Using Nanotechnology To Improve The Therapeutic Efficacy Of Iron Chelators
Funder
National Health and Medical Research Council
Funding Amount
$692,769.00
Summary
Iron loading disorders (such as thalassaemia) represent an important class of human disease. As part of the treatment for these diseases, the iron needs to be removed and this is often done using iron-binding drugs known as iron chelators. Current chelators are not ideal due to side effects or onerous delivery methods. The goal of this project is to use nanotechnology to develop more effective ways of delivering chelators to improve their effectiveness and reduce toxicity.
One of the current challenges in public health is to translate the progress from the Human Genome Project into reduced morbidity and mortality from disease. Once genetic defects are characterised, knowledge about the variability in severity of disease in mutation carriers, is important from a public health perspective. Hereditary Haemochromatosis (HH) is a common genetic disorder of iron overload that results in a wide spectrum of disease, varying from non-specific symptoms to severe damage to l ....One of the current challenges in public health is to translate the progress from the Human Genome Project into reduced morbidity and mortality from disease. Once genetic defects are characterised, knowledge about the variability in severity of disease in mutation carriers, is important from a public health perspective. Hereditary Haemochromatosis (HH) is a common genetic disorder of iron overload that results in a wide spectrum of disease, varying from non-specific symptoms to severe damage to liver, heart, pancreas and joints from iron deposition. It is easily treatable by regular blood donation, and population-based screening for HH has therefore been advocated. In this study we aim to address gaps in the existing data on HH regarding dietary and lifestyle factors that contribute to the variable clinical picture of HH. The study will be based on the Melbourne Collaborative Cohort Study, a cohort of 31,500 men and women who have been followed for approximately 10 years. Information on dietary and lifestyle factors was collected at initial enrollment, along with a blood specimen. We will test all non-Southern European participants (31,176) for the common HH mutations in the HFE gene and then select a subgroup of 1150 people, including all people with the main genetic defect as well as a comparison group, for further clinical followup. Participants will have genetic counselling and informed consent will be obtained. Participants will complete a short questionnaire and give a blood sample for measurement of iron overload, liver function, and other relevant blood tests, then undergo a brief clinical examination. Results of all tests will be given at a followup visit by genetic counsellor or physician. This study will provide important data on natural history of HH risk factors that influence variability in clinical presentation and the association of HFE mutations with chronic diseases and all cause mortality.Read moreRead less
Effects Of Testosterone And Oestrogen On Body Composition
Funder
National Health and Medical Research Council
Funding Amount
$348,768.00
Summary
Masculinising and feminising hormones such as testosterone and oestrogen respectively are important hormones controlling the amount of muscle, fat and bone in the body. By studying people with conditions such as prostate cancer where these hormone levels are disrupted, we aim to understand how testosterone and oestrogen affects various body systems, which may lead to new treatments for important public health problems of frailty, obesity and heart disease, and osteoporosis.
Understanding and modifying vortex structures in wind turbine wakes. At a fundamental research level, Australia's active participation in this area of national priority and research strength will be advanced through our published research, which will increase our understanding of wind turbine wakes and their effects in wind farms. This understanding will then be used to produce improved methods of predicting wind turbine performance. Such methods are needed by wind energy designers to produce b ....Understanding and modifying vortex structures in wind turbine wakes. At a fundamental research level, Australia's active participation in this area of national priority and research strength will be advanced through our published research, which will increase our understanding of wind turbine wakes and their effects in wind farms. This understanding will then be used to produce improved methods of predicting wind turbine performance. Such methods are needed by wind energy designers to produce better wind farms. It will also be used to recommend how to improve the aerodynamic design of turbine components, such as the blades and hub. Numerical tools will be developed for industry use, and training will be provided to personnel, thereby increasing the capabilities of Australia's growing wind energy industry.Read moreRead less
Reducing rocket resonance is the key to safer spaceflight. This fellowship considers a particularly dangerous component of rocket launch, which is the potential for destructive feedback loops to form either in the nozzle, or between the nozzle and the launch pad. CI Edgington-Mitchell is a world leader in the study of resonance in jet engines, having developed best-in-field methodologies for the problem. In this innovative fellowship, he will apply these methodologies to better understand the da ....Reducing rocket resonance is the key to safer spaceflight. This fellowship considers a particularly dangerous component of rocket launch, which is the potential for destructive feedback loops to form either in the nozzle, or between the nozzle and the launch pad. CI Edgington-Mitchell is a world leader in the study of resonance in jet engines, having developed best-in-field methodologies for the problem. In this innovative fellowship, he will apply these methodologies to better understand the dangerous resonances that can occur during rocket launch, using a combination of experimental, numerical, and theoretical techniques, in partnership with NASA, Stanford, and the CNRS.Read moreRead less
Does Early Overnutrition Differentially Alter Hypothalamic Neuropeptides That Regulate Food Intake In The Rat
Funder
National Health and Medical Research Council
Funding Amount
$346,250.00
Summary
In Australia the incidence of obesity, in particular childhood obesity, is increasing dramatically, and the possible long term consequences of this are of great concern. The brain regulates appetite through a number of chemical transmitters such as neuropeptide Y (NPY) which is present in the brains of mammals and causes increased food intake. The effects of overeating from a young age on these brain transmitters has been largely ignored although this may impact on subsequent eating behaviour. I ....In Australia the incidence of obesity, in particular childhood obesity, is increasing dramatically, and the possible long term consequences of this are of great concern. The brain regulates appetite through a number of chemical transmitters such as neuropeptide Y (NPY) which is present in the brains of mammals and causes increased food intake. The effects of overeating from a young age on these brain transmitters has been largely ignored although this may impact on subsequent eating behaviour. In addition to NPY we will study other transmitters in the brain that have profound effects on appetite, some increasing, and others decreasing, food intake. These may form useful therapeutic targets for new drugs for obesity. Key targets we will study include melanocortins, glucagon-like peptide 1, urocortin, melanin concentrating hormone, agouti related peptide, and NPY. We will determine whether overnutrition from birth to weaning leads to changes in these appetite regulating neurotransmitters in the brain, and monitor the hormonal signals that impact on their activity. We will also determine whether early overnutrition exacerbates the subsequent responses to a high fat diet by comparison with rats made obese as adults. We will measure brain concentrations of the neurotransmitters, the amount released from the brain, and determine whether the feeding responses to injections of these agents is altered in obese animals. We have evidence that these transmitters interact in a co-ordinated fashion to affect feeding; this project will examine whether these interactions are maintained in the various types of obesity. Rats are commonly used for this type of study as the processes regulating feeding are very similar to those in humans and these agents cause similar effects in rats and humans. It is hoped that this information will provide new insight into the way brain adapts to overnutrition, and provide potential treatments for obesity and other feeding disorders.Read moreRead less
Investigation into flow over complex topography and escarpments for wind turbine siting using experimental and computational methods. This project will improve national capability to optimise power production from wind turbine farms in complex terrain by improving the understanding of the flow regime. By better understanding separated regions and the turbulent structures within these regions power production can be optimised and fatigue risks associated with turbine positioning in complex sites ....Investigation into flow over complex topography and escarpments for wind turbine siting using experimental and computational methods. This project will improve national capability to optimise power production from wind turbine farms in complex terrain by improving the understanding of the flow regime. By better understanding separated regions and the turbulent structures within these regions power production can be optimised and fatigue risks associated with turbine positioning in complex sites can be reduced. This will improve confidence in wind farm site assessment techniques and consequently reduce economic risks associated with current wind farm viability assessments. By increasing national capacity to generate clean energy stationary energy emissions can be reduced. This project will also deliver high calibre graduates that will be potential future industry leaders.Read moreRead less
Optimizing blood flow in stented arteries: a fluid mechanics approach incorporating optical coherence tomography. Constriction in coronary arterial blood flow is a leading cause of death in Australia. Insertion of stents can rectify this problem but potentially lead to further complications. This project will use medical imaging data to construct computer models to study blood flow and particle motions in coronary arteries and improve stent designs.
Optimising haemodynamics in complex stented arteries. This project aims to optimise the hemodynamics (blood flow) in coronary arteries with high curvatures and bifurcations. Experience has shown that the build-up of plaque — and the resulting occlusion of blood flow — tends to occur in these complex arterial regions. The most common therapeutic strategy is the insertion of a stent to prop open the artery. However, the nature of the geometry often leads to post-stenting complications such as rest ....Optimising haemodynamics in complex stented arteries. This project aims to optimise the hemodynamics (blood flow) in coronary arteries with high curvatures and bifurcations. Experience has shown that the build-up of plaque — and the resulting occlusion of blood flow — tends to occur in these complex arterial regions. The most common therapeutic strategy is the insertion of a stent to prop open the artery. However, the nature of the geometry often leads to post-stenting complications such as restenosis and thrombosis, ultimately resulting in negative outcomes. In this project, advanced research methods from fluid dynamics and optimisation and control will be used to potentially minimise these highly undesirable effects.Read moreRead less
Horizontal convection at ocean-relevant proportions. This project aims to determine the role of buoyancy differences from solar radiation and vertical confinement. Flows created by lateral variation in heat or buoyancy are poorly understood when the horizontal length greatly exceeds the height, precisely the conditions relevant to industry and understanding the role of horizontal convection in Earth's oceans and in turn the delicate current system that maintains Earth's temperate climate. This p ....Horizontal convection at ocean-relevant proportions. This project aims to determine the role of buoyancy differences from solar radiation and vertical confinement. Flows created by lateral variation in heat or buoyancy are poorly understood when the horizontal length greatly exceeds the height, precisely the conditions relevant to industry and understanding the role of horizontal convection in Earth's oceans and in turn the delicate current system that maintains Earth's temperate climate. This project proposes computational and experimental efforts to probe the ultimate regime of heat transport in very shallow horizontal convection, benefiting humankind through improvements to future ocean and climate modelling efforts.Read moreRead less