotype and environment, and includes a poorly understood component termed ?developmental noise?. The molecular basis of developmental noise remains unknown, but it appears to be established in early development and to be retained for the life of the organism. We propose that the molecular basis of developmental noise is the epigenetic state of the genome. The stochastic nature of the establishment of epigenetic state, combined with its heritability during mitosis, provides all the essential components for developmental noise. If our hypothesis proves correct, our work will have a major impact on the understanding of one of the most basic concepts in genetics.Read moreRead less
Identification of causal variants for complex traits. The aim of this project is to identify causal variants for complex traits in cattle and humans. Although most important traits in agriculture, medicine and evolution are complex traits, very few of the genetic variants affecting these traits are known and this undermines our understanding of how genetic variants affect a trait and practical uses of this knowledge. Huge datasets of individuals with genome sequence and phenotypes and new statis ....Identification of causal variants for complex traits. The aim of this project is to identify causal variants for complex traits in cattle and humans. Although most important traits in agriculture, medicine and evolution are complex traits, very few of the genetic variants affecting these traits are known and this undermines our understanding of how genetic variants affect a trait and practical uses of this knowledge. Huge datasets of individuals with genome sequence and phenotypes and new statistical methods provide the opportunity to close this gap. The outcome will be identification of many genomic variants causing variation in complex traits. This will benefit scientific understanding of complex traits and the ability to predict traits for individuals from their genome sequence.Read moreRead less
The role of RNA editing by the brain-specific enzym ADAR3 in learning and memory. Higher-order cognition sets us apart from other species but how this is achieved is still under debate. The project will test the idea, strongly supported by recent genomic analyses, that subtle changes in the sequences of RNA in response to environmental stimuli underpin this extraordinary ability.