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
Complex trait analyses based on genome-wide approaches. This project aims to develop whole genome approaches that can improve the estimation and prediction power by using information from the dynamic genetic architecture of complex traits (i.e. the changes of genetic characteristics and effects when varying effective population size and genetic backgrounds). The project intends to deliver advanced statistical models, efficient algorithms and design by combining data from close relatives, populat ....Complex trait analyses based on genome-wide approaches. This project aims to develop whole genome approaches that can improve the estimation and prediction power by using information from the dynamic genetic architecture of complex traits (i.e. the changes of genetic characteristics and effects when varying effective population size and genetic backgrounds). The project intends to deliver advanced statistical models, efficient algorithms and design by combining data from close relatives, population samples or from different populations (e.g. multi-ethnicities or multi-breeds). The expected outcome is to better understand the dynamic architecture of complex traits and develop methods with improved power, precision and accuracy in genomic analyses.Read moreRead less
Whole-genome multivariate reaction norm model for complex traits. This project aims to develop a multivariate whole-genome genotype-covariate correlation and interaction model that can be applied to a wide range of existing genome-wide association study (GWAS) datasets. Genotype-covariate correlation and interaction (GCCI) are fundamental in biology but there is no standard approach to disentangle interaction from correlation in the whole-genome analyses. This project will address the key featur ....Whole-genome multivariate reaction norm model for complex traits. This project aims to develop a multivariate whole-genome genotype-covariate correlation and interaction model that can be applied to a wide range of existing genome-wide association study (GWAS) datasets. Genotype-covariate correlation and interaction (GCCI) are fundamental in biology but there is no standard approach to disentangle interaction from correlation in the whole-genome analyses. This project will address the key feature in biology, which relates to dissecting the complex mechanism of association and interaction. The proposed statistical model implemented in a context of a novel design based on multiple GWAS data sets is a paradigm shifting-tool with applications to multiple industries.Read moreRead less
Discovering the pathways and mechanisms underlying bio-insecticide control of the global migratory pest, diamondback moth, Plutella xylostella. Sustaining crop yield and maintaining food security is a significant worldwide concern. This project aims to strengthen insect pest control strategies and improve bio-insecticide use in agriculture through better understanding of the mode of action of Bacillus thuringiensis (Bt) insecticides. It aims to improve their efficacy and evaluate opportunities t ....Discovering the pathways and mechanisms underlying bio-insecticide control of the global migratory pest, diamondback moth, Plutella xylostella. Sustaining crop yield and maintaining food security is a significant worldwide concern. This project aims to strengthen insect pest control strategies and improve bio-insecticide use in agriculture through better understanding of the mode of action of Bacillus thuringiensis (Bt) insecticides. It aims to improve their efficacy and evaluate opportunities to develop bio-insecticides based on plant saponins. This will assist in determining the risk of insecticide resistant moths migrating to Australia, and within our borders. This project aims to provide opportunities to improve transgenic Bt-crops and Bt-sprays, provide commercial development of new bio-insecticides, and develop optimal control strategies for major Australian migratory pests.Read moreRead less
Genetic dissection of a regulatory deubiquitlyation network. The potential impact of this work is widespread, because although it is known that ubiquitlyation has regulatory consequences in multicellular eukaryotes, individual networks have not been completely described in higher eukaryotes. Knowledge gained about fundamental processes in the A. nidulans model system is directly applicable to fungi used in biotechnology in the food, beverage, enzyme and pharmaceutical production industries, and ....Genetic dissection of a regulatory deubiquitlyation network. The potential impact of this work is widespread, because although it is known that ubiquitlyation has regulatory consequences in multicellular eukaryotes, individual networks have not been completely described in higher eukaryotes. Knowledge gained about fundamental processes in the A. nidulans model system is directly applicable to fungi used in biotechnology in the food, beverage, enzyme and pharmaceutical production industries, and to fungal pathogens. Since the fungal genes that form the basis of this project are conserved in higher eukaryotes including humans, the knowledge will be transferable to these systems. A further benefit that cannot be overstated is the research education and training opportunities provided.
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Meiotic recombination in Neurospora crassa: a model for the process in humans and other multicellular eukaryotes. Genes are shuffled by recombination during meiosis in the sexual cycle of higher organisms. This is best understood in yeast. Our findings show Neurospora recombination differs from yeast recombination. It is more tolerant of sequence mismatch, differs in the relative frequencies of gene conversion and crossing over, has frequently interrupted conversion tracts and has transacting ge ....Meiotic recombination in Neurospora crassa: a model for the process in humans and other multicellular eukaryotes. Genes are shuffled by recombination during meiosis in the sexual cycle of higher organisms. This is best understood in yeast. Our findings show Neurospora recombination differs from yeast recombination. It is more tolerant of sequence mismatch, differs in the relative frequencies of gene conversion and crossing over, has frequently interrupted conversion tracts and has transacting genes controlling recombination hotspot activity. We propose to genetically dissect Neurospora recombination which appears to be a closer model for recombination in humans and other higher eukaryotes, where understanding recombination can assist control of genetic disease, efficient breeding in agriculture and our understanding of evolution.Read moreRead less
Defining the earliest events in lymphatic vasculature formation from veins. Vascular system development is one of the earliest events that occurs in the embryo. The entire lymphatic vascular system forms from the embryo’s early veins. This project aims to define the earliest molecular and cellular changes essential to form an entire second vessel network from just a few precursor cells in the embryo. The project aims to utilise zebrafish and mouse embryos to greatly expand knowledge in the forma ....Defining the earliest events in lymphatic vasculature formation from veins. Vascular system development is one of the earliest events that occurs in the embryo. The entire lymphatic vascular system forms from the embryo’s early veins. This project aims to define the earliest molecular and cellular changes essential to form an entire second vessel network from just a few precursor cells in the embryo. The project aims to utilise zebrafish and mouse embryos to greatly expand knowledge in the formation of this essential vertebrate tissue. Ultimately, this is expected to provide new knowledge in stem and precursor cell differentiation, the evolution of complex organ systems and tissue formation. Outcomes may impact on future biotechnology in the areas of tissues engineering, stem cell differentiation and regeneration.Read moreRead less
Small is beautiful: Did gene-rich regions of mammal chromosomes evolve from microchromosomes? Most birds and reptile genomes feature many tiny microchromosomes. These are not junk, as previously thought, but contain most of the genes. Mammals lack microchromosomes, but contain gene-rich regions with similar attributes. We suggest that microchromosomes originated by genome duplication, and evolved into the gene-rich regions of mammalian chromosomes. We will test this hypothesis by comparing seque ....Small is beautiful: Did gene-rich regions of mammal chromosomes evolve from microchromosomes? Most birds and reptile genomes feature many tiny microchromosomes. These are not junk, as previously thought, but contain most of the genes. Mammals lack microchromosomes, but contain gene-rich regions with similar attributes. We suggest that microchromosomes originated by genome duplication, and evolved into the gene-rich regions of mammalian chromosomes. We will test this hypothesis by comparing sequences and genes in microchromosomes of birds, reptiles and monotremes. This will clarify the origin and evolution of the ?microgenome?, establish its suitability as a model for vertebrate genome organisation, and demonstrate whether microchromosomes are the ancestors of the gene-rich regions of mammalian chromosomes.Read moreRead less
A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to ....A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to explore this hypothesis and to identify the signalling molecules. We will also investigate our novel finding that a specific Ras isoform is involved in ERK5 activation. The work will provide new information on signalling pathways.Read moreRead less
A genomic approach to the mechanism of meiotic recombination in Neurospora. Recombination shuffles DNA sequences between homologous chromosomes during the reduction division in the life cycle of higher organisms. Along with mutation, it is a key process in evolution. Understanding of the molecular processes involved in recombination is largely based on yeast, which is intolerant of significant levels of sequence mismatch, limiting the resolution of analyses of normal recombination events. We hav ....A genomic approach to the mechanism of meiotic recombination in Neurospora. Recombination shuffles DNA sequences between homologous chromosomes during the reduction division in the life cycle of higher organisms. Along with mutation, it is a key process in evolution. Understanding of the molecular processes involved in recombination is largely based on yeast, which is intolerant of significant levels of sequence mismatch, limiting the resolution of analyses of normal recombination events. We have shown that Neurospora, like other less tractable multicellular eukaryotes, is tolerant of sequence mismatch, allowing high resolution analysis of individual recombination events. This project will build on fundamental advances we have already made in understanding how recombination occurs.Read moreRead less