Cytokine And Macrophage Determinants Of Pulmonary Inflammation During Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$455,899.00
Summary
Tuberculosis (TB) infects 33% of the world, causing over 2 million deaths per year. TB disease causes damaging lung pathology and new therapies to treat the infection and moderate inflammation are urgently required. TNF is essential for immunity to TB, acting to modulate inflammation. This grant will determine how soluble and membrane- bound TNF regulate the cellular and cytokine control of TB pathology and may lead to new therapies to limit inflammation in TB and other inflammatory diseases.
Establishing Guidelines for Coronial Best Practice Use of Internal Autopsy. Last year in Queensland 2700 Coronial internal autopsies were conducted at a cost of $5.3 million. In addition to the economic cost, other relevant concerns include few qualified personnel, public health risks, and cultural and religious sensitivities associated with internal autopsy. Anecdotal evidence suggests that for a number of these deaths, the internal autopsy was not necessary to establish cause or circumstance ....Establishing Guidelines for Coronial Best Practice Use of Internal Autopsy. Last year in Queensland 2700 Coronial internal autopsies were conducted at a cost of $5.3 million. In addition to the economic cost, other relevant concerns include few qualified personnel, public health risks, and cultural and religious sensitivities associated with internal autopsy. Anecdotal evidence suggests that for a number of these deaths, the internal autopsy was not necessary to establish cause or circumstance of death. The purpose of this research is to create guidelines to enable coroners to weight all sources of evidence before ordering internal autopsies The purpose is to decrease the number (and associated costs, risks and distress to families) of unnecessary internal autopsies being performed without compromising the finding as to cause and circumstance of death.Read moreRead less
Molecular approaches to solving current and emerging problems in the epidemiology and diagnosis of Marek's disease in Australia. Marek's disease (MD) is a ubiquitous viral disease of chickens that is currently controlled in meat chickens by blanket vaccination of all chickens. However, as has happened overseas, the efficacy of the HVT vaccine being used in Australia is breaking down resulting in subclinical and clinical losses due to MD. To assist industry deal with this situation we propose to ....Molecular approaches to solving current and emerging problems in the epidemiology and diagnosis of Marek's disease in Australia. Marek's disease (MD) is a ubiquitous viral disease of chickens that is currently controlled in meat chickens by blanket vaccination of all chickens. However, as has happened overseas, the efficacy of the HVT vaccine being used in Australia is breaking down resulting in subclinical and clinical losses due to MD. To assist industry deal with this situation we propose to develop novel molecular methods for the quantification of Marek's disease viruses (MDV) in the host and the environment, to use these methods to design effective early monitoring systems for MD in broilers that predict disease and performance outcomes, and to develop an epidemiological model that will predict the spread and severity of MD as failure of vaccinal protection progresses.Read moreRead less
Predictive And Prognostic Factors From The Tumour Microenvironment In Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$68,378.00
Summary
While most of the current treatments available are directed against cancerous tumour cells, there is increasing evidence that other factors within the tumour mass (or tumour microenvironment) may have an impact on prognosis. These factors include the lack of tissue oxygen and the immune response mounted by the body against the tumour cells. The impact of these factors on prognosis and their association with microRNAs (small RNA fragments which control protein production) will be investigated.
The routes of infection with sheep scrapie and agents that cause related prion diseases. We will define the routes by which the infective agents for scrapie, a debilitating disease of sheep, reach the nervous system after being consumed with food. Scrapie is from the same disease group (prion diseases) as mad cow disease. There would be a large economic cost were prion diseases to infect agricultural animals in Australia, through bioterrorism or accident. An outbreak in sheep could ruin the indu ....The routes of infection with sheep scrapie and agents that cause related prion diseases. We will define the routes by which the infective agents for scrapie, a debilitating disease of sheep, reach the nervous system after being consumed with food. Scrapie is from the same disease group (prion diseases) as mad cow disease. There would be a large economic cost were prion diseases to infect agricultural animals in Australia, through bioterrorism or accident. An outbreak in sheep could ruin the industry, as our export markets would be immediately blocked, and thousands of animals would be killed to stop disease spread. The benefit of clearly understanding how the infective agents reach the nervous system is that this may lead to strategies to intervene, and thus limit the spread and seriousness of infection.Read moreRead less
Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stick ....Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stickiness of malaria parasites to blood vessels. Our project will tackle the conditions of MP production and define new drugs to prevent it. It also will explain how the brain becomes affected by high numbers of MP. Our results will cast new light on why the brain functions abnormally when its blood vessels become modified.Read moreRead less
Cell Migration And Granuloma Formation In The Expression Of Protective Immunity Against Tuberculosis In The Lung
Funder
National Health and Medical Research Council
Funding Amount
$212,036.00
Summary
Tuberculosis (TB) remains an enormous problem worldwide and a continuing health problem in Australia. Most TB is not due to disease at the time of infection, but is a reactivation of dormant infection in people who have never eradicated the organisms. This study will investigate, in mice, how TB is initially contained within the lungs and how reactivation occurs. All mice infected with TB control the infection initially. T lymphocytes are activated and T cells and macrophages are recruited to th ....Tuberculosis (TB) remains an enormous problem worldwide and a continuing health problem in Australia. Most TB is not due to disease at the time of infection, but is a reactivation of dormant infection in people who have never eradicated the organisms. This study will investigate, in mice, how TB is initially contained within the lungs and how reactivation occurs. All mice infected with TB control the infection initially. T lymphocytes are activated and T cells and macrophages are recruited to the lung, migrate into lung tissue and surround infected lung macrophages forming granulomas. We have identified mice that progress to TB disease early after infection (early progressor strains) and another strain that progresses later (late progressors). In the early progressors, lymphocytes are not as efficiently recruited to the lung and do not form the tight granulomas seen in late progressor strains. We plan to make a detailed comparison of these two strains looking at differences in cell-membrane molecules and the soluble messenger molecules (cytokines and chemokines) that provide the signals that attract cells to the lung and direct them to surround infected lung macrophages. By comparing events in early and late progressor strains we will find which molecules are required for initial and long-term containment, and which events lead to breakdown of granulomas and reactivation of disease. In addition, we recently showed that one cytokine, tumour necrosis factor (TNF), is essential for cell migration through the lung. By comparing normal mice with mice deficient in TNF we will study the downstream effects regulated by TNF, particularly the chemokine messengers that direct cell movement into granulomas. By identifying the molecules and cells required to control TB we plan to design improved vaccines to prevent TB infection and improved treatments to prevent disease reactivation.Read moreRead less
Mechanisms of chronic infection, immunotolerance and coevolution in avian circovirus infections. This project will generate fundamental new knowledge into the pathogenesis of persistent, chronic viral diseases in a wide range of animal hosts. Furthermore, beak and feather disease virus is listed as a Key Threatening Process under the Endangered Species Protection Act (1992) to at least sixteen endangered Australian bird species. Very little is known about the host-virus interactions that occur d ....Mechanisms of chronic infection, immunotolerance and coevolution in avian circovirus infections. This project will generate fundamental new knowledge into the pathogenesis of persistent, chronic viral diseases in a wide range of animal hosts. Furthermore, beak and feather disease virus is listed as a Key Threatening Process under the Endangered Species Protection Act (1992) to at least sixteen endangered Australian bird species. Very little is known about the host-virus interactions that occur during the early stages of infection or why some birds recover yet others develop full blown disease. This project will provide new knowledge that can be used to counteract its effects on current and future endangered species recovery program.Read moreRead less
NOVEL THERAPEUTICS FOR AUTOIMMUNE DISEASE USING MOUSE SCREENING MODELS. The project aims to use experimental models of human autoimmune disease in the mouse for the testing of developmental isoflavonoid compounds produced by the Industry Partner, for protective effects against autoimmunity. The murine models proposed will duplicate human autoimmune cardiomyopathy, systemic lupus erythematosus and multiple sclerosis, encompassing both organ-specific and systemic autoimmune diseases. Isoflavonoi ....NOVEL THERAPEUTICS FOR AUTOIMMUNE DISEASE USING MOUSE SCREENING MODELS. The project aims to use experimental models of human autoimmune disease in the mouse for the testing of developmental isoflavonoid compounds produced by the Industry Partner, for protective effects against autoimmunity. The murine models proposed will duplicate human autoimmune cardiomyopathy, systemic lupus erythematosus and multiple sclerosis, encompassing both organ-specific and systemic autoimmune diseases. Isoflavonoid protection is anticipated from the antioxidant, anti-inflammatory and oestrogenic characteristics of these compounds/Read moreRead less
Devil Facial Tumour Disease: Cytogenetic Clues to Transmission and Development. Devil Facial Tumour Disease is a fatal cancer that is decimating Tasmanian devils. Preliminary work suggests that tumours from different animals have identical sets of highly abnormal chromosomes, including a giant marker chromosome. We will use DNA probes to 'paint' abnormal tumour chromosomes to discover markers for diagnosis, and identify genes contributing to tumour development and immune suppression. Most import ....Devil Facial Tumour Disease: Cytogenetic Clues to Transmission and Development. Devil Facial Tumour Disease is a fatal cancer that is decimating Tasmanian devils. Preliminary work suggests that tumours from different animals have identical sets of highly abnormal chromosomes, including a giant marker chromosome. We will use DNA probes to 'paint' abnormal tumour chromosomes to discover markers for diagnosis, and identify genes contributing to tumour development and immune suppression. Most importantly, we will test our hypothesis that tumours all arose from a single ancestral cancer cell that is transmitted between animals. A cellular transmission has frightening implications for spread of disease, but will allow us to develop appropriate therapeutic strategies to save a unique Australian marsupial from extinction.Read moreRead less