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
Estimating The Burden Of Group A Streptococcal Diseases In Victoria
Funder
National Health and Medical Research Council
Funding Amount
$386,760.00
Summary
Despite the considerable advances in the diagnosis and treatment of group A streptococcal (GAS) diseases made during the last century, the impressive spectrum of infections caused by this organism continues to have a significant impact in developed countries. This spectrum includes diseases that are mild but common (e.g. sore throat, skin sores), rare but very severe (e.g. bloodstream infections, flesh-eating bacteria) and those that are more common in developing countries and the Aboriginal pop ....Despite the considerable advances in the diagnosis and treatment of group A streptococcal (GAS) diseases made during the last century, the impressive spectrum of infections caused by this organism continues to have a significant impact in developed countries. This spectrum includes diseases that are mild but common (e.g. sore throat, skin sores), rare but very severe (e.g. bloodstream infections, flesh-eating bacteria) and those that are more common in developing countries and the Aboriginal population (e.g. rheumatic fever, kidney disease). Streptococcal sore throat remains one of the most common childhood infections, and severe group A streptococcal diseases are thought to be increasing in incidence in Australia. Yet, there are no accurate data on the incidence and costs of these or other GAS diseases in non-Aboriginal Australians, or in most other populations around the world. It is becoming more urgent to collect this data as numerous vaccine candidates are entering human trials, new approaches to the treatment of sore throat are emerging, and new strategies to treat and control the spread of severe disease are being developed. We propose a comprehensive strategy to measure the incidence, prevalence and costs of each group of GAS diseases. We will follow a group of families for 12 months to detect cases of GAS sore throat and skin sores and measure the impact on the family. We will survey children in schools to estimate the prevalence of skin sores. We will check hospital records to calculate the number of cases of rheumatic fever and kidney disease. And we will maintain surveillance for severe diseases by checking hospital and laboratory records. We will also check to see if family members of people with severe disease have the GAS bacterium in their throats. We will then compile these data into a comprehensive estimate of the burden of disease in Victoria, and estimate the cost-effectiveness of different treatment and prevention strategies.Read moreRead less
About time; a new biology for the mineralocorticoid receptor . Temporal control of cell function aligns biological pathways with environmental cues and is critical for optimal heath in mammals. This project will shed light on how a hormone receptor, the MR, modulates time keeping of biological clock time in cells. We will bring together cutting edge genetic modals and bioinformatic approaches with a unique set of research models to define the interaction between the MR and the circadian clock a ....About time; a new biology for the mineralocorticoid receptor . Temporal control of cell function aligns biological pathways with environmental cues and is critical for optimal heath in mammals. This project will shed light on how a hormone receptor, the MR, modulates time keeping of biological clock time in cells. We will bring together cutting edge genetic modals and bioinformatic approaches with a unique set of research models to define the interaction between the MR and the circadian clock and its role in the normal biology of the heart. New data will significantly enhance our understanding of the biology of MR and cortisol for the circadian time keeping function in peripheral tissues, and gain a clearer understand how our heart cells adapt to environmental circadian disruptors such as shift work. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE160100015
Funder
Australian Research Council
Funding Amount
$500,000.00
Summary
An Ultra High Resolution Mass Spectrometry Facility for Lipidomics Research. An ultra-high-resolution mass spectrometry facility for lipidomics research:
This proposal aims to establish an ultra-high-resolution, accurate mass spectrometry facility in Australia for comprehensive lipidomics research. The platform would consist of a Thermo Scientific Orbitrap Fusion mass spectrometer interfaced with ultra-high-pressure high-performance liquid chromatography. This proposal will address a major need ....An Ultra High Resolution Mass Spectrometry Facility for Lipidomics Research. An ultra-high-resolution mass spectrometry facility for lipidomics research:
This proposal aims to establish an ultra-high-resolution, accurate mass spectrometry facility in Australia for comprehensive lipidomics research. The platform would consist of a Thermo Scientific Orbitrap Fusion mass spectrometer interfaced with ultra-high-pressure high-performance liquid chromatography. This proposal will address a major need for advanced mass spectrometry-based lipid analysis capabilities across mammalian, plant, parasite, and microalgae research disciplines, as well as enabling fundamental studies of lipid separation, chemistry and reactivity. The instrumentation would be applicable to a diverse range of projects including studies of the role of lipid metabolism in mammalian biochemistry and cell biology, plant biology and parasitology, and micro algae biofuel production.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE200100117
Funder
Australian Research Council
Funding Amount
$1,275,000.00
Summary
A platform consortium for integrated 'systems-omics' research. The proposal aims to establish a multi-institutional integrated ‘systems-omics’ platform across two of Victoria’s leading research universities, and associated research institutes. The platform will consist of two cutting edge ultra-high resolution mass spectrometers (i) a Thermo Scientific Orbitrap Fusion LUMOS for rapid and comprehensive metabolomic profiling and detailed structural characterization, located at La Trobe University ....A platform consortium for integrated 'systems-omics' research. The proposal aims to establish a multi-institutional integrated ‘systems-omics’ platform across two of Victoria’s leading research universities, and associated research institutes. The platform will consist of two cutting edge ultra-high resolution mass spectrometers (i) a Thermo Scientific Orbitrap Fusion LUMOS for rapid and comprehensive metabolomic profiling and detailed structural characterization, located at La Trobe University, and (ii) a Thermo Scientific Orbitrap Q Exactive HFX for high-throughput, deep and reproducible quantitative proteome analysis, located at the University of Melbourne.This platform will address applications across the agri-biosciences, medicinal agriculture and fundamental biomedical sciences sectors.Read moreRead less