The genetics of four ancient 'Kings' of Sahul and Sunda. This project aims to recover all the genetic information from four ancient humans. Two of these iconic specimens come from Australia and two from Malaysia. We will sequence the entire DNA (genomes) and proteins (proteome) of Mungo Man (Willandra), the Yidinji King (Cairns), the Deep Skull (Borneo) and the Bewah specimen (Malaysian Peninsula). This will provide a better understanding of the settlement of Australia and new knowledge about th ....The genetics of four ancient 'Kings' of Sahul and Sunda. This project aims to recover all the genetic information from four ancient humans. Two of these iconic specimens come from Australia and two from Malaysia. We will sequence the entire DNA (genomes) and proteins (proteome) of Mungo Man (Willandra), the Yidinji King (Cairns), the Deep Skull (Borneo) and the Bewah specimen (Malaysian Peninsula). This will provide a better understanding of the settlement of Australia and new knowledge about the ancient people of Australasia and their relationship to other human populations worldwide. The research will use cutting-edge methods of DNA and protein sequencing of ancient human material and will provide critical reference genomes / proteomes that will anchor future research.Read moreRead less
Genetic architecture and evolution of complex traits across populations. Most human traits have a genetic component and display substantial diversity within and among populations. How natural selection changes and maintains genetic variation in human traits is a long-standing question in evolution that the proposed project aims to answer. Using innovative statistical methods and largest genomic “big” datasets ever across populations of different ancestral backgrounds, this project expects to gen ....Genetic architecture and evolution of complex traits across populations. Most human traits have a genetic component and display substantial diversity within and among populations. How natural selection changes and maintains genetic variation in human traits is a long-standing question in evolution that the proposed project aims to answer. Using innovative statistical methods and largest genomic “big” datasets ever across populations of different ancestral backgrounds, this project expects to generate new knowledge on the roles of natural selection in shaping the genetic variation in traits and identify key factors that drive the differentiation of human populations. These outcomes will significantly improve our understanding on the evolution of human traits and adaptation of populations to changing environments.Read moreRead less
The origins of Australia's non-Pama-Nyungan speaking people. This project aims to test the likelihood of multiple migrations into Australia before European arrival and determine if the phylogenetic relationships among non-Pama-Nyungan languages is mirrored by their speakers’ genomic phylogenetic relationships. The non-Pama-Nyungan First People of Australia speak an extraordinary number and diversity of Aboriginal languages, but the origins of these languages and the genomic diversity of the peop ....The origins of Australia's non-Pama-Nyungan speaking people. This project aims to test the likelihood of multiple migrations into Australia before European arrival and determine if the phylogenetic relationships among non-Pama-Nyungan languages is mirrored by their speakers’ genomic phylogenetic relationships. The non-Pama-Nyungan First People of Australia speak an extraordinary number and diversity of Aboriginal languages, but the origins of these languages and the genomic diversity of the people who speak them are only now starting to be understood. There is a remarkable concordance between the Pama-Nyungan languages and the genomic diversity of their speakers. This research could show whether genomes change languages or vice versa, or whether they evolve together over time.Read moreRead less
The nature of standing genetic variation. This project aims to expand understanding of the genetic variation underlying phenotypic differences among individuals. The nature of genetic variation has broad consequences across biology, from the detection of causal genetic variants to the adaptation of natural populations. This project will take a novel experimental approach to test several long-standing assumptions about the effects of new mutations on individual traits and their joint pleiotropic ....The nature of standing genetic variation. This project aims to expand understanding of the genetic variation underlying phenotypic differences among individuals. The nature of genetic variation has broad consequences across biology, from the detection of causal genetic variants to the adaptation of natural populations. This project will take a novel experimental approach to test several long-standing assumptions about the effects of new mutations on individual traits and their joint pleiotropic effect on fitness. By expanding our understanding of how mutation, selection and drift interact, this project could provide significant improvements in our understanding of the genetic basis of phenotypes, and our ability to predict phenotypic evolution.Read moreRead less
Characterising inheritance patterns of whole genome DNA methylation. This project aims to characterise epigenetic diversity and inheritance patterns in whole genome sequencing data from a unique human population. The project will employ the well-characterised Norfolk Island genetic isolate, cost-effective whole genome bisulphite sequencing technologies and advanced bioinformatics pipelines and statistical models. It will involve cross-discipline collaboration between human geneticists, epigeneti ....Characterising inheritance patterns of whole genome DNA methylation. This project aims to characterise epigenetic diversity and inheritance patterns in whole genome sequencing data from a unique human population. The project will employ the well-characterised Norfolk Island genetic isolate, cost-effective whole genome bisulphite sequencing technologies and advanced bioinformatics pipelines and statistical models. It will involve cross-discipline collaboration between human geneticists, epigeneticists, statistical geneticists and bioinformaticians. This project will advance our understanding of the interaction of genetics and epigenetics and their relationship to diversity and inheritance in humans.Read moreRead less
Predicting the evolutionary dynamics of adaptation. This project aims to address the question of how we can predict adaptive evolution. The project aims to probe the limits of evolutionary predictions by using a model system of bacterial populations that adapt to the presence of multiple stressors. This will be combined with high-throughput fitness measurements, whole genome sequencing and computer simulations. Anticipated outcomes include novel insights into deep questions regarding the structu ....Predicting the evolutionary dynamics of adaptation. This project aims to address the question of how we can predict adaptive evolution. The project aims to probe the limits of evolutionary predictions by using a model system of bacterial populations that adapt to the presence of multiple stressors. This will be combined with high-throughput fitness measurements, whole genome sequencing and computer simulations. Anticipated outcomes include novel insights into deep questions regarding the structure of fitness landscapes and the repeatability, predictability and contingency of adaptive evolution. The project is expected to provide significant benefits, informing the development of improved strategies for managing pathogen resistance to antimicrobial drugs.Read moreRead less
Decoding Bacterial Epigenetic Regulation. This project aims to characterise bacterial epigenetic regulation by determining the mechanism of action and impact of bacterial DNA methylation. This project expects to generate new knowledge about fundamental aspects of bacterial gene regulation, using a novel combination of cutting edge DNA and RNA sequencing, proteomic and bioinformatic approaches. The expected outcomes of this project will provide new tools to facilitate the integration of epigenomi ....Decoding Bacterial Epigenetic Regulation. This project aims to characterise bacterial epigenetic regulation by determining the mechanism of action and impact of bacterial DNA methylation. This project expects to generate new knowledge about fundamental aspects of bacterial gene regulation, using a novel combination of cutting edge DNA and RNA sequencing, proteomic and bioinformatic approaches. The expected outcomes of this project will provide new tools to facilitate the integration of epigenomic analysis into genomic studies, exponentially increasing the volume and value of data gathered. This would provide significant future benefits to all academic, biotechnology, agricultural, veterinary and pharmaceutical applications that involve bacterial genomic analysis.Read moreRead less
The impact of Hyaluronic Acid on growth factor signalling and angiogenesis. Blood vessel development is controlled by growth factor signalling. Vessels are attracted by and migrate along growth factor gradients, and this is controlled by the extracellular matrix (ECM). From the zebrafish model, we have identified a novel gene that modulates the ECM, impacting growth factor signalling and vessel development. The project will explore by what mechanism this gene impacts signalling. It will comprehe ....The impact of Hyaluronic Acid on growth factor signalling and angiogenesis. Blood vessel development is controlled by growth factor signalling. Vessels are attracted by and migrate along growth factor gradients, and this is controlled by the extracellular matrix (ECM). From the zebrafish model, we have identified a novel gene that modulates the ECM, impacting growth factor signalling and vessel development. The project will explore by what mechanism this gene impacts signalling. It will comprehensively define where in the embryo it is required and investigate what cofactors it interacts with to perform its function. Using genetic zebrafish and mouse models as well as cell culture models we will investigate the fundamental biology of this gene.Read moreRead less
Visualising genetic mosaicism during development. Genetic diversity is the variation in DNA sequence among individuals. We now know that there are also differences in the DNA sequences of cells within the same individual, known as genetic mosaicism. The aims of this proposal are 1) to develop a system to visualise genetic mosaicism 2) arising during embryonic development and 3) in the brain, driven by mobile DNA activity. The expected outcome of this proposal is an unprecedented understanding of ....Visualising genetic mosaicism during development. Genetic diversity is the variation in DNA sequence among individuals. We now know that there are also differences in the DNA sequences of cells within the same individual, known as genetic mosaicism. The aims of this proposal are 1) to develop a system to visualise genetic mosaicism 2) arising during embryonic development and 3) in the brain, driven by mobile DNA activity. The expected outcome of this proposal is an unprecedented understanding of the scope and consequences of mobile DNA-driven mosaicism. This work will have significant impacts in developmental genetics and neurogenetics, and has the benefit of introducing an innovative experimental system with the potential to spark international scientific collaboration and recognition.Read moreRead less
Dissecting natural variation in sexually dimorphic gene expression. This project aims to understand the origins of sex differences by dissecting heritable variation in sexually dimorphic gene expression. Sexual dimorphism constitutes a large fraction of phenotypic diversity and arises mainly from sex differences in gene expression that permit males and females of a species to escape sexual conflict caused by a shared genome. The project uses multi-population quantitative genetics and allele-spec ....Dissecting natural variation in sexually dimorphic gene expression. This project aims to understand the origins of sex differences by dissecting heritable variation in sexually dimorphic gene expression. Sexual dimorphism constitutes a large fraction of phenotypic diversity and arises mainly from sex differences in gene expression that permit males and females of a species to escape sexual conflict caused by a shared genome. The project uses multi-population quantitative genetics and allele-specific expression assays to merge the studies of sex-specific local adaptation and sexually dimorphic regulatory variation. The project will help to understand how cis- and trans- regulatory factors can affect natural variation differently in males and females, shaping their phenotypic similarities and differences.Read moreRead less