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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
Membrane attack complex/perforin-like proteins in developmental and neurobiology. This project will aim to use the fruit fly as a model system to understand how members of the perforin-like superfamily, a family of proteins more usually associated with mammalian immunity, function in embryonic and neural development. These data will eventually provide central insight into human diseases such as cancer and autism spectrum disorder.
Mechanisms that control the inheritance of mitochondrial DNA mutations. How do humans and other organisms prevent the accumulation of dangerous mitochondrial genome (mtDNA) mutations across generations? This Project aims to uncover the cellular and molecular pathways that help prevent the inheritance of mtDNA mutations to offspring by employing cutting-edge genetic technologies that the laboratory has recently developed in the germline of an animal model system. This Project will generate new kn ....Mechanisms that control the inheritance of mitochondrial DNA mutations. How do humans and other organisms prevent the accumulation of dangerous mitochondrial genome (mtDNA) mutations across generations? This Project aims to uncover the cellular and molecular pathways that help prevent the inheritance of mtDNA mutations to offspring by employing cutting-edge genetic technologies that the laboratory has recently developed in the germline of an animal model system. This Project will generate new knowledge in the area of mitochondrial genetics and evolution. Expected outcomes include the development of new theories for mtDNA inheritance, which should provide significant benefits for agricultural breeding programs and the interpretation of mtDNA inheritance patterns in the human population.Read moreRead less
Mechanosensitive properties and modulation of N-methyl-D-aspartate (NMDA) receptors by lipid environment. This project will provide new information about the molecular determinants which influence NMDA receptor channel gating that will significantly advance our understanding of a link between NMDA receptor function and many neurodegenerative diseases as well as pain and learning and memory. The outcomes of this project may lead to the discovery of novel lipid-based biomaterials for application i ....Mechanosensitive properties and modulation of N-methyl-D-aspartate (NMDA) receptors by lipid environment. This project will provide new information about the molecular determinants which influence NMDA receptor channel gating that will significantly advance our understanding of a link between NMDA receptor function and many neurodegenerative diseases as well as pain and learning and memory. The outcomes of this project may lead to the discovery of novel lipid-based biomaterials for application in medicine and the drug industry. This research is highly significant in relation to human health. The biological and nutritional aspects of polyunsaturated lipids and dietary fish oils have long been recognized. Thus this project will provide further knowledge that could benefit the health of the nation with consequent reduced health care costs.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
Unlocking the secrets of metabolic variation in a highly diverse bacterium. This project aims to explore metabolic diversity of Klebsiella pneumoniae, a bacterium relevant to the agricultural, veterinary, medical and biotechnology industries. It is expected to reveal significant insights into the biology of this diverse organism via an innovative combination of DNA sequence analyses and metabolic modelling. Expected outcomes include 4500 novel metabolic models and a novel population metabolic fr ....Unlocking the secrets of metabolic variation in a highly diverse bacterium. This project aims to explore metabolic diversity of Klebsiella pneumoniae, a bacterium relevant to the agricultural, veterinary, medical and biotechnology industries. It is expected to reveal significant insights into the biology of this diverse organism via an innovative combination of DNA sequence analyses and metabolic modelling. Expected outcomes include 4500 novel metabolic models and a novel population metabolic framework. This should provide major benefits for understanding bacterial ecology and evolution, and for future studies seeking to optimise industrial processes or prevent disease. It will also directly contribute to building Australia’s capacity in computational biology- a key driver of biotechnology innovation.Read moreRead less
Using venoms to map critical and evolutionary conserved vulnerabilities. We have developed and applied new functional genomic approaches to study venom evolution. Using CRISPR screening, we find that unrelated venoms act on cells by exploiting the same vulnerabilities. By functionally mapping these vulnerabilities for all venom classes, we can begin to develop universal venom antidotes. Conversely, much of what we know about venom mechanisms comes from a small percentage of the biodiversity with ....Using venoms to map critical and evolutionary conserved vulnerabilities. We have developed and applied new functional genomic approaches to study venom evolution. Using CRISPR screening, we find that unrelated venoms act on cells by exploiting the same vulnerabilities. By functionally mapping these vulnerabilities for all venom classes, we can begin to develop universal venom antidotes. Conversely, much of what we know about venom mechanisms comes from a small percentage of the biodiversity within a venom, and we have developed genomic tools to study the venom “dark matter”. This work will lead to the full molecular characterisation of venom biodiversity, and new venom components will be useful for research or as novel medicines.Read moreRead less
Insulin transport into the central nervous system. This project aims to understand transportation of peripheral insulin into the central nervous system and how it maintains energy balance. Insulin is essential for normal physiological functioning in the periphery and central nervous system, but some circumstances, including high-fat diets, reduce insulin signalling in the brain. This project examines the mechanisms of insulin transport into the central nervous system, and may improve our underst ....Insulin transport into the central nervous system. This project aims to understand transportation of peripheral insulin into the central nervous system and how it maintains energy balance. Insulin is essential for normal physiological functioning in the periphery and central nervous system, but some circumstances, including high-fat diets, reduce insulin signalling in the brain. This project examines the mechanisms of insulin transport into the central nervous system, and may improve our understanding of blood brain barrier insulin transport and dysfunction.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
Evolutionary genetics of bovid genomes over 60,000 years. This project will provide data critical for understanding the genetic background of modern cattle and bison, and how humans have shaped factors such as milk yield, growth rates and muscle mass. It will also reveal genes and genomic regions that were favoured in the domestication process, including those potentially linked to genes of commercial interest for future research. This pioneering ancient DNA approach will also be applicable to a ....Evolutionary genetics of bovid genomes over 60,000 years. This project will provide data critical for understanding the genetic background of modern cattle and bison, and how humans have shaped factors such as milk yield, growth rates and muscle mass. It will also reveal genes and genomic regions that were favoured in the domestication process, including those potentially linked to genes of commercial interest for future research. This pioneering ancient DNA approach will also be applicable to a variety of other domestic crops and animals. The unique temporal analysis of microevolution will provide crucial data for genetic research, and groundproof our attempts to analyse the timing and nature of human evolutionary history, major domestication events and inform conservation management.Read moreRead less