Links between DNA replication and chromosome end maintenance. This project aims to increase knowledge of the way in which cells maintain their genomes, including the ends of their chromosomes, to enable their own survival. The ends of chromosomes (telomeres) are essential for survival and proliferation of the cells of most organisms. This project aims to determine the molecular details of a recently discovered link between telomere maintenance and the way cells maintain the integrity of their ge ....Links between DNA replication and chromosome end maintenance. This project aims to increase knowledge of the way in which cells maintain their genomes, including the ends of their chromosomes, to enable their own survival. The ends of chromosomes (telomeres) are essential for survival and proliferation of the cells of most organisms. This project aims to determine the molecular details of a recently discovered link between telomere maintenance and the way cells maintain the integrity of their genome. This is likely to lead to increased understanding of the fundamental biological process of genome maintenance, representing a significant scientific advance. The project expects to have far-reaching implications for biotechnology applications that require the survival of cells.Read moreRead less
The Role Of Heterochromatin In Regulating Cellular Proliferation And Development
Funder
National Health and Medical Research Council
Funding Amount
$504,000.00
Summary
Fundamental to the development of a multicellular organism is that for each cell type performing a specialised function, a different set of genes are turned on with the remainder being shut off. One of the most significant unanswered questions in biology is how a cell-type specific gene expression profile is established during early development. The answer to this question has important implications in understanding normal and abnormal cellular processes. Gene expression in a cell occurs in the ....Fundamental to the development of a multicellular organism is that for each cell type performing a specialised function, a different set of genes are turned on with the remainder being shut off. One of the most significant unanswered questions in biology is how a cell-type specific gene expression profile is established during early development. The answer to this question has important implications in understanding normal and abnormal cellular processes. Gene expression in a cell occurs in the nucleus where genes are stored. In the nucleus, DNA is not in a free form but is covered with an equivalent weight of protein (histones) to form a structure known as chromatin. It has become clear that the chromatin structure encompassing a gene is the critical factor that determines whether a gene is expressed or silenced. We propose that developmental and cell-type specific mechanisms operate in a cell to assemble genes into highly specialised chromatin structures that permit (euchromatin) or restrict (heterochromatin) gene expression. In other words, the genome of each different cell type is organised into a unique and dynamic chromatin pattern and this pattern determines the gene expression profile. This investigation will show that the critical cellular mechanism that determines the chromatin pattern for a particular cell type is the regulation of the quantity and quality of heterochromatin. Specifically, we will demonstrate that this is achieved, in a developmental and tissue specific manner, by changing the make-up of chromosomal domains through the replacement of histone proteins with specialised forms of histones called variants . In addition, we will expose a new mechanism of how heterochromatin formation controls the rate of cellular proliferation. This information will provide new insights into how gene expression profiles are established at precise times in early development, and offer a new strategy to inhibit the proliferation of cancer cells.Read moreRead less
The balance between cell division and programmed cell death is crucial for normal development, maintenance of homeostasis, and immune system function. Inappropriately regulated cell death contributes to the pathogenesis of a wide variety of human diseases including neurodegenerative disorders, autoimmune syndromes and several forms of cancer. Death receptors such as Fas and TNFR1 are cell-surface sensors that trigger cellular destruction by apoptosis in response to specific extracellular death s ....The balance between cell division and programmed cell death is crucial for normal development, maintenance of homeostasis, and immune system function. Inappropriately regulated cell death contributes to the pathogenesis of a wide variety of human diseases including neurodegenerative disorders, autoimmune syndromes and several forms of cancer. Death receptors such as Fas and TNFR1 are cell-surface sensors that trigger cellular destruction by apoptosis in response to specific extracellular death signals. Recent studies have demonstrated that the mechanisms of signal transduction through Fas and TNFR1 differ significantly, however, they both require the adaptor protein FADD to induce apoptosis. In this study we will elucidate the molecular basis of the interactions between FADD and its binding partners using biochemical and biophysical studies. This research will improve our understanding of death receptor-induced apoptosis and the differences in signalling mechanisms. A detailed knowledge of these aspects of death receptor signalling is of significance because they represent critical regulatory steps that could be useful for targeted interventions.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE200100584
Funder
Australian Research Council
Funding Amount
$424,636.00
Summary
DNA Replication Stress: Characterizing ground zero for genomic instability. The overarching goal of this research is to gain insights into key underlying molecular causes of, and responses to, DNA replication stress - one of the most fundamental biological processes enabling life as we know it. I will use advanced interdisciplinary imaging techniques to directly visualize DNA replication stress structures within cells in order to better understand how cells stop this stress from progressing into ....DNA Replication Stress: Characterizing ground zero for genomic instability. The overarching goal of this research is to gain insights into key underlying molecular causes of, and responses to, DNA replication stress - one of the most fundamental biological processes enabling life as we know it. I will use advanced interdisciplinary imaging techniques to directly visualize DNA replication stress structures within cells in order to better understand how cells stop this stress from progressing into DNA damage. Insights into these processes will have the potential to improve preventative and therapeutic approaches to diseases such as cancer and neurodegeneration. Read moreRead less
The Regulatory Network of Histone Methylating and Demethylating Enzymes. This project aims to discover how cells regulate histone methylation enzymes. This process ultimately affects which genes can be turned on or off inside cells; something which is central to growth and development in all animals, all plants and some microbes. Expected outcomes include new knowledge on the regulation of histone methylation, improved techniques for the study of this process and enhanced capacity for internatio ....The Regulatory Network of Histone Methylating and Demethylating Enzymes. This project aims to discover how cells regulate histone methylation enzymes. This process ultimately affects which genes can be turned on or off inside cells; something which is central to growth and development in all animals, all plants and some microbes. Expected outcomes include new knowledge on the regulation of histone methylation, improved techniques for the study of this process and enhanced capacity for international collaboration. New avenues for the artificial regulation of genes may also emerge for synthetic epigenetics. The project should provide significant new findings for the research community, generate research citations and contribute to a highly skilled workforce by the training of staff and students.
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Complexities of the mitochondrial transcriptome. This project aims to understand mitochondrial gene expression and energy production. Energy production is important for living things to grow and develop. In mammals, the mitochondria, the energy producing “powerhouses of the cell”, contain their own genetic assembly instructions. This project aims to understand these genetic instructions, revealing how genes control energy production. This project will characterise the genetic instructions, the m ....Complexities of the mitochondrial transcriptome. This project aims to understand mitochondrial gene expression and energy production. Energy production is important for living things to grow and develop. In mammals, the mitochondria, the energy producing “powerhouses of the cell”, contain their own genetic assembly instructions. This project aims to understand these genetic instructions, revealing how genes control energy production. This project will characterise the genetic instructions, the mitochondrial transcriptome and the proteins that control them. These advances are expected to provide a mechanistic understanding of how gene expression responds to changes in cellular energy demands. This knowledge will generate new biotechnological tools for Australian science and will have important long-term implications for improving agriculture and medicineRead moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210100398
Funder
Australian Research Council
Funding Amount
$448,365.00
Summary
The Life And Death Of Plant Genes. My recent work has demonstrated that in contrast to animal genes, many plant genes show presence/absence variation within a species, with associated trait variation. In this project, I will explore models of gene birth and death by comparing genomes of Brassicaceae, including the model Arabidopsis and Brassica crop species. By comparing many genomes I will learn how new genes were born. I will build models that predict the likelihood of gene loss based on a gen ....The Life And Death Of Plant Genes. My recent work has demonstrated that in contrast to animal genes, many plant genes show presence/absence variation within a species, with associated trait variation. In this project, I will explore models of gene birth and death by comparing genomes of Brassicaceae, including the model Arabidopsis and Brassica crop species. By comparing many genomes I will learn how new genes were born. I will build models that predict the likelihood of gene loss based on a gene’s physical environment, function, and expression. The project will build on our understanding of plant genetic diversity. Expected outcomes of this research include the identification of key genomic elements in gene birth and loss and support strategies to improve plant cultivars.Read moreRead less
Glycan-based prebiotic approaches to increase food safety in Australia. Since the launch of the first Australian Animal Sector National Antimicrobial Resistance Plan (2018) several approaches have been suggested to reduce the use antibiotics in agriculture, however no alternatives to antibiotics have been suggested or trialled. In this proposal we aim to develop a novel glycan-based prebiotic strategy to reduce Campylobacter jejuni colonisation in chicken and poultry by disrupting important glyc ....Glycan-based prebiotic approaches to increase food safety in Australia. Since the launch of the first Australian Animal Sector National Antimicrobial Resistance Plan (2018) several approaches have been suggested to reduce the use antibiotics in agriculture, however no alternatives to antibiotics have been suggested or trialled. In this proposal we aim to develop a novel glycan-based prebiotic strategy to reduce Campylobacter jejuni colonisation in chicken and poultry by disrupting important glycan-glycan interactions. Outcomes of this proposal is a cost-effective antibiotic- and vaccine-independent animal feed supplement strategy that will decrease the risk of human food-borne illness and therefore promoting food safety and public health in Australia. Read moreRead less
One of the most amazing engineering achievements in nature is how over 2 meters of genetic material (DNA) can be compacted and squeezed nearly a million times to fit into a human cell. The remarkable structure that achieves this is the chromosome. Fundamental to the survival of a multicellular organism is that the chromosome is stably maintained throughout out the life of an organism. For example, defects in maintaining chromosome stability can lead to aneuploidy (cells with an abnormal number o ....One of the most amazing engineering achievements in nature is how over 2 meters of genetic material (DNA) can be compacted and squeezed nearly a million times to fit into a human cell. The remarkable structure that achieves this is the chromosome. Fundamental to the survival of a multicellular organism is that the chromosome is stably maintained throughout out the life of an organism. For example, defects in maintaining chromosome stability can lead to aneuploidy (cells with an abnormal number of chromosomes), a feature exhibited by many forms of cancer. This packaging of genomic DNA that produces a chromosome is achieved by a complex scheme of folding. At the first level, DNA is first wrapped around a mixture of proteins (called histones) to form a complete unit known as a nucleosome. About 30 million of these building blocks are required in every human cell to compact our DNA. Higher, more complicated levels of organization exist in which a linear array of nucleosomes fold to various extents to form distinct functional and structural domains. Importantly, specialised chromosomal domains, like the telomere and centromere, are assembled that keep the ends of the chromosomes stable and enable a chromosome to copy itself every time our cells divide and grow, respectively. How a chromosome is divided into these different compartments remains a mystery. This investigation will show that a key cellular mechanism that determines how the chromosome is organised into stable domains is by changing the make-up of chromosomal domains through the replacement of histone proteins with specialised forms of histones called variants . These histone variants control the way a linear array of nucleosomes fold into complex three-dimensional structures to perform a specialised function. This fundamental research will provide important new information on how chromosomes become unstable in cancer. It will also enable new strategies, which stabilise the chromosome, to be explored.Read moreRead less