The evolutionary transition from anaerobic to aerobic metabolism. This project aims to find out how life on Earth survived the revolutionary changes when cyanobacteria first released oxygen into the atmosphere. These events led to a transition from anoxic (oxygen-free) to oxic (oxygen-rich) conditions. A comparative genomic view across a series of photosynthetic organisms will be performed at the molecular level with ecological interpretation. Understanding of what metabolic changes occurred in ....The evolutionary transition from anaerobic to aerobic metabolism. This project aims to find out how life on Earth survived the revolutionary changes when cyanobacteria first released oxygen into the atmosphere. These events led to a transition from anoxic (oxygen-free) to oxic (oxygen-rich) conditions. A comparative genomic view across a series of photosynthetic organisms will be performed at the molecular level with ecological interpretation. Understanding of what metabolic changes occurred in response to the shifts in the environment will have wide implications for predicting the evolutionary events that are still occurring today, such as rapidly changing climatic conditions. This fundamental research will enhance Australia's profile in this field.Read moreRead less
Modern reptiles with ancient toxins: the molecular origin and evolution of novel bioactive proteins from squamate dental glands. Animal venoms provide a rich source of novel bioactive proteins, some of which have demonstrated therapeutically useful activities. Through this researcher's unique approach of investigating previously unmapped squamate venom systems, there is potential for the identification of divergent, bioactive proteins. Those already identified by the applicant in the dental gl ....Modern reptiles with ancient toxins: the molecular origin and evolution of novel bioactive proteins from squamate dental glands. Animal venoms provide a rich source of novel bioactive proteins, some of which have demonstrated therapeutically useful activities. Through this researcher's unique approach of investigating previously unmapped squamate venom systems, there is potential for the identification of divergent, bioactive proteins. Those already identified by the applicant in the dental glands of Australian monitor lizard species represent a tremendous opportunity for biodiscovery. Further knowledge in this area will increase medical understandings of bites and aid conservation measures informed by the natural history of these animals.Read moreRead less
Characterisation of heavy metal transport genes in the plant Arabidopsis: potential roles in metal detoxification and accumulation. Plants have considerable potential for the bioremediation ("phytoremediation") of contaminated soils, including soils polluted with heavy metals. Progress has been made in understanding the physiological and biochemical mechanisms by which plants accumulate and detoxify heavy metals. One important aspect of metal detoxification is the transport of metals across cell ....Characterisation of heavy metal transport genes in the plant Arabidopsis: potential roles in metal detoxification and accumulation. Plants have considerable potential for the bioremediation ("phytoremediation") of contaminated soils, including soils polluted with heavy metals. Progress has been made in understanding the physiological and biochemical mechanisms by which plants accumulate and detoxify heavy metals. One important aspect of metal detoxification is the transport of metals across cell membranes. The recently completed genome project for the model plant Arabidopsis has identified a family of genes encoding heavy metal transport proteins. This project aims to investigate the roles of these genes in metal detoxification. In the longer term this knowledge can be applied to the improvement of phytoremediation processes.Read moreRead less
Mechanisms of zinc transport and homeostasis in the plant, Arabidopsis. Zinc-deficiency is one of the most widespread factors limiting crop production and affects many soils of south-east and south-west Australia. Certain zinc-efficient (ZE) crop cultivars are able to grow well under zinc deficient conditions but the genetic basis for ZE is not well understood. Using a model organism such as Arabidopsis to identify genes in plants that are important in zinc transport and homeostasis will ultimat ....Mechanisms of zinc transport and homeostasis in the plant, Arabidopsis. Zinc-deficiency is one of the most widespread factors limiting crop production and affects many soils of south-east and south-west Australia. Certain zinc-efficient (ZE) crop cultivars are able to grow well under zinc deficient conditions but the genetic basis for ZE is not well understood. Using a model organism such as Arabidopsis to identify genes in plants that are important in zinc transport and homeostasis will ultimately allow us to assess whether the homologous genes in crop species are responsible for ZE. This may contribute to more rapid and directed strategies in breeding ZE crop cultivars.Read moreRead less
Defining a role for non-coding RNAs in gonadal sex differentiation. This project aims to increase knowledge in the area of developmental biology, studying how gene regulation by so-called non-coding RNAs contributes to tissue patterning. The project plans to use a unique model system: gonadal development in the chicken embryo. It also plans to use novel molecular approaches that exploit the chicken model to study the role of microRNAs and a long non-coding RNA in patterning the embryonic gonad. ....Defining a role for non-coding RNAs in gonadal sex differentiation. This project aims to increase knowledge in the area of developmental biology, studying how gene regulation by so-called non-coding RNAs contributes to tissue patterning. The project plans to use a unique model system: gonadal development in the chicken embryo. It also plans to use novel molecular approaches that exploit the chicken model to study the role of microRNAs and a long non-coding RNA in patterning the embryonic gonad. The project aims to provide a deeper understanding of how genes operate to control tissue patterning and organogenesis. It may thus inform the field of sex determination specifically, and, more broadly, stem cell biology and tissue engineering.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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882512
Funder
Australian Research Council
Funding Amount
$400,000.00
Summary
Advanced high throughput functional genomics and gene mapping. Infrastructure requested will expand the capacity of researchers in NSW to undertake experiments using state-of-the-art technologies based on the recent advances in genomic and proteomic analysis. It will ensure the retention of leading researchers in the exciting areas of functional genomics and systems biology as contribute to biomolecular research in medicine, agriculture and environmental biology, thereby providing major benefit ....Advanced high throughput functional genomics and gene mapping. Infrastructure requested will expand the capacity of researchers in NSW to undertake experiments using state-of-the-art technologies based on the recent advances in genomic and proteomic analysis. It will ensure the retention of leading researchers in the exciting areas of functional genomics and systems biology as contribute to biomolecular research in medicine, agriculture and environmental biology, thereby providing major benefits to the wider community. The application aims to enhance existing genomic technologies by adding platforms that will increase the scope of experiments that can be performed as well as providing automation and increased capacity to handle the increasing demand for these techniquesRead moreRead less
Functional genomics of light stress resistance in the model organism Chlamydomonas: combining molecular genetics, transcriptome and proteome analysis. This project aims at combining molecular genetics, transcriptome and proteome analysis to identify genes and pathways underlying high light stress tolerance in previously isolated mutants of the chlorophyte Chlamydomonas reinhardtii. Comprehensive profiles of transcriptome-proteome linkage will be constructed without the complications of multicel ....Functional genomics of light stress resistance in the model organism Chlamydomonas: combining molecular genetics, transcriptome and proteome analysis. This project aims at combining molecular genetics, transcriptome and proteome analysis to identify genes and pathways underlying high light stress tolerance in previously isolated mutants of the chlorophyte Chlamydomonas reinhardtii. Comprehensive profiles of transcriptome-proteome linkage will be constructed without the complications of multicellularity for this unicellular photosynthetic model organism. We will establish a public proteome reference database and provide new microarrays and molecular markers beneficial for research in Chlamydomonas. We expect to advance understanding of high light resistance mechanisms so that it will eventually be applicable to improve productivity in crop plants growing under various environmental stress conditions.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