Though vaccination has had a major impact on the number of persons becoming infected, chronic infection with the hepatitis B virus (HBV) still remains a major worldwide problem, with 350 million people chronically infected. The existence of HBV vaccine escape mutants and the fact that 5% of vaccinees fail to respond implies that HBV will remain a significant public health problem for the foreseeable future. Current treatments for chronic HBV infection have a low success rate (~20%) and patients ....Though vaccination has had a major impact on the number of persons becoming infected, chronic infection with the hepatitis B virus (HBV) still remains a major worldwide problem, with 350 million people chronically infected. The existence of HBV vaccine escape mutants and the fact that 5% of vaccinees fail to respond implies that HBV will remain a significant public health problem for the foreseeable future. Current treatments for chronic HBV infection have a low success rate (~20%) and patients with chronic infection are expected to die prematurely due to chronic liver disease or primary liver cancer. Interestingly, exposure to HBV can lead to either acute resolving or chronic HBV infection. Like chronic infections, acute infections involve spread of virus to virtually every hepatocyte, followed by rapid clearance of the virus mediated by the host immune response. Our immediate aim is to study the resolution of acute HBV infections to determine how the stable intracellular viral genome, covalently closed circular DNA (cccDNA), is cleared from the nucleus of infected hepatocytes. Our broad long-term aim is to develop new and effective treatments for chronic HBV infection based on a better understanding of how acute HBV infections are resolved by the host. Based on our previous work we believe that clearance of cccDNA requires hepatocyte death, together with compensatory proliferation of other infected hepatocytes. We will perform detailed studies in duck hepatitis B virus (DHBV) infected ducks to determine if hepatocyte death and compensatory proliferation are essential to clear the infection, or if mechanisms exist for clearance that do not involve cell destruction.Read moreRead less
Gene Based Treatment Strategies For Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$2,630,000.00
Summary
Diabetic retinopathy is the leading cause of blindness in the working population of developed countries and it is an increasing problem in the developing world. Present therapy involves extensive laser destruction of the light-detecting part of he retina. In addition, it is not only effective when administered at an appropriate stage in the disease process. Consequently, there is an urgent need for the development of better, prophylactic, easily administrable and cheaper therapies. This project ....Diabetic retinopathy is the leading cause of blindness in the working population of developed countries and it is an increasing problem in the developing world. Present therapy involves extensive laser destruction of the light-detecting part of he retina. In addition, it is not only effective when administered at an appropriate stage in the disease process. Consequently, there is an urgent need for the development of better, prophylactic, easily administrable and cheaper therapies. This project aims to develop a potentially permanent solution to alleviate diabetes-related blindness in the world. The project combines several very recent scientific advances into one strategy to combat diabetic retinopathy at a molecular level. Vision is our most important sensory organ that cannot be replaced. Thus, human trials can only be conducted following extensive animal safety and efficacy trials. To date the development of new therapies has been seriously hampered by the lack of appropriate, easy to reproduce animal models for different stages of diabetic retinopathy. In addition, it aims to identify new therapeutic agents from molecules that are naturally produced by the retina while fighting the disease. Finally, tested and evaluated in the animal models. The most successful therapeutic candidates will then be further developed for human trials.If successful, our approach will potentially have a major impact on the treatment of diabetic retinopathy and possibly on all diabetic vascular diseases. A single injection might only be necessary to prevent the development of diabetic retinopathy, which would represent a significant weapon in the management of patients. In addition, successful application of secretion gene therapy in the eye might open up the possibility to introduce the same concept for the treatment of larger organs undergoing microvascular changes as a result of diabetes.Read moreRead less
Development Of A Novel Biosensor Using Magnetically Amplified Luminescence For The Early Detection Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$267,500.00
Summary
Cancer is often not detected until it has invaded surrounding tissues and spread to other organs. Current treatment is then often ineffective, and prognosis poor. Early detection of cancer is therefore essential for improved disease management. Such methods must be cheap, non-invasive, and rapid with high sensitivity and specificity. We are investigating a new biosensor technology that satisfies these criteria. This method uses magnetically amplified luminescence for the detection of low levels ....Cancer is often not detected until it has invaded surrounding tissues and spread to other organs. Current treatment is then often ineffective, and prognosis poor. Early detection of cancer is therefore essential for improved disease management. Such methods must be cheap, non-invasive, and rapid with high sensitivity and specificity. We are investigating a new biosensor technology that satisfies these criteria. This method uses magnetically amplified luminescence for the detection of low levels of cancer cells in clinical samples (urine, faeces, blood, biopsy), using telomerase as a marker.Read moreRead less
Impact and Effectiveness of Personal Ventilation in Open Plan Offices: a study of the Task Air system. Centralised air-conditioning systems are the standard for commercial office buildings in Australia. These systems are energy intensive, typically accounting for around 50% of building energy use. However, lack of occupant control over set temperatures or air movement tends to reduce thermal comfort, which can adversely affect worker productivity. The benefit of this project is that it will qu ....Impact and Effectiveness of Personal Ventilation in Open Plan Offices: a study of the Task Air system. Centralised air-conditioning systems are the standard for commercial office buildings in Australia. These systems are energy intensive, typically accounting for around 50% of building energy use. However, lack of occupant control over set temperatures or air movement tends to reduce thermal comfort, which can adversely affect worker productivity. The benefit of this project is that it will quantify the improvements to occupant comfort and energy savings possible with a PV system. This study will enable PV systems to be evaluated as an alternative to traditional air-conditioning, thereby demonstrating their effectiveness as a means of improving the sustainability rating of commercial office buildings in Australia.Read moreRead less
The Characterisation of Fires in Tunnels. A series of 22 fires ranging from 2 megawatt up to 20 megawatt intensity will be set under controlled conditions in unused tunnel facilities, in New South Wales. Instrumentation in the tunnel, donated by the State Rail Authority of New South Wales, will monitor the movement of particulates (smoke). This information is vital to tunnel design, and for passenger life safety. This information will be applicable to all tunnels worldwide.
Understanding How Sepsis Causes Kidney Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$471,770.00
Summary
Acute renal failure is a serious condition that affects up to 20% of patients in Intensive Care Units. Sepsis and septic shock remain the most important causes of acute renal failure in critically ill patients. Despite our ability to support vital organs and resuscitate patients, the incidence and mortality of septic acute renal failure remain unacceptably high at up to 55%. There have been no major advances in our understanding of its pathogenesis and in its prevention or treatment over the las ....Acute renal failure is a serious condition that affects up to 20% of patients in Intensive Care Units. Sepsis and septic shock remain the most important causes of acute renal failure in critically ill patients. Despite our ability to support vital organs and resuscitate patients, the incidence and mortality of septic acute renal failure remain unacceptably high at up to 55%. There have been no major advances in our understanding of its pathogenesis and in its prevention or treatment over the last 50 years. The traditional view is that sepsis-induced renal failure results from reduced perfusion of the kidney secondary to the low blood pressure. In a model of sepsis in sheep with renal failure, we demonstrated, however, that renal blood vessels dilated and blood flow increased. Furthermore, renal function improved following treatment with vasoconstrictor drugs that raised blood pressure and renal blood flow. These findings indicate that renal ischaemia is not the cause of the renal dysfunction in sepsis. We hypothesise that sepsis causes renal vasodilatation, which reduces glomerular filtration rate and renal function, and induces a delayed development of apopotosis. We will study in sepsis 1) the effects of a treatment to increase glomerular filtration rate 2) the development of apoptosis and the effect of an anti-apoptotic drug, and 3) whether there is bioenergetic failure in the kidney in sepsis and the effects of treatments on this. Finally, in septic patients we will measure renal blood flow and determine the effects of our novel treatment on this and renal function. These studies will significantly increase our understanding of the factors causing acute renal failure in sepsis. They are likely to lead to the development of new therapies to improve renal function in sepsis and their effectiveness will be examined in septic animals and patients.Read moreRead less
Consumer Information Materials And A Communication Aid For Diagnostic Tests For Breast Disease
Funder
National Health and Medical Research Council
Funding Amount
$105,863.00
Summary
Many studies have now shown that the majority of patients want to participate in clinical decisions about medical treatments they might receive. As a result, information materials are being developed to help consumers and doctors work together to reach satisfying treatment decisions which are based on the best available evidence and also reflect the individual patient's needs and preferences about the treatment options. Very little is known, however, about whether consumers also want to particip ....Many studies have now shown that the majority of patients want to participate in clinical decisions about medical treatments they might receive. As a result, information materials are being developed to help consumers and doctors work together to reach satisfying treatment decisions which are based on the best available evidence and also reflect the individual patient's needs and preferences about the treatment options. Very little is known, however, about whether consumers also want to participate in decisions about whether to have a medical test. Tests can be trivial, such as a blood or urine test, or quite major and invasive, such as a biopsy or a colonoscopy. People considering a medical test might want to know the answers to the following questions: What is my chance of having the disease being tested for? If the test result is positive what is the chance I have the disease? If the test result is negative what is the chance I have the disease anyway? How will the test result influence treatment of my condition? What are possible side-effects of the test? Generally information materials about medical tests only describe the test itself, and do not contain the information people need to answer these questions. Even doctors may not have to hand the data needed to answer these questions. Yet without this information, consumers cannot make truly informed and rational choices about whether to have the test. This project aims to find out whether consumers want to participate in decisions about medical tests, what information they would want to do this, and to develop and trial information materials and a communication aid for a small number of breast cancer tests. We will use tests for diagnosing breast cancer as our model but we anticipate the work will be applicable across a wide range of medical tests.Read moreRead less
Loop-mediated Isothermal Amplification(LAMP): A Novel Tool For The Diagnosis Of Mixed Malaria Infections In Elimination Settings
Funder
National Health and Medical Research Council
Funding Amount
$101,877.00
Summary
The malaria elimination agenda will require the development of novel, field applicable diagnostic tools to detect asymptomatic carriers of P.falciparum and non-falciparum malaria infections. Loop-mediated isothermal amplification (LAMP) has been demonstrated to be a novel, sensitive, specific nucleic acid amplification technique. My project aims to optimise LAMP into a high-throughput field applicable molecular diagnostic tool capable of diagnosing malaria in elimination settings
Development of a Compartment Fire Behaviour Training (CFBT) Database. In recent years, incidents of fire flashover have caused considerable destruction to property and the loss of life. Fire prediction and understanding is an area of significance to both the Australian public and the firefighting profession. The NSW Fire Brigade has recently introduced Compartment Fire Behaviour Training (CFBT). To extend this scheme, a database of configurations will be developed using computational modelling, ....Development of a Compartment Fire Behaviour Training (CFBT) Database. In recent years, incidents of fire flashover have caused considerable destruction to property and the loss of life. Fire prediction and understanding is an area of significance to both the Australian public and the firefighting profession. The NSW Fire Brigade has recently introduced Compartment Fire Behaviour Training (CFBT). To extend this scheme, a database of configurations will be developed using computational modelling, allowing firefighters the ability to experience virtually different situations. Detailed experimental studies will be conducted to validate the numerical model. This database will have use and significance beyond Australia and successful implementation promises reductions in the loss of life and property.Read moreRead less
Vibration Isolation Technology and Instrumentaion for Geophysical Surveys. Many geophysical exploration instruments are limited in sensitivity by vibration induced noise. New techniques of vibration isolation have been shown to eliminate vibration induced noise in a vibrating wire magnetic gradiometer. This project will create fully integrated sensor ?isolation packages for airborne and underwater applications, both for gradiometers and for ground penetrating radars. The project will signific ....Vibration Isolation Technology and Instrumentaion for Geophysical Surveys. Many geophysical exploration instruments are limited in sensitivity by vibration induced noise. New techniques of vibration isolation have been shown to eliminate vibration induced noise in a vibrating wire magnetic gradiometer. This project will create fully integrated sensor ?isolation packages for airborne and underwater applications, both for gradiometers and for ground penetrating radars. The project will significantly benefit the mineral exploration industry as well as underwater detection of cables and ship wrecks.Read moreRead less