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
Mobile DNA activity in the mammalian primordial germline. Early in pregnancy, a handful of cells in the embryo become primordial germ cells (PGCs). These PGCs will eventually give rise to sperm or egg cells, representing a critical inter-generational genetic link. Mobile DNA sequences target PGCs to create new heritable genetic changes. This proposal aims to analyse the activity, regulation, and consequences of mobile DNA activity in PGCs. This project expects to generate significant knowledge a ....Mobile DNA activity in the mammalian primordial germline. Early in pregnancy, a handful of cells in the embryo become primordial germ cells (PGCs). These PGCs will eventually give rise to sperm or egg cells, representing a critical inter-generational genetic link. Mobile DNA sequences target PGCs to create new heritable genetic changes. This proposal aims to analyse the activity, regulation, and consequences of mobile DNA activity in PGCs. This project expects to generate significant knowledge about the origins of mammalian genetic diversity. Expected outcomes include enhanced national and international collaborations across disciplines and new experimental systems. The expected benefit is an enhanced understanding of the mutational processes underlying genetic diversity and disease in mammals.Read moreRead less
Foundations of a good egg: correctly transitioning from mitosis to meiosis. Production of viable offspring is essential to the survival of any species. In all sexually reproducing species, this requires a unique cell type, the germ cell. Germ cells undergo a special type of cell division, called meiosis, so that they can eventually produce gametes (sperm in males and eggs in females). This project aims to discover how germ cells halt the standard form of cell division, called mitosis, and initia ....Foundations of a good egg: correctly transitioning from mitosis to meiosis. Production of viable offspring is essential to the survival of any species. In all sexually reproducing species, this requires a unique cell type, the germ cell. Germ cells undergo a special type of cell division, called meiosis, so that they can eventually produce gametes (sperm in males and eggs in females). This project aims to discover how germ cells halt the standard form of cell division, called mitosis, and initiate meiotic division instead. It is important to understand all the fundamental processes that occur during normal germ cell development so that, in the future, we can use this knowledge to support agricultural advances, rescue endangered species and solve human problems such as infertility and genetic disease.Read moreRead less
Mechanisms that control the inheritance of mitochondrial DNA mutations. How do humans and other organisms prevent the accumulation of dangerous mitochondrial genome (mtDNA) mutations across generations? This Project aims to uncover the cellular and molecular pathways that help prevent the inheritance of mtDNA mutations to offspring by employing cutting-edge genetic technologies that the laboratory has recently developed in the germline of an animal model system. This Project will generate new kn ....Mechanisms that control the inheritance of mitochondrial DNA mutations. How do humans and other organisms prevent the accumulation of dangerous mitochondrial genome (mtDNA) mutations across generations? This Project aims to uncover the cellular and molecular pathways that help prevent the inheritance of mtDNA mutations to offspring by employing cutting-edge genetic technologies that the laboratory has recently developed in the germline of an animal model system. This Project will generate new knowledge in the area of mitochondrial genetics and evolution. Expected outcomes include the development of new theories for mtDNA inheritance, which should provide significant benefits for agricultural breeding programs and the interpretation of mtDNA inheritance patterns in the human population.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
Morphological development of the kidney – a paradigm for organogenesis. This project aims to shed new light on how the kidney develops, how normal adult function is established and how congenital kidney malformations occur. It aims to investigate a mathematical pattern that has been discovered in the program of branching morphogenesis which dictates kidney development. By combining cutting-edge genetic approaches, morphological analysis and mathematical modelling, this project plans to explore h ....Morphological development of the kidney – a paradigm for organogenesis. This project aims to shed new light on how the kidney develops, how normal adult function is established and how congenital kidney malformations occur. It aims to investigate a mathematical pattern that has been discovered in the program of branching morphogenesis which dictates kidney development. By combining cutting-edge genetic approaches, morphological analysis and mathematical modelling, this project plans to explore how this pattern is established, how it dictates kidney development and whether it constitutes an ancient mechanism central to organ formation. Project outcomes may improve understanding of fundamental developmental processes and developmental disease and variation. Project findings may also be important for understanding the development of other organ systems.Read moreRead less
How do mammalian germ cells transition from mitosis to meiosis? This project aims to determine how germ cells are regulated in the mammalian embryo. Germ cells go on to form the sperm and eggs and are, therefore, critical for reproduction. In particular, this project expects to generate new knowledge about the process of meiosis, a cellular process that is specific to the germ cells. Expected outcomes will inform efforts to control fertility and infertility in livestock, humans and other mammali ....How do mammalian germ cells transition from mitosis to meiosis? This project aims to determine how germ cells are regulated in the mammalian embryo. Germ cells go on to form the sperm and eggs and are, therefore, critical for reproduction. In particular, this project expects to generate new knowledge about the process of meiosis, a cellular process that is specific to the germ cells. Expected outcomes will inform efforts to control fertility and infertility in livestock, humans and other mammalian animals (e.g. pets and endangered species). They are also likely to inform the discipline of stem cell biology in general.Read moreRead less
The Epigenetics of Sex in the Dragon. Genetic codes do not directly translate to phenotypes -- environment acts through epigenetics to modify development. We use advanced molecular techniques to examine how epigenetics responds to temperature to reverse sex in our novel animal model, the dragon lizard. How does the cell sense temperature? Once the extrinsic signal is captured, how does it influence chromatin modification to release or suppress key genes in the sex differentiation pathway? Which ....The Epigenetics of Sex in the Dragon. Genetic codes do not directly translate to phenotypes -- environment acts through epigenetics to modify development. We use advanced molecular techniques to examine how epigenetics responds to temperature to reverse sex in our novel animal model, the dragon lizard. How does the cell sense temperature? Once the extrinsic signal is captured, how does it influence chromatin modification to release or suppress key genes in the sex differentiation pathway? Which sex genes are targets? Epigenetic enzymes are astonishingly conserved, providing exciting opportunities to draw from human systems to unravel novel signatures of temperature-induced sex switching in reptiles. This project will advance knowledge of developmental programming generally.Read moreRead less