Mathematical Modelling of the Mechanobiology of Arterial Plaque Growth. Plaque growth is a chronic inflammatory response induced by the interactions between endothelial cells, lipids, monocytes/macrophages, smooth muscle cells and platelets in the arteries. It involves many different biological processes, such as lipid deposition, inflammation and angiogenesis, and their interactions with the microcirculation. To understand the underlying mechanobiology, we propose to develop a mathematical mode ....Mathematical Modelling of the Mechanobiology of Arterial Plaque Growth. Plaque growth is a chronic inflammatory response induced by the interactions between endothelial cells, lipids, monocytes/macrophages, smooth muscle cells and platelets in the arteries. It involves many different biological processes, such as lipid deposition, inflammation and angiogenesis, and their interactions with the microcirculation. To understand the underlying mechanobiology, we propose to develop a mathematical model to interpret plaque growth by integrating these dynamic biological processes. It will offer a systematic rational understanding of plaque growth. New models will be provided to better interpret biological data and contribute to our knowledge in quantifying complex biological mechanisms during growth and development.Read moreRead less
Understanding how an old heart gets stiff. Aging is accompanied by a stiffening of the heart and reduced function, which is accelerated by cardiovascular disease and leads to heart failure. How the heart stiffens is poorly understood. A new mechanism is proposed here, involving structural membrane proteins (termed caveolae and cavins) and a signalling molecule (nitric oxide). The current research aims to unravel the interplay between cardiac cells and these proteins/signals to cause stiffness an ....Understanding how an old heart gets stiff. Aging is accompanied by a stiffening of the heart and reduced function, which is accelerated by cardiovascular disease and leads to heart failure. How the heart stiffens is poorly understood. A new mechanism is proposed here, involving structural membrane proteins (termed caveolae and cavins) and a signalling molecule (nitric oxide). The current research aims to unravel the interplay between cardiac cells and these proteins/signals to cause stiffness and to determine whether this process governs normal aging of the heart. This work will advance understanding of how heart function is determined and reveal how the human heart changes with normal aging. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220101226
Funder
Australian Research Council
Funding Amount
$423,000.00
Summary
Testing Effects of Environmental Exposures on Subsequent Human Generations. This project aims to develop new statistical models to determine how environmental exposures in pregnancy, such as smoking, alcohol consumption and diet, can impact the first and second generations of children. The project will fill a void in unbiased tools to disentangle genetic and environmental components in the inheritance of complex traits, and will be the first to determine objectively if and how effects from envir ....Testing Effects of Environmental Exposures on Subsequent Human Generations. This project aims to develop new statistical models to determine how environmental exposures in pregnancy, such as smoking, alcohol consumption and diet, can impact the first and second generations of children. The project will fill a void in unbiased tools to disentangle genetic and environmental components in the inheritance of complex traits, and will be the first to determine objectively if and how effects from environmental exposures can be inherited. Through international collaborations and advanced interdisciplinary approaches, this project will generate new knowledge in the emerging field of multigenerational inheritance to drive the future design of interventions and influence positive behaviours during pregnancy.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE200100425
Funder
Australian Research Council
Funding Amount
$409,364.00
Summary
Genetic and Molecular Consequences of Non-Random Mating in Humans. This project aims to develop and apply novel statistical methods to quantify the effects on a large number of complex traits of two forms of non-random mating in humans, that is inbreeding and assortative mating. The innovation in this proposal lies in integrating multi-level phenotypes with next-generation sequencing data collected in more than half a million study participants. Expected outcomes of this research include advance ....Genetic and Molecular Consequences of Non-Random Mating in Humans. This project aims to develop and apply novel statistical methods to quantify the effects on a large number of complex traits of two forms of non-random mating in humans, that is inbreeding and assortative mating. The innovation in this proposal lies in integrating multi-level phenotypes with next-generation sequencing data collected in more than half a million study participants. Expected outcomes of this research include advanced analytical methods to perform this integration and dissection of the biological consequences of non-random mating in humans at an unprecedented phenotypically detailed scale. The benefit of this project will be to identify new drivers of mate choice that can contribute to economic, health and social inequalities. 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
From shape to function: how structured RNA defines insect flaviviruses. The goal of this project is to obtain an understanding of how insect-specific flaviviruses (ISFs) utilise viral noncoding RNAs to enable their replication in mosquitoes. These viruses only replicate in mosquitoes, and not in humans or animals. They can be employed as the biocontrol agents for mosquito-borne diseases as they make mosquitoes incapable of disease transmission. However, it is currently unknown how exactly insect ....From shape to function: how structured RNA defines insect flaviviruses. The goal of this project is to obtain an understanding of how insect-specific flaviviruses (ISFs) utilise viral noncoding RNAs to enable their replication in mosquitoes. These viruses only replicate in mosquitoes, and not in humans or animals. They can be employed as the biocontrol agents for mosquito-borne diseases as they make mosquitoes incapable of disease transmission. However, it is currently unknown how exactly insect-specific flaviviruses affect mosquitoes and this information is vital for informed design of ISF-based interventions. The project will generate new knowledge on functions of noncoding RNAs in ISFs that are hypothesised to have immunomodulatory role in mosquitoes. It will also train students and ECRs.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
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
FastStack - evolutionary computing to stack desirable alleles in wheat. This project aims to investigate rapid development of new, high-yielding wheat varieties with appropriate disease resistance. An emerging challenge in wheat breeding is how to stack desirable alleles for disease resistance, drought, and end-use quality into new varieties with high yielding backgrounds in the shortest time. As the number of known desirable alleles for these traits increases, the number of possible crossing c ....FastStack - evolutionary computing to stack desirable alleles in wheat. This project aims to investigate rapid development of new, high-yielding wheat varieties with appropriate disease resistance. An emerging challenge in wheat breeding is how to stack desirable alleles for disease resistance, drought, and end-use quality into new varieties with high yielding backgrounds in the shortest time. As the number of known desirable alleles for these traits increases, the number of possible crossing combinations that need to be considered increases. This project aims to use evolutionary computing with speed breeding and genomic selection, in the partners breeding program, to address this challenge. Potential outcomes will lead to more profitable wheat varieties for Australian growers, and expanded exports to high value markets that require quality grain.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