Discovery Early Career Researcher Award - Grant ID: DE230101315
Funder
Australian Research Council
Funding Amount
$461,154.00
Summary
The dynamic interplay between the matrix and cell fate in developing heart. Malformations in the developing heart can lead to catastrophic defects and embryonic loss. The valves play a critical role in blood flow regulation and are made of a stratified matrix that is laid down early in development. This project aims to determine how the cellular fate of the early valve cells establish the layered matrix and in turn how the matrix can influence cell fate by utilising a multi-omics approach to ide ....The dynamic interplay between the matrix and cell fate in developing heart. Malformations in the developing heart can lead to catastrophic defects and embryonic loss. The valves play a critical role in blood flow regulation and are made of a stratified matrix that is laid down early in development. This project aims to determine how the cellular fate of the early valve cells establish the layered matrix and in turn how the matrix can influence cell fate by utilising a multi-omics approach to identify unique cell populations and integrate transcriptional and protein changes during matrix disruption. This project expects to generate fundamental knowledge on how matrix structure can influence cell fate in the valves and will advance Australia's knowledge base and research capabilities in developmental biology.Read moreRead less
Transitions between modes of sex-determination in a changing world. Sex-determination controls the largest variation within animals—the division into males and females. While the different systems of sex-determination—involving genetic or environmental control—are fairly well understood, transitions between these systems remain enigmatic in evolutionary biology. This project aims to address this gap by revealing the molecular change required to transition between systems, using one of only two k ....Transitions between modes of sex-determination in a changing world. Sex-determination controls the largest variation within animals—the division into males and females. While the different systems of sex-determination—involving genetic or environmental control—are fairly well understood, transitions between these systems remain enigmatic in evolutionary biology. This project aims to address this gap by revealing the molecular change required to transition between systems, using one of only two known lizard species exhibiting both genetic and temperature control of sex. This knowledge will have important implications for species conservation, facilitating predictions of highly biased sex ratios under climate change, plus potential commercial applications for species where production of one sex is favoured.Read moreRead less
Unravelling the contributions of Denisovan DNA to the peoples of Oceania. This project aims to investigate the impact gene flow from Denisovans, an archaic hominin species, has had on individuals from Papua New Guinea and eastern Indonesia. These people owe up to 5% of their genomes to these mysterious ancestors, but the repercussions of this finding remain poorly understood. In order to identify the biological contributions these fragments of DNA make to the individuals who carry them, this pro ....Unravelling the contributions of Denisovan DNA to the peoples of Oceania. This project aims to investigate the impact gene flow from Denisovans, an archaic hominin species, has had on individuals from Papua New Guinea and eastern Indonesia. These people owe up to 5% of their genomes to these mysterious ancestors, but the repercussions of this finding remain poorly understood. In order to identify the biological contributions these fragments of DNA make to the individuals who carry them, this project aims to combine anthropological genetics with cutting-edge functional genomics in a pioneer multidisciplinary approach. Ultimately, this project may transform our understanding of both the population and evolutionary pressures that have acted upon these groups in the past 50,000 years.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
Development of efficient CRISPR gene drives in mice. This project aims to generate new tools for vertebrate pest management through development of cutting-edge gene drive technology in mice. Vertebrate pests cost Australia over $1 billion each year in agricultural losses and environmental damage and novel strategies are required to tackle this challenge. Newly developed “gene drives”, which can rapidly spread through populations, have enormous potential for the sustained management and even erad ....Development of efficient CRISPR gene drives in mice. This project aims to generate new tools for vertebrate pest management through development of cutting-edge gene drive technology in mice. Vertebrate pests cost Australia over $1 billion each year in agricultural losses and environmental damage and novel strategies are required to tackle this challenge. Newly developed “gene drives”, which can rapidly spread through populations, have enormous potential for the sustained management and even eradication of pests. This project aims to develop gene drive technology in mice as a prototypical vertebrate pest species. The project will potentially deliver valuable tools that directly impact Australia’s Science and Research Priority on Food.Read moreRead less
Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput ge ....Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput genomics. The expected outcomes will overturn our current view on enhancer evolution and reposition our understanding of how enhancers are functionally encoded in the genome. The work is an important contribution to understanding cellular complexity and species evolution with wide-ranging impact in genetics.Read moreRead less
Can parasites cause host population divergence? . Parasites have been proposed to be drivers of population divergence, and ultimately speciation, yet the dynamics of this process are not well understood. This project will utilise new genomic techniques, novel hybrid zone analyses, and data on mate choice, to investigate the hypothesis that parasites drive population divergence through an interaction with immune response genes in the sleepy lizard Tiliqua rugosa. This species provides an unpreced ....Can parasites cause host population divergence? . Parasites have been proposed to be drivers of population divergence, and ultimately speciation, yet the dynamics of this process are not well understood. This project will utilise new genomic techniques, novel hybrid zone analyses, and data on mate choice, to investigate the hypothesis that parasites drive population divergence through an interaction with immune response genes in the sleepy lizard Tiliqua rugosa. This species provides an unprecedented system, backed by 37 years of long term host-parasite and behavioural data, and recent genetic analyses. This project intends to produce significant data to allow an examination of the early stages of host-parasite evolution in action, providing novel insights into the speciation process. 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
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
Visualising chromatin changes in 3 dimensions: super to ultra resolution. Packaging of genomic information into the nucleus of a cell necessitates the formation of tightly compacted and highly organized genomic structures within the nucleus, a configuration that is inherently repressive for gene transcription. Hence, mechanisms that alter the spatial organisation of DNA are critical to enable a variety of genome functions, including DNA transcription. This proposal will utilise novel adaptations ....Visualising chromatin changes in 3 dimensions: super to ultra resolution. Packaging of genomic information into the nucleus of a cell necessitates the formation of tightly compacted and highly organized genomic structures within the nucleus, a configuration that is inherently repressive for gene transcription. Hence, mechanisms that alter the spatial organisation of DNA are critical to enable a variety of genome functions, including DNA transcription. This proposal will utilise novel adaptations of super resolution microscopy to visualise in 3 dimensions how changes in chromatin modifications impact genome spatial organisation within the nucleus, and how this then links to cellular differentiation. This will provide a picture of how spatial organisation within the nucleus supports general cell differentiation.
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