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
Muscle fibre excitability and calcium regulation in skeletal muscle of amphibians and mammals. The fundamental role of skeletal muscle is posture and movement. Essential for this is a specialised cell structure and a complex regulation of function. This project will define key aspects of muscle structure and functional regulation crucial to developing targets for improving function under stressed states such as fatigue, disease and age.
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
Regulating calcium handling in skeletal muscle - implications for muscle contraction, injury and repair, ageing and development. Understanding the mechanisms regulating calcium in skeletal muscle has important relevance for studying muscle growth and development, injury and repair, and for identifying therapeutic targets and potential therapies for ageing-related disorders, reconstructive surgery, sporting and workplace injuries, and muscle diseases. Combining cell physiology, fluorescence micro ....Regulating calcium handling in skeletal muscle - implications for muscle contraction, injury and repair, ageing and development. Understanding the mechanisms regulating calcium in skeletal muscle has important relevance for studying muscle growth and development, injury and repair, and for identifying therapeutic targets and potential therapies for ageing-related disorders, reconstructive surgery, sporting and workplace injuries, and muscle diseases. Combining cell physiology, fluorescence microscopy and digital imaging technologies for studying multicellular tissues such as skeletal muscle will enhance the international competitiveness of Australian biological research. The research will optimise development of gene delivery systems that may find eventual application for muscle wasting disorders and conditions where muscle weakness compromises quality of life.Read moreRead less
Calcium cycling and heat generation in skeletal muscle fibres. This project aims to uncover the mechanisms that enable mammalian skeletal muscle to play a major role in generating the heat required to maintain a constant body temperature. The ability to modulate body heat played a defining role in the evolution of species, their behaviour and global distribution. How heat production occurs in resting muscle is of fundamental importance and will be defined for the first time, providing new avenu ....Calcium cycling and heat generation in skeletal muscle fibres. This project aims to uncover the mechanisms that enable mammalian skeletal muscle to play a major role in generating the heat required to maintain a constant body temperature. The ability to modulate body heat played a defining role in the evolution of species, their behaviour and global distribution. How heat production occurs in resting muscle is of fundamental importance and will be defined for the first time, providing new avenues to manipulate metabolic rate and counter obesity.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
Novel manufacturing methods for tissue engineering scaffolds. Novel methods of manufacturing biodegradable polymer scaffolds around which new tissue can be grown within the human body will be developed. Surfactant - polymer assemblies will be used to produce highly porous scaffolds of tunable pore size and connectivity, shape and strength. The results will create a new avenue for systematic investigations into the effects of scaffold structure on tissue growth. This research will lead to the dev ....Novel manufacturing methods for tissue engineering scaffolds. Novel methods of manufacturing biodegradable polymer scaffolds around which new tissue can be grown within the human body will be developed. Surfactant - polymer assemblies will be used to produce highly porous scaffolds of tunable pore size and connectivity, shape and strength. The results will create a new avenue for systematic investigations into the effects of scaffold structure on tissue growth. This research will lead to the development of reliable, well-controlled manufacturing techniques for tissue engineering scaffolds, revolutionising current scaffold manufacturing practices. It will enhance existing collaborations between the University of Melbourne and the Bernard O'Brien Institute of Microsurgery.Read moreRead less
From single cell to collective cell migration in multicellular systems: mathematical and computational modelling of real biological systems. Cell motion is a complex process, fundamental to physiological processes. This project provides the necessary quantitative framework to understand the full range of cell migration patterns observed in vivo, thereby contributing tools for cancer treatment and tissue engineering, as well as enhancing Australia's reputation in mathematical biology.