Investigating differences in decision-making ability in older adults. This project aims to investigate how healthy ageing impacts decision making and its associated neural circuits using computation modelling and neurogenetic methods. Decision-making is a fundamental cognitive ability, allowing us to choose the best course of action. This project will investigate the relationship between genes and decision-making performance across the adult lifespan. Expected outcomes include a deeper understan ....Investigating differences in decision-making ability in older adults. This project aims to investigate how healthy ageing impacts decision making and its associated neural circuits using computation modelling and neurogenetic methods. Decision-making is a fundamental cognitive ability, allowing us to choose the best course of action. This project will investigate the relationship between genes and decision-making performance across the adult lifespan. Expected outcomes include a deeper understanding of how decision-making evolves in healthy ageing, and a tool based on genetic scores and computational modelling to predict an individual's trajectory of cognitive function. This could help identify individuals who are at risk for cognitive decline, which could then inform better interventions.Read moreRead less
Truncating presenilin mutations and their effects on gamma-secretase activity, tau and beta-catenin - insights into Alzheimers disease and cancer. Cancer and dementia are primarily afflictions of the aged and are increasingly important in an aging Australian population. 95% of all Alzheimer's disease is spontaneous (not inherited) but we know little about the molecular mechanisms underlying it. Our discovery that truncated presenilin proteins potently inhibit normal protein function suggests tha ....Truncating presenilin mutations and their effects on gamma-secretase activity, tau and beta-catenin - insights into Alzheimers disease and cancer. Cancer and dementia are primarily afflictions of the aged and are increasingly important in an aging Australian population. 95% of all Alzheimer's disease is spontaneous (not inherited) but we know little about the molecular mechanisms underlying it. Our discovery that truncated presenilin proteins potently inhibit normal protein function suggests that changes in presenilin function in aged cells might be a common molecular link between spontaneous and inherited Alzheimer's disease and could contribute to frontotemporal dementia and cancer. Our research will show whether this phenomenon might provide a breakthrough in our understanding of these diseases and be a productive area for research into their amelioration and/or prevention.Read moreRead less
Hidden complexity in microRNA function. This project aims to determine the extent to which microRNAs function through “non-canonical” mechanisms within cell nuclei, how their roles are expanded by naturally occurring sequence variation and how their activity is controlled by little known families of genes that sequester and inhibit their availability. The knowledge generated is significant as microRNAs regulate the expression of virtually all genes and biological processes, yet these mechanisms ....Hidden complexity in microRNA function. This project aims to determine the extent to which microRNAs function through “non-canonical” mechanisms within cell nuclei, how their roles are expanded by naturally occurring sequence variation and how their activity is controlled by little known families of genes that sequester and inhibit their availability. The knowledge generated is significant as microRNAs regulate the expression of virtually all genes and biological processes, yet these mechanisms of function remain poorly characterised and seldom considered. The expected outcome of better understanding mechanisms through which microRNAs work should provide significant benefit to safe and effective development of microRNAs for future agricultural or therapeutic application.Read moreRead less
Transcriptional regulation by microRNAs. This project aims to better understand microRNAs, which are of central importance to how genes are regulated. Despite recent data indicating microRNAs may also play more extensive and diverse roles as nuclear regulators of gene transcription, research has been restricted to their well known mechanism of action in the cytoplasm where they post transcriptionally silence genes. This project will investigate the potential for microRNAs to regulate transcripti ....Transcriptional regulation by microRNAs. This project aims to better understand microRNAs, which are of central importance to how genes are regulated. Despite recent data indicating microRNAs may also play more extensive and diverse roles as nuclear regulators of gene transcription, research has been restricted to their well known mechanism of action in the cytoplasm where they post transcriptionally silence genes. This project will investigate the potential for microRNAs to regulate transcription on a genome-wide scale and will thereby reveal the full extent of mechanisms by which these important genetic switches control gene expression networks the characteristics of cells. This is of fundamental significance to our understanding of gene regulation.Read moreRead less
Non-coding RNAs in mammalian reproduction. This project aims to investigate the role of non-coding RNAs in mammalian sex chromosome biology and reproduction. Non-protein coding RNAs are a major regulatory mechanism in eukaryotic genomes; they can bind other RNAs or chromatin modifying complexes. However, the evolutionary trajectory and function of non-coding RNAs in sex chromosome biology and sexual development is largely unknown. This project will study non-coding RNAs in Australian mammals to ....Non-coding RNAs in mammalian reproduction. This project aims to investigate the role of non-coding RNAs in mammalian sex chromosome biology and reproduction. Non-protein coding RNAs are a major regulatory mechanism in eukaryotic genomes; they can bind other RNAs or chromatin modifying complexes. However, the evolutionary trajectory and function of non-coding RNAs in sex chromosome biology and sexual development is largely unknown. This project will study non-coding RNAs in Australian mammals to try to answer fundamental questions about how non-coding RNAs function in mammalian sexual development.Read moreRead less
Trafficking of DNA between chloroplast and nucleus in higher plants. Reliably high levels of diverse proteins can be produced in plant chloroplasts. Environmental risks are considered low for chloroplast genes because they are not transmitted by pollen. However, we recently discovered that DNA escapes from the tobacco chloroplast to the nucleus with unexpectedly high frequency. The associated environmental risks require immediate investigation. This project will determine the fate of chloroplast ....Trafficking of DNA between chloroplast and nucleus in higher plants. Reliably high levels of diverse proteins can be produced in plant chloroplasts. Environmental risks are considered low for chloroplast genes because they are not transmitted by pollen. However, we recently discovered that DNA escapes from the tobacco chloroplast to the nucleus with unexpectedly high frequency. The associated environmental risks require immediate investigation. This project will determine the fate of chloroplast DNA that has moved to the nuclear genome and gain insight into the evolutionary and environmental consequences of chloroplast DNA escape. The ubiquity of DNA escape also will be studied in an edible crop with a small genome, tomato.Read moreRead less
Analysis of interorganellar transposition of DNA. The movement of DNA between organelles is a major driving force in the eukaryotic evolution. In yeast about 75% of all nuclear genes may derive from protomitochondria. Though DNA transfer per se continues in all higher cells, including mammals, in most species the functional transfer of genes has stopped. It continues at a high rate in plants, giving them unique potential in evolutionary studies of the genome. We established experimentally that D ....Analysis of interorganellar transposition of DNA. The movement of DNA between organelles is a major driving force in the eukaryotic evolution. In yeast about 75% of all nuclear genes may derive from protomitochondria. Though DNA transfer per se continues in all higher cells, including mammals, in most species the functional transfer of genes has stopped. It continues at a high rate in plants, giving them unique potential in evolutionary studies of the genome. We established experimentally that DNA moves frequently from the plastid (chloroplast) to the nucleus. We now aim to measure the frequency of DNA transposition from the plastid to the mitochondrion. If transposition is sufficiently frequent, the approach can be used to transformation the mitochondrial genome.Read moreRead less
The molecular basis of endosymbiotic evolution. First: Timmis has a 20 year, pioneering reputation in this research area which has recently emerged as a major focus in evolutionary genetics, genomics and GM crop technology. Four years of recent ARC funding has enabled us to remain internationally competitive and significant papers and collaborative reviews in high-impact journals have resulted, to the benefit of Australia's reputation in biolological science. Second: our recent results have caus ....The molecular basis of endosymbiotic evolution. First: Timmis has a 20 year, pioneering reputation in this research area which has recently emerged as a major focus in evolutionary genetics, genomics and GM crop technology. Four years of recent ARC funding has enabled us to remain internationally competitive and significant papers and collaborative reviews in high-impact journals have resulted, to the benefit of Australia's reputation in biolological science. Second: our recent results have caused major debate about containment of GM crops. The knowledge gained from this research will provide essential information to ensure against environmental and human problems associated with transgene escape from GM crops into wild species.Read moreRead less
Spatio-temporal activation of genes in cells and mice. This project aims to develop novel genetic methods and instrumentation for the local, rapid and reversible activation of genes in cells and mice. This project expects to generate highly innovative light- and sound-based technologies that will permit to study living systems on the gene-level with unprecedented precision. Expected outcomes include new research and technology capacity to broadly address fundamental biological questions and to c ....Spatio-temporal activation of genes in cells and mice. This project aims to develop novel genetic methods and instrumentation for the local, rapid and reversible activation of genes in cells and mice. This project expects to generate highly innovative light- and sound-based technologies that will permit to study living systems on the gene-level with unprecedented precision. Expected outcomes include new research and technology capacity to broadly address fundamental biological questions and to create new applied processes. This project intends to provide significant benefits, such as enhanced knowledge generation, multidisciplinary training opportunities and patentable technologies.Read moreRead less
Evolution and function of sex chromosomes and genes in mammalian reproduction. This project will ensure Australian leadership in research of reproductive biology and genomics in platypus and echidna. As our most distant relatives, these iconic species provide an understanding of human genes contributing to medical conditions involved in sexual development, infertility and ovarian cancer.