Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this ....Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this study will be a catalogue of functionally active circRNAs. Over the past decades, the wealth of knowledge on the function of linear mRNAs has had a significant impact on medicine and agriculture. Similarly understanding how circRNAs regulate cellular activities may have an analogous impact on humans.Read moreRead less
Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behav ....Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behaviour of therapeutic stem cells introduced into the body.Read moreRead less
Identification and characterisation of caspase inhibitors. Organisms use a tightly controlled process of cell death (termed apoptosis) to remove dangerous and unwanted cells. Dysregulation of this process can contribute to diseases such as cancer and autoimmune disease. Caspases are protease effectors of apoptosis. Regulation of their activity is vital for effective control of cell survival and death. Using a functional screening system invented by the 1st CI, we aim to isolate and characterise ....Identification and characterisation of caspase inhibitors. Organisms use a tightly controlled process of cell death (termed apoptosis) to remove dangerous and unwanted cells. Dysregulation of this process can contribute to diseases such as cancer and autoimmune disease. Caspases are protease effectors of apoptosis. Regulation of their activity is vital for effective control of cell survival and death. Using a functional screening system invented by the 1st CI, we aim to isolate and characterise novel inhibitors of caspases. Such inhibitors may in time be used as targets for development of therapeutic or diagnostic reagents aimed at manipulating the apoptotic process to diagnose, prevent or treat disease.Read moreRead less
How does Fat cadherin control organ size in Drosophila, and cancer in humans? The primary function of Fat cadherin is to dictate the appropriate size of organs in developing animals. Deficiency in the fat gene results in vastly overgrown organs and can lead to the formation of cancer in humans. Our study will provide important insights into how the size of organs are controlled during development. Our research findings will have important implications for several aspects of human health and biol ....How does Fat cadherin control organ size in Drosophila, and cancer in humans? The primary function of Fat cadherin is to dictate the appropriate size of organs in developing animals. Deficiency in the fat gene results in vastly overgrown organs and can lead to the formation of cancer in humans. Our study will provide important insights into how the size of organs are controlled during development. Our research findings will have important implications for several aspects of human health and biology, and will increase our understanding of diseases that arise due to aberrant tissue growth, such as cancer. Our research findings will thus be of substantial national benefit, given that cancer is now the biggest cause of death in Australia, and that more than 88,000 Australians are diagnosed with cancer each year. Read moreRead less
The development and evolution of the pelvic girdle in basal gnathostomes. Comparing the development of muscles, cartilage and bone in representatives of all three major groups of fish will provide information as to how structures evolved but also how the adult morphology is distributed in phylogeny. Because so little is known about the genetic mechanisms underlying the formation of the pelvic girdle in fish, it is important to start studying a model animal such as the zebrafish. The pathways unc ....The development and evolution of the pelvic girdle in basal gnathostomes. Comparing the development of muscles, cartilage and bone in representatives of all three major groups of fish will provide information as to how structures evolved but also how the adult morphology is distributed in phylogeny. Because so little is known about the genetic mechanisms underlying the formation of the pelvic girdle in fish, it is important to start studying a model animal such as the zebrafish. The pathways uncovered have the potential to describe mechanisms common to all jawed vertebrates, not only common to fish. Understanding the mechanisms that generate major morphological transition in the vertebrate lineage necessarily informs us about our own evolutionRead moreRead less
Socs proteins in development and disease. Socs proteins are a component of a pathway that is central to a range of developmental processes, including embryonic development. In addition, there is evidence that these proteins are perturbed in several disorders. This Project will enhance our understanding of the Socs proteins and their role in disease, and ultimately provide an opportunity to identify new therapeutic strategies.
Endocardial sprouting and mechano-signalling in heart trabeculation. This project aims to understand how the ventricles, the pumping chambers of the mammalian heart, form during embryonic life. Critical is the elaboration of trabeculae, myocardial projections that form a sponge-like layer on the inner surface of the chamber wall and which play vital roles in contraction, oxygen and nutrient exchange, conduction and septation. The project expects to develop a deeper understanding of trabeculation ....Endocardial sprouting and mechano-signalling in heart trabeculation. This project aims to understand how the ventricles, the pumping chambers of the mammalian heart, form during embryonic life. Critical is the elaboration of trabeculae, myocardial projections that form a sponge-like layer on the inner surface of the chamber wall and which play vital roles in contraction, oxygen and nutrient exchange, conduction and septation. The project expects to develop a deeper understanding of trabeculation using high resolution, single cell methodologies, and to investigate how bio-mechanical forces from contraction or blood flow influence chambers formation.Read moreRead less
Transcriptional regulation of erythropoiesis. The major expected outcome from this proposal will be development of a pipeline for the study of how transcription factors work at a genome level. There will be national benefit in the areas of Frontier Technologies, and Promoting and Maintaining Good Health. There will be specific outcomes with respect to development of tests for human blood diseases, future design of drugs to target the aberrant activities of transcription factors in genetic and de ....Transcriptional regulation of erythropoiesis. The major expected outcome from this proposal will be development of a pipeline for the study of how transcription factors work at a genome level. There will be national benefit in the areas of Frontier Technologies, and Promoting and Maintaining Good Health. There will be specific outcomes with respect to development of tests for human blood diseases, future design of drugs to target the aberrant activities of transcription factors in genetic and degenerative diseases. Also, a strong bridge will be built upon the previous collaborations of the research teams in Brisbane and Pennsylvania, which will facilitate advanced teaching and training of Australian PhD and post-doctoral scientists.Read moreRead less
Synthetic Molybdenum Enzymes. This project aims to produce synthetic molybdenum (Mo) enzymes, small molecules that share structural and functional attributes with the crucially important molybdopterin?Mo enzymes. These ubiquitous enzymes are essential for plant and animal health, natural cycles involving carbon, nitrogen and sulfur, and global climate control and atmospheric albedo (reflectance); consequently, they impact heavily on commerce, the environment and society. The study will provid ....Synthetic Molybdenum Enzymes. This project aims to produce synthetic molybdenum (Mo) enzymes, small molecules that share structural and functional attributes with the crucially important molybdopterin?Mo enzymes. These ubiquitous enzymes are essential for plant and animal health, natural cycles involving carbon, nitrogen and sulfur, and global climate control and atmospheric albedo (reflectance); consequently, they impact heavily on commerce, the environment and society. The study will provide urgently needed insights into the fundamental Mo?sulfur chemistry of the enzyme active sites and inform efforts to reduce the negative impacts of enzyme dysfunction and the design of new commercial catalysts.Read moreRead less
Bioinorganic Chemistry of Molybdenum. Enzymes containing the trace element molybdenum play crucial roles in plant, animal and human health, drug metabolism, environmental processes and climate. This international, multidisciplinary project will advance our understanding of the structure and function of these enzymes at the atomic level and inform strategies to reduce the impact of crop, livestock and human diseases and adverse environmental (e.g. algal blooms, leaching of toxic arsenic) and clim ....Bioinorganic Chemistry of Molybdenum. Enzymes containing the trace element molybdenum play crucial roles in plant, animal and human health, drug metabolism, environmental processes and climate. This international, multidisciplinary project will advance our understanding of the structure and function of these enzymes at the atomic level and inform strategies to reduce the impact of crop, livestock and human diseases and adverse environmental (e.g. algal blooms, leaching of toxic arsenic) and climatic events. Effective strategies would be of enormous social and economic benefit to Australia. The training of skilled scientists and access to major overseas facilities are additional benefits of the project.Read moreRead less