Evolution and function of mammalian sex chromosomes. Research on iconic Australian mammals has profoundly reshaped our understanding of reproductive biology and sex chromosome evolution. In this project we combine unique expertise, international collaboration and novel genetic information about Australia's unique egg-laying mammals (echidna and platypus) to investigate major aspects of reproduction. This work will address fundamental aspects of sex chromosome biology and advance our understandin ....Evolution and function of mammalian sex chromosomes. Research on iconic Australian mammals has profoundly reshaped our understanding of reproductive biology and sex chromosome evolution. In this project we combine unique expertise, international collaboration and novel genetic information about Australia's unique egg-laying mammals (echidna and platypus) to investigate major aspects of reproduction. This work will address fundamental aspects of sex chromosome biology and advance our understanding of mammalian reproduction. The knowledge gained will have application in captive breeding and conservation of these extraordinary Australian mammals. The project also provides opportunity to train research students in cutting edge molecular biology and informatics.Read moreRead less
Targeting the genome and epigenome of the exercising skeletal muscle. This project aims is to discover epigenetic and genetic biomarkers that predict fitness changes, following exercise intervention. Individuals are remarkably variable in their responses to exercise interventions, and a large portion of these responses is attributed to genetics, and epigenetics (the effect of the environment on the expression of genes). Using controlled exercise training as a model, this project expects to disco ....Targeting the genome and epigenome of the exercising skeletal muscle. This project aims is to discover epigenetic and genetic biomarkers that predict fitness changes, following exercise intervention. Individuals are remarkably variable in their responses to exercise interventions, and a large portion of these responses is attributed to genetics, and epigenetics (the effect of the environment on the expression of genes). Using controlled exercise training as a model, this project expects to discover epigenetic and genomic markers in skeletal muscle predictive of exercise adaptations. This will contribute to the development and future delivery of targeted and personalised exercise programs for the general population. This has important implications for improving health in the Australian population.Read moreRead less
Can exercise slow down the epigenetic ageing clock? The aged population accounts for a significant amount of Australia’s health budget. This project aims to uncover novel molecular biomarkers that slow the ageing process and maintain good health for longer. This project aims to use innovative epigenetic analysis to study the molecular ‘clocks’ of young and old populations and to test whether exercise can slow the ageing process. This is expected to lead to a better understanding of how humans re ....Can exercise slow down the epigenetic ageing clock? The aged population accounts for a significant amount of Australia’s health budget. This project aims to uncover novel molecular biomarkers that slow the ageing process and maintain good health for longer. This project aims to use innovative epigenetic analysis to study the molecular ‘clocks’ of young and old populations and to test whether exercise can slow the ageing process. This is expected to lead to a better understanding of how humans respond to changing environments during their lifetime, and will underpin the development of evidence-based personalised health interventions to keep Australians healthier for longer.
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Control of vascular form and fate by a novel pre-mRNA splicing mechanism . Vertebrate vasculature forms elaborate, branched networks essential for life. As developing vessels permeate tissues and organs, dynamic and spatiotemporally regulated cellular signalling determines the fate, patterning and distribution of new vascular networks. This project follows the recent discovery of a mechanism whereby RNA diversification through alternative splicing controls complex signalling patterns in forming ....Control of vascular form and fate by a novel pre-mRNA splicing mechanism . Vertebrate vasculature forms elaborate, branched networks essential for life. As developing vessels permeate tissues and organs, dynamic and spatiotemporally regulated cellular signalling determines the fate, patterning and distribution of new vascular networks. This project follows the recent discovery of a mechanism whereby RNA diversification through alternative splicing controls complex signalling patterns in forming vessels. This project investigates this molecular mechanism in embryo and tissue development. The project will produce fundamental knowledge in RNA diversification, vascular fate, growth and cell signalling. New knowledge generated may lead to new approaches in stem cell biology, tissue engineering and regenerative biology.Read moreRead less
Hippo signalling control of transcription in lymphatic vascular development. Lymphatic vasculature forms complex, branched networks present in almost all vertebrate tissues and organs. Signalling in lymphatic endothelial cells determines the fate, structure and function of these complex and essential networks. This project follows our recent discovery of a major role for the Hippo signalling pathway in lymphatic vascular development. It aims to investigate how Hippo signalling regulates essenti ....Hippo signalling control of transcription in lymphatic vascular development. Lymphatic vasculature forms complex, branched networks present in almost all vertebrate tissues and organs. Signalling in lymphatic endothelial cells determines the fate, structure and function of these complex and essential networks. This project follows our recent discovery of a major role for the Hippo signalling pathway in lymphatic vascular development. It aims to investigate how Hippo signalling regulates essential target genes that drive lymphatic development. The project expects to generate fundamental knowledge in vascular signalling, transcription and the control of vascular network growth and expansion. Outcomes may provide significant benefits in new approaches in stem cell biology, tissue engineering and regenerative biology. Read moreRead less
Unlocking the secrets of metabolic variation in a highly diverse bacterium. This project aims to explore metabolic diversity of Klebsiella pneumoniae, a bacterium relevant to the agricultural, veterinary, medical and biotechnology industries. It is expected to reveal significant insights into the biology of this diverse organism via an innovative combination of DNA sequence analyses and metabolic modelling. Expected outcomes include 4500 novel metabolic models and a novel population metabolic fr ....Unlocking the secrets of metabolic variation in a highly diverse bacterium. This project aims to explore metabolic diversity of Klebsiella pneumoniae, a bacterium relevant to the agricultural, veterinary, medical and biotechnology industries. It is expected to reveal significant insights into the biology of this diverse organism via an innovative combination of DNA sequence analyses and metabolic modelling. Expected outcomes include 4500 novel metabolic models and a novel population metabolic framework. This should provide major benefits for understanding bacterial ecology and evolution, and for future studies seeking to optimise industrial processes or prevent disease. It will also directly contribute to building Australia’s capacity in computational biology- a key driver of biotechnology innovation.Read moreRead less
Imaging mammalian organogenesis with adaptive optics. Optical and computational barriers to analysing cell movement have limited our understanding of mammalian organogenesis. We have built a super-resolution spinning disk confocal microscope with adaptive optics and developed machine learning-based image processing and cell segmentation workflows to overcome these long-standing barriers. We propose to combine these cutting-edge live imaging and analysis approaches to characterise the role of cel ....Imaging mammalian organogenesis with adaptive optics. Optical and computational barriers to analysing cell movement have limited our understanding of mammalian organogenesis. We have built a super-resolution spinning disk confocal microscope with adaptive optics and developed machine learning-based image processing and cell segmentation workflows to overcome these long-standing barriers. We propose to combine these cutting-edge live imaging and analysis approaches to characterise the role of cell movement in mammalian organ formation and develop advanced cell segmentation and tracking methods for use in the scientific community. We anticipate this project will generate fundamental insights into how cells interact to build complex organs.Read moreRead less
Ancestral, conserved and novel mechanisms in marsupial genomic imprinting. Genomic imprinting is the differential expression pattern of some genes depending on whether the gene copy came from the mother or the father. This differential expression is essential for embryonic development and errors lead to disease. To date, most of our knowledge of the control of genomic imprinting comes from the mouse, but much less is known about this process in marsupials. Our comparative approach, using marsupi ....Ancestral, conserved and novel mechanisms in marsupial genomic imprinting. Genomic imprinting is the differential expression pattern of some genes depending on whether the gene copy came from the mother or the father. This differential expression is essential for embryonic development and errors lead to disease. To date, most of our knowledge of the control of genomic imprinting comes from the mouse, but much less is known about this process in marsupials. Our comparative approach, using marsupial mammals that are distantly related to mice and humans, aims to clarify how genomic imprinting mechanisms have evolved, which patterns are conserved across mammals, and which vary. Our proposed research aims to provide new approaches and understanding of this fundamental process essential for the continuation of life.
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Prediction of phenotype for multiple traits from multi-omic data. This project aims to develop better methods for predicting traits in an individual based on their genome sequence. This method will be tested in agricultural animals and plants and in humans. The prediction formula is derived from a training dataset that has information on the traits and genome sequence of a sample of individuals. The prediction formula can then be applied to predict the trait in individuals where the trait is un ....Prediction of phenotype for multiple traits from multi-omic data. This project aims to develop better methods for predicting traits in an individual based on their genome sequence. This method will be tested in agricultural animals and plants and in humans. The prediction formula is derived from a training dataset that has information on the traits and genome sequence of a sample of individuals. The prediction formula can then be applied to predict the trait in individuals where the trait is unknown. This is useful for selecting the best parents for breeding in agriculture and for predicting the future phenotype of animals, crops and people. The proposed method uses data on very many traits to identify sequence variants that have a function and to predict the traits affected by each variant.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