Cellular determinants of retrotransposition. This project aims to understand the processes that control retrotransposition in a genome. Transposable elements make up more than 50% of human genomes. The accumulation of retrotransposons through millions of years of evolution has shaped the genomes of all eukaryotic organisms, including humans. Researchers have elucidated mechanisms the host uses to defend the genome against insertional mutagenesis by retrotransposons, but the cellular machinery an ....Cellular determinants of retrotransposition. This project aims to understand the processes that control retrotransposition in a genome. Transposable elements make up more than 50% of human genomes. The accumulation of retrotransposons through millions of years of evolution has shaped the genomes of all eukaryotic organisms, including humans. Researchers have elucidated mechanisms the host uses to defend the genome against insertional mutagenesis by retrotransposons, but the cellular machinery and genomic environments needed for retrotransposition are undefined. This project aims to use models to uncover the mechanisms that control retrotransposition. This is expected to reveal more about human origins.Read moreRead less
A Genomic analysis of macrophage differentiation: Epigenetic factors that determine transcriptional choices in a lineage dependant manner. Our genetic information is fundamental to who we are, how we develop, & how we age. This project will build the research capacity of Australia's genome sciences, providing an analytical framework to describe & study the many products expressed from any single gene and to assess the function of genetic variation & test genome regulatory events. An immediate ou ....A Genomic analysis of macrophage differentiation: Epigenetic factors that determine transcriptional choices in a lineage dependant manner. Our genetic information is fundamental to who we are, how we develop, & how we age. This project will build the research capacity of Australia's genome sciences, providing an analytical framework to describe & study the many products expressed from any single gene and to assess the function of genetic variation & test genome regulatory events. An immediate outcome is a better understanding of the regulation of our immune system. This approach will fuel the discovery of new signalling molecules & their effects on a population of cells, & likewise provides a novel approach to study the dysregulation of cell signalling pathways.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
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
A new statistical framework to understand the biological basis of Ankylosing Spondylitis and other complex diseases. Ankylosing Spondylitis (AS) is a highly heritable and common inflammatory arthritis which causes stiffness and progressive fusion of the spine, decreased quality of life and reduced lifespan. There is no known cure for the condition. This project aims to identify genes and biological pathways involved in AS pathogenesis using a new statistical framework that will be applied to tho ....A new statistical framework to understand the biological basis of Ankylosing Spondylitis and other complex diseases. Ankylosing Spondylitis (AS) is a highly heritable and common inflammatory arthritis which causes stiffness and progressive fusion of the spine, decreased quality of life and reduced lifespan. There is no known cure for the condition. This project aims to identify genes and biological pathways involved in AS pathogenesis using a new statistical framework that will be applied to thousands of individuals with the disease. This project will improve understanding of the underlying mechanisms involved in AS pathophysiology, inform development of new drug treatments for the condition, and create a powerful new statistical approach that can be used to identify biological pathways which are important in the pathogenesis of other complex diseases.Read moreRead less
How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, ....How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, this project expects to provide insights into non-coding regulatory element reprogramming and control of immune cell function and memory with implications for understanding general cellular differentiation.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160100755
Funder
Australian Research Council
Funding Amount
$371,000.00
Summary
Evolution of genome architecture. The project aims to understand how changes to genome architecture over evolutionary time are linked to the diversity of animal morphology. Our genome sequence is arranged into higher order structures that enable coordinated gene expression. The appropriate expression of genes in time and space is necessary to produce the multitude of cell types that make up a multicellular organism. Yet, to date, genome topology is poorly explored, especially between species. Th ....Evolution of genome architecture. The project aims to understand how changes to genome architecture over evolutionary time are linked to the diversity of animal morphology. Our genome sequence is arranged into higher order structures that enable coordinated gene expression. The appropriate expression of genes in time and space is necessary to produce the multitude of cell types that make up a multicellular organism. Yet, to date, genome topology is poorly explored, especially between species. The project involves comparisons of the 3D structure of genomes in divergent species. These findings are expected to inform the underlying principles of gene regulation in animals and species evolution.Read moreRead less
Mapping recombination blocks in Brassica. DNA technology provides new ways to study genomes. Understanding how the genome behaves during plant breeding will help design strategies for the breeding and selection of improved crop plants.
Evolution and function of fragmented animal mitochondrial genomes. This project will reveal why animal mitochondrial genomes are in pieces, and how fragmented mitochondrial genomes evolve and function. This project will discover whether or not fragmented mitochondrial genomes have functional advantages. Knowledge generated from this project will lead to new approaches to mitochondrial genetic diseases in humans.
Towards a new understanding of the reproductive system. The proposed analysis of the reproductive system will provide important new knowledge of gene regulation driving organ development. The insights and technologies developed in this program will be widely applicable in biotechnological and pharmacogenomic research in Australia and worldwide, and assert Australia's leadership in this area of research.