Neurogenesis in bilateral larval and radial adult body plans: identification of echinoderm homologues of the chordate central nervous system. The modern synthesis of embryology and gene expression studies, as undertaken in this project with sea stars, is a major way forward to achieve advances in our understanding of animal evolution and generate new insights into the mystery that surrounds the origin of our own phylum, the Chordata. This project utilises life history diversity in species that a ....Neurogenesis in bilateral larval and radial adult body plans: identification of echinoderm homologues of the chordate central nervous system. The modern synthesis of embryology and gene expression studies, as undertaken in this project with sea stars, is a major way forward to achieve advances in our understanding of animal evolution and generate new insights into the mystery that surrounds the origin of our own phylum, the Chordata. This project utilises life history diversity in species that are unique Australian fauna. Extreme life history diversity as seen in these sea stars is unparalleled on a global scale and provides an important resource to generate new discoveries on the processes underlying evolution in the sea and enhance our understanding of marine systems. Read moreRead less
Regulation of mammalian differentiation by methylation of histones and transcription factors. The objective of this proposal is to examine the functional role of arginine and lysine methylation during skeletal muscle differentiation. Differentiation, i.e the acquisition of a specific phenotype, is the biological end point of the ?Genome-Phenome? transition. Specifically, the proposal will seek to understand the role of protein methylation in the control of tissue specific gene expression and ce ....Regulation of mammalian differentiation by methylation of histones and transcription factors. The objective of this proposal is to examine the functional role of arginine and lysine methylation during skeletal muscle differentiation. Differentiation, i.e the acquisition of a specific phenotype, is the biological end point of the ?Genome-Phenome? transition. Specifically, the proposal will seek to understand the role of protein methylation in the control of tissue specific gene expression and cell signaling during differentiation. Key areas of study in the ARC priority area of Genome-Phenome research. We will test the hypothesis that the activity/function of the hierarchical myogenic transcription factors and cofactors that control skeletal myogenesis is influenced by protein methylation.Read moreRead less
Noncoding RNAs As Prognostic Markers And Therapeutic Targets In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$550,283.00
Summary
Normal human development involves a symphony of genetic changes that control the growth and differentiation of different types of cells during embryogenesis. For many years it has been assumed that most genetic information is transacted by proteins, and that the remaining 98% of the human genome that does not encode proteins was (apart from a limited amount of associated regulatory elements) largely non-functional evolutionary junk. However, this may not be the case. Recent results from our labo ....Normal human development involves a symphony of genetic changes that control the growth and differentiation of different types of cells during embryogenesis. For many years it has been assumed that most genetic information is transacted by proteins, and that the remaining 98% of the human genome that does not encode proteins was (apart from a limited amount of associated regulatory elements) largely non-functional evolutionary junk. However, this may not be the case. Recent results from our laboratory and others have shown that most of our genome and that of other mammals is actually expressed as noncoding RNA, which appears to be developmentally regulated. These RNAs (of which there appear to be tens of thousands, well outnumbering the protein-coding mRNAs) have been referred to as the hidden layer or dark matter of our genome, as they have barely been studied, but appear to play a central role in both normal and abnormal development in humans. There is now increasing evidence that many noncoding RNAs, including small regulatory RNAs called microRNAs, are perturbed in cancer and that these perturbations may be directly involved in, and be an accurate indicator of, cancer state and the direction of cancer progression. If this is true we need to understand the expression and functions of these RNAs in order to develop better diagnostics and perhaps powerful new therapeutics for cancer, based on RNA technology and generic delivery systems. This project will explore the patterns of noncoding RNA expression in normal breast development and in breast cancer, to identify those RNAs that direct or accompany the differentiation of these tissues, and to test the effects of interfering with their expression on these processes. These foundation studies lie at the leading edge of a new understanding of human genetics and cancer, and will provide a platform for future applications in medicine that utilize this information and understanding.Read moreRead less
The role of the neuronal Hu proteins in the regulation of the BMP signalling pathway. We aim to understand the critical decision of a neural progenitor to commit to becoming a neuron. The BMP signalling pathway is central in this decision. Neural progenitors appear to become insensitive to BMP signals, and this lack of signalling leads to neuronal differentiation. We hypothesise that neuronal identity is regulated by an unusual genetic switch- the translational regulation by the neuronal Hu pr ....The role of the neuronal Hu proteins in the regulation of the BMP signalling pathway. We aim to understand the critical decision of a neural progenitor to commit to becoming a neuron. The BMP signalling pathway is central in this decision. Neural progenitors appear to become insensitive to BMP signals, and this lack of signalling leads to neuronal differentiation. We hypothesise that neuronal identity is regulated by an unusual genetic switch- the translational regulation by the neuronal Hu proteins of two proteins in the BMP pathway. Verification of a post-transcriptional regulatory mechanism for cell fate determination would be a major discovery, and may prompt investigation of how to harness the neuron-inducing function of the Hu proteins to address the therapeutic need for new neurons in neurologic diseases.Read moreRead less
Origin of multicellularity in animals: identification and analysis of intercellular signalling pathways in a basal metazoan, the demosponge Reniera. The Reniera genome project is a multi-million dollar collaboration between JGI (US-DOE) and Australian scientists that will see the sequencing of the first Australian marine animal by 2006. This project will significantly advance our understanding of the origins of animals and contribute to the reconstruction of creatures that lived over 600 million ....Origin of multicellularity in animals: identification and analysis of intercellular signalling pathways in a basal metazoan, the demosponge Reniera. The Reniera genome project is a multi-million dollar collaboration between JGI (US-DOE) and Australian scientists that will see the sequencing of the first Australian marine animal by 2006. This project will significantly advance our understanding of the origins of animals and contribute to the reconstruction of creatures that lived over 600 million years ago. A major outcome of this reconstruction will be a fundamental understanding of how cells communicate with each other during the process of development to give rise to the diversity of cell types within multicellular animals. This study will also shed light on what happens when cell communication goes astray, as observed in a range of human malignancies, including cancer. Read moreRead less
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
Discovery Early Career Researcher Award - Grant ID: DE200101748
Funder
Australian Research Council
Funding Amount
$410,716.00
Summary
Discovering hidden control elements for crop improvement. Sustainable, productive agricultural processes are essential for tackling the challenges of tomorrow’s world. The ability to optimise beneficial agricultural traits depends on the precise control of genes in a crop plant’s enormous genome. Yet, identifying valuable gene control regions is like looking for needles in a haystack. The location of these regions is often not obvious and current detection technologies are impractically expensiv ....Discovering hidden control elements for crop improvement. Sustainable, productive agricultural processes are essential for tackling the challenges of tomorrow’s world. The ability to optimise beneficial agricultural traits depends on the precise control of genes in a crop plant’s enormous genome. Yet, identifying valuable gene control regions is like looking for needles in a haystack. The location of these regions is often not obvious and current detection technologies are impractically expensive and intensive. This project aims to develop a new technology that is expected to facilitate rapid and cost-effective discovery of all the control regions in a genome, enhancing our understanding of crop genomes and unlocking new avenues for agricultural improvement, food security and economic stability.Read moreRead less
Early animal evolution: reconstructing the last common metazoan ancestor through the analysis of developmental and structural genes in sponges. All animals, from the simplest invertebrates to humans, arose from a common ancestor. Reconstruction of this ancestor requires the comparison of metazoan developmental genetic architectures. Here we contribute to this pursuit by studying a phylogenetically and biological appropriate metazoan system - marine sponge embryos and larvae. Using high-throughp ....Early animal evolution: reconstructing the last common metazoan ancestor through the analysis of developmental and structural genes in sponges. All animals, from the simplest invertebrates to humans, arose from a common ancestor. Reconstruction of this ancestor requires the comparison of metazoan developmental genetic architectures. Here we contribute to this pursuit by studying a phylogenetically and biological appropriate metazoan system - marine sponge embryos and larvae. Using high-throughput gene profiling techniques, we will analyse the developmental genetics underlying the sponge body plan. Commonalities shared between sponges and more sophisticated animals are likely to have been present in the "genetic toolkit" of the most ancient metazoan ancestor and, as such, is the genetic foundation from which all animal biodiversity arose.Read moreRead less
Genetic control of plant organ growth. Plants organs, such as leaves and petals, have a distinct size and shape reflecting differences in growth. Despite its importance, very little is known about the mechanisms that regulate growth. The objectives of this proposal are a) to test whether organ growth depends on cell-cell signalling and b) to identifying genes that regulate growth, and to characterize their molecular function.