Differences In Neonatal Immune Regulation In The Developing And Developed World: Implications For Neonatal Vaccinations?
Funder
National Health and Medical Research Council
Funding Amount
$332,083.00
Summary
This project will study the effect of adverse living conditions such as high microbial exposure, malnutrition, environmental tobacco smoke and malaria infection on the development of a newborn's immune system,by comparing immune response between newborns in Papua New Guinea and in Western Australia. This study will help us to understand the high susceptibility of children in the developing world for infectious diseases and to develop better prevention strategies.
This study combines sophisticated molecular techniques with state-of-the-art biochemical and physiological analyses to determine how gut hormones regulate satiety. By utilising unique conditional and germline KO mice , this research will make highly original and internationally competitive contributions to the understanding of the regulation of satiety and energy expenditure. Knowledge as to the causes of lack of satiety will be of great benefit in the search for novel treatments for obesity.
Glomerulonephritis (Bright's Disease) is the commonest cause of destruction of kidney function that leads to patients requiring artificial kidney treatment (dialysis) and renal transplantation. The glomeruli or filters of the kidney are attacked by inflammation and destroyed. The attack is usually auto-immune, that is the bodys' immune system loses tolerance to kidney tissue and mounts a destructive attack on the glomeruli. In many patients, this attack is mild and resolves with current treatmen ....Glomerulonephritis (Bright's Disease) is the commonest cause of destruction of kidney function that leads to patients requiring artificial kidney treatment (dialysis) and renal transplantation. The glomeruli or filters of the kidney are attacked by inflammation and destroyed. The attack is usually auto-immune, that is the bodys' immune system loses tolerance to kidney tissue and mounts a destructive attack on the glomeruli. In many patients, this attack is mild and resolves with current treatments to dampen the immune response. In others, current treatment is inadequate to dampen the attack and the kidney is destroyed. This research uses experimental models of nephritis to examine how the immune system injures the glomeruli. In particular, how T cells attack and mediate injury. This is a novel concept, as hither to it has been thought antibodies and other factors in the blood (complement) mediate injury. Our group was one of the first to identify T cells mediate injury in forms of glomerulonephritis, previously thought to be solely mediated by antibody and complement. This project will further define which molecules produced by the T cell effect injury of glomeruli. With the potential aim of turning off the T cell attack mechanisms in a more specific way than is achieved by non specific immunosuppressive drugs such as corticosteroids, cytotoxic (anti-cancer) drugs or cyclosporine (an anti-rejection drug). A major part of this project will be to examine the role of cytokines, hormone like molecules that are produced by white cells and mediate injury or regulate other white cells, in effecting injury and in turning off the immune injury.Read moreRead less
Occupational Exposure To Lead Compounds And Human Cancer
Funder
National Health and Medical Research Council
Funding Amount
$222,887.00
Summary
This study aims to investigate whether there is a link between cancer (in particular cancer of the stomach, lung, kidney and central nervous system) and occupational exposure to lead compounds. There are only a few published cohort studies available on occupational exposures in use and applications of lead compounds, despite the widespread use of these compounds in the past 50 years. Since the late 1980s the use of lead compounds in Australia has decreased, but Australian and world lead producti ....This study aims to investigate whether there is a link between cancer (in particular cancer of the stomach, lung, kidney and central nervous system) and occupational exposure to lead compounds. There are only a few published cohort studies available on occupational exposures in use and applications of lead compounds, despite the widespread use of these compounds in the past 50 years. Since the late 1980s the use of lead compounds in Australia has decreased, but Australian and world lead production has increased. Australia is the world's biggest producer of lead. The precise number of lead workers worldwide is unknown but there are likely to be more than 2 million workers of which many are in developing countries where control of lead exposure is unsatisfactory and occupational exposure limits are considerably higher than in developed countries. Evidence for or against cancer risk with exposure to lead compounds , in particular inorganic lead, will therefore have implications for many Australian and international workers. This is also important for health risk assessment for environmental contamination in the Australian community. In our study we will review the state government archived records of about 8,000 lead workers in New South Wales, Victoria and South Australia, who took part in lead compound exposure surveys and had blood tests in the 1970s, 1980s and 1990s, as part of government lead regulations in force at the time. We will then match the details of these workers against the National Cancer and Death registry data to calculate cancer rates. This should involve a sufficient number of workers to enable us to undertake a comprehensive health evaluation of cancer risk and exposure to lead compounds.Read moreRead less
Modification Of Dendritic Cell Function And Priming Of Protective Immunity By Malaria Blood-stage Parasites
Funder
National Health and Medical Research Council
Funding Amount
$316,500.00
Summary
Approximately 2 billion individuals live in areas where malaria is a risk. Children and naive individuals who get infected for the first time, usually travellers, are most at risk of dying from a Plasmodium falciparum infection, with an estimated 2 million children under 3 years of age killed each year. Surviving adults living in malarial areas have partial immunity after a series of infections. It is unclear how this protective immunity, particularly cellular immunity is acquired, and also uncl ....Approximately 2 billion individuals live in areas where malaria is a risk. Children and naive individuals who get infected for the first time, usually travellers, are most at risk of dying from a Plasmodium falciparum infection, with an estimated 2 million children under 3 years of age killed each year. Surviving adults living in malarial areas have partial immunity after a series of infections. It is unclear how this protective immunity, particularly cellular immunity is acquired, and also unclear why it takes so long to develop. Recent advances in immunology have indicated that Dendritic Cells (DCs) are necesssary to induce effectively cellular immunity and prime memory responses. DCs take up foreign proteins and show them to T cells resulting in their activation. T cells are critical for the establishment of long-term protective immunity to malaria. However, it has not been known if DC can take up malaria parasites or malaria infected red-blood cells and process them to activate protective T cell responses. Our preliminary data shows that both human and mouse DC can take up parasitised red-cells, but that the interaction of parasite derived proteins on the surface of the red cell with DC receptors causes a defect in DC maturation. This defect may prevent effective priming of T cells during natural malaria infection, contributing to the poor development of immunity in malaria endemic areas. Given these novel fundamental findings, it is now important to elucidate: 1) The nature of the DC defect induced by the parasites 2) Assess whether this is a common feature of all Plasmodia, or whether it may relate to strain virulence 3) Determine the nature and extent of the malaria specific response induced by the defective DC. Understanding how parasites may be able to sabotage a critical inducing component of the immune system has wide implications for the use of any immuno-therapies in malaria endemic regions.Read moreRead less
Anogenital Human Papillomavirus Infection And Its Outcomes In Men
Funder
National Health and Medical Research Council
Funding Amount
$333,433.00
Summary
Anal human papillomavirus (HPV) infection is common in homosexual men. Low risk types cause anal warts and high risk types of HPV cause anal cancer. This study will determine incidence and risk factors for HPV infection in a cohort of young homosexual men, the association of anal warts treatment with HIV risk, and the specific association of HPV subtypes with anal cancer. The findings of this research will help delineate the potential benefits of HPV vaccination in this population.
Understanding The Health Effects Of Biomass Smoke In Australian Towns And Cities
Funder
National Health and Medical Research Council
Funding Amount
$172,392.00
Summary
Wildfires have become more frequent and severe the world over and the health impacts of the associated air pollution is a major gap in the current evidence. Working with lead agencies in air quality regulation, public health and fire management I will examine and compare the health effects of air pollution from deliberate burns, bushfires, wood heaters and other sources of air pollution. The research will focus on respiratory and heart disease to inform public health and individual patient care.