A New Model For The Pathogenesis Of Rheumatic Fever: Superantigen Priming Of The Immune Response To Group A Streptococci
Funder
National Health and Medical Research Council
Funding Amount
$248,820.00
Summary
Acute rheumatic fever (ARF) is now rare in developed countries. However, it remains a major problem in Aboriginal Australians in the NT where the rate of ARF is the highest in the world. This leads to high rates of rheumatic heart disease (up to 3% of individuals in some communities) and a premature mortality of over four times that for developing countries. Immunisation and improved living conditions offer a long-term solution but these remain a distant prospect. In the short and medium term, c ....Acute rheumatic fever (ARF) is now rare in developed countries. However, it remains a major problem in Aboriginal Australians in the NT where the rate of ARF is the highest in the world. This leads to high rates of rheumatic heart disease (up to 3% of individuals in some communities) and a premature mortality of over four times that for developing countries. Immunisation and improved living conditions offer a long-term solution but these remain a distant prospect. In the short and medium term, control of this ARF will partly depend on new and better treatment and prevention strategies. To achieve these goals a deeper understanding of the immune mechanisms underlying this disease is urgently needed. It is known that ARF is caused by an abnormal immune response following streptococcal infection. This leads to the production of cells called T cells that attack the body s own tissues rather than the bacteria itself. This autoimmune disease is responsible for the heart damage that underlies ARF. It is believed that this proces only occurs when susceptible individuals are infected with specific rheumatogenic strains of streptococci. However there are a number of deficiencies in this model and it is proposed that there is an additional factor responsible for the abnormal immune response in ARF. This project will explore the possibility that bacterial toxins called superantigens are the critical missing factor , by studying the immune response in ARF. Superantigens are produced by certain streptococci and staphylococci, and are potent in minute quantities causing widespread activation of the immune system. They have been found to play an important role in a number of autoimmune diseases and the type of immune response found in ARF fits well with that expected if superantigens were involved. If superantigens play an important role in causing the abnormal immune response in ARF then a number of new avenues would open for the treatment and prevention of this disease.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100306
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Does spurious maternal-fetal signalling support the evolution of a placenta. This project aims to test a model that explains how the placenta has evolved as a new organ more than 100 times in fishes, reptiles, and mammals including our own ancestors. The project will assess whether regulatory components of the placenta evolve as a result of spurious maternal-fetal signalling following egg retention and eggshell loss in viviparous reptiles. Expected outcomes of this project include a new understa ....Does spurious maternal-fetal signalling support the evolution of a placenta. This project aims to test a model that explains how the placenta has evolved as a new organ more than 100 times in fishes, reptiles, and mammals including our own ancestors. The project will assess whether regulatory components of the placenta evolve as a result of spurious maternal-fetal signalling following egg retention and eggshell loss in viviparous reptiles. Expected outcomes of this project include a new understanding of how complex organs originate and evolve in animals. This will benefit society through a broader depth of understanding of our own evolutionary history and provides a framework for future studies to investigate the origin and evolution of organs more broadly in animals.Read moreRead less
The evolution of female resistance to male reproductive traits in animals. Australia has an outstanding international reputation in the fields of Ecology and Evolution. This study will reinforce Australia's excellence in these fields. Sexual conflict is a topic of great scientific interest because it has important implications for evolutionary theory and our understanding of the diverse strategies that animals use to attract or repel potential mates. Consequently, articles on this topic feature ....The evolution of female resistance to male reproductive traits in animals. Australia has an outstanding international reputation in the fields of Ecology and Evolution. This study will reinforce Australia's excellence in these fields. Sexual conflict is a topic of great scientific interest because it has important implications for evolutionary theory and our understanding of the diverse strategies that animals use to attract or repel potential mates. Consequently, articles on this topic feature regularly in top international scientific journals. In addition, research on the unique social behaviours of Australian animals holds general public interest and plays an important role in attracting young people to careers in science. Read moreRead less
Old genes learning new tricks: characterising regulatory changes driving increased heart complexity during vertebrate evolution. The heart has dramatically increased in morphological complexity during vertebrate evolution but the molecular basis driving these major changes remains unknown. Using comparative genomics approaches, this project will explore changes in the regulation of genes involved in heart formation that lead to changes in cardiac structure. It will elucidate for the first time t ....Old genes learning new tricks: characterising regulatory changes driving increased heart complexity during vertebrate evolution. The heart has dramatically increased in morphological complexity during vertebrate evolution but the molecular basis driving these major changes remains unknown. Using comparative genomics approaches, this project will explore changes in the regulation of genes involved in heart formation that lead to changes in cardiac structure. It will elucidate for the first time the cardiac regulatory repertoire in zebrafish and will compare it with that of fly and mouse using cutting-edge bioinformatics pipelines. This work will unravel cardiac-specific regulatory modifications that give rise to evolutionary changes. On a broader scale, it will shed new light on the role of regulatory innovations over gene innovations in the emergence of new traits.Read moreRead less
Linkages between productivity and consistent behavioural traits in fish: implications for harvesting, climate impacts, and selective breeding for aquaculture. The extent to which behavior, growth and reproduction are genetically linked in fish populations is unknown, but critical for predicting the impacts of fish harvesting and climate warming, and developing fish stains for aquaculture. If strongly linked, fish harvest will always remove aggressive, large and productive fish, requiring their p ....Linkages between productivity and consistent behavioural traits in fish: implications for harvesting, climate impacts, and selective breeding for aquaculture. The extent to which behavior, growth and reproduction are genetically linked in fish populations is unknown, but critical for predicting the impacts of fish harvesting and climate warming, and developing fish stains for aquaculture. If strongly linked, fish harvest will always remove aggressive, large and productive fish, requiring their protection; in aquaculture, selecting for productive fish will also increase aggression-related injuries. If not strongly linked, we may be able to select for high productivity and low aggression in fish, or high productivity and low metabolism, thus reducing feed costs in aquaculture associated with aggressive behaviour leading to injury and infection, and reduced growth at warmer temperatures.Read moreRead less
The role of natural selection in macroevolution: a case study examining convergence of form and function in marine predator guilds. Darwin's theory of evolution natural selection is one of the most successful in the history of science and provides the framework for modern biology: however, areas of debate or uncertainty are often misinterpreted by non-scientists as indication of fundamental flaws in the theory. New 'hi-tech' tools provide the opportunity to re-examine these areas, and also to de ....The role of natural selection in macroevolution: a case study examining convergence of form and function in marine predator guilds. Darwin's theory of evolution natural selection is one of the most successful in the history of science and provides the framework for modern biology: however, areas of debate or uncertainty are often misinterpreted by non-scientists as indication of fundamental flaws in the theory. New 'hi-tech' tools provide the opportunity to re-examine these areas, and also to demonstrate the process of science to the public. The new tool is Computational Biomechanics, the future of studying biological form, and this project will further develop the leading role of Australian research in this technology which has applications for palaeontology, environmental management, medical science, and the next generation of engineering using 'biomaterials'.Read moreRead less
Molecular dissection of the functional regions of genes that encode actinins (ACTN2 and ACTN3) and their contribution to normal variation in skeletal muscle function. The project has discovered a common genetic variant that affects skeletal muscle structure, function and metabolism and influences athletic ability, and response to diet and exercise. The project will study how this gene influences muscle bulk and strength, the metabolic efficiency of muscle and the risk of obesity in the general ....Molecular dissection of the functional regions of genes that encode actinins (ACTN2 and ACTN3) and their contribution to normal variation in skeletal muscle function. The project has discovered a common genetic variant that affects skeletal muscle structure, function and metabolism and influences athletic ability, and response to diet and exercise. The project will study how this gene influences muscle bulk and strength, the metabolic efficiency of muscle and the risk of obesity in the general population.Read moreRead less
Sedimentary processes on sandy coasts in southern Australia. This project aims to reconstruct sedimentary processes and evolution of key coastal plains in southern Australia. These low-lying coasts, and the settlements and infrastructure on them, are vulnerable to inundation and shoreline erosion. Past behaviour of different types of coasts will be determined by combining innovative geospatial techniques to map morphology and past changes, geophysical imaging of stratigraphy and geochronology. T ....Sedimentary processes on sandy coasts in southern Australia. This project aims to reconstruct sedimentary processes and evolution of key coastal plains in southern Australia. These low-lying coasts, and the settlements and infrastructure on them, are vulnerable to inundation and shoreline erosion. Past behaviour of different types of coasts will be determined by combining innovative geospatial techniques to map morphology and past changes, geophysical imaging of stratigraphy and geochronology. The outcome will be models that explain responses to sediment availability, past storm history and sea-level changes. This will benefit sustainable coastal planning and management, providing geomorphological evidence to support erosion hazard assessments of these and adjacent coasts.Read moreRead less
Mechanisms of antifungal resistance in blackleg disease of canola. This project aims to determine how fungicide resistance evolves in the fungus Leptosphaeria maculans, the major pathogen of the oilseed crop canola. Global food production has become more reliant on the use of antifungal agents to protect crops, however these advances are now threatened by the emergence of drug-resistant microbes. The knowledge generated by this project will be used to reduce the risk of resistance evolving in po ....Mechanisms of antifungal resistance in blackleg disease of canola. This project aims to determine how fungicide resistance evolves in the fungus Leptosphaeria maculans, the major pathogen of the oilseed crop canola. Global food production has become more reliant on the use of antifungal agents to protect crops, however these advances are now threatened by the emergence of drug-resistant microbes. The knowledge generated by this project will be used to reduce the risk of resistance evolving in populations of the blackleg fungus. This will have economic benefits through ensuring increased canola yields, while providing health and environmental benefits through minimisation of use of fungicides.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE140100023
Funder
Australian Research Council
Funding Amount
$360,000.00
Summary
Innovative isotopic techniques to study the response of soil and water resources to modern and past climate change. Innovative isotopic techniques to study the response of soil and water resources to modern and past climate change: The emergence of innovative isotopic tools has provided unprecedented opportunities to improve our understanding of the processes that shape the earth's resources and environment. The plasma-source mass spectrometer will be dedicated to applying these techniques to ea ....Innovative isotopic techniques to study the response of soil and water resources to modern and past climate change. Innovative isotopic techniques to study the response of soil and water resources to modern and past climate change: The emergence of innovative isotopic tools has provided unprecedented opportunities to improve our understanding of the processes that shape the earth's resources and environment. The plasma-source mass spectrometer will be dedicated to applying these techniques to earth surface processes, and establishing unique capabilities to decipher how soil and water resources respond to modern and past climate change in Australia.Read moreRead less