Interrogation Of Two Novel Genetic Susceptibility Loci For Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$840,615.00
Summary
This proposal, from the Australia and New Zealand multiple sclerosis (MS) Genetics Consortium, aims to interrogate two new genes that it recently identified as predisposing for the development of MS. Both of the genes underlying these findings are also associated with risk of developing other autoimmune diseases such as type 1 diabetes, rheumatoid arthritis and Graves' disease.
Climate Change And Rural Communities: Integrated Study Of Physical And Social Impacts, Health Risks And Adaptive Options
Funder
National Health and Medical Research Council
Funding Amount
$611,599.00
Summary
Rural Australia has begun to experience climate change impacts - which will increase in future. Losses in farm yields, water supplies, property, community morale and family incomes have diverse health effects. We will study the separate and joint effects of climate change and associated extreme events (e.g., bushfires) on selected health outcomes. Using integrative methods, we will clarify the main influences on health risks, their future projections, and how best to intervene to lessen risks.
Epithelial cell surface mucins are large complex proteins found on the surface of all mucosal epithelial tissues, for example in the respiratory, gastrointestinal, reproductive and urinary tracts. Most bacterial and viral pathogens enter the body via mucosal tissues. We have recently demonstrated that mucin proteins are a vital component of initial defence against mucosal pathogens. Defects in these proteins probably predispose individuals to common chronic infective and inflammatory diseases. T ....Epithelial cell surface mucins are large complex proteins found on the surface of all mucosal epithelial tissues, for example in the respiratory, gastrointestinal, reproductive and urinary tracts. Most bacterial and viral pathogens enter the body via mucosal tissues. We have recently demonstrated that mucin proteins are a vital component of initial defence against mucosal pathogens. Defects in these proteins probably predispose individuals to common chronic infective and inflammatory diseases. The proposed research aims to explore the mechanims by which mucins protect from infection, with a focus on the gastrointestinal tract. Gastrointestinal infections remain one of the major causes of mortality in children in undeveloped countries. We believe that these proteins are a critical hereto unrecognised element of immunity and that the proposed studies will have broad significance for treatment and prevention of infection. Additionally, understanding the function of mucins could lead to the development of new drugs to treat epithelial inflammation such as that seen in inflammatory bowel diseases and respiratory diseases such as asthma and cystic fibrosis.Read moreRead less
Mechanisms Underlying Acute Changes In Lung Function And Airway Responsiveness Following Respiratory Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$444,878.00
Summary
This study will investigate the mechanisms responsible for the increased airway responsiveness seen during respiratory viral infections to the common viruses of influenza (flu) and respiratory syncytial virus (RSV). Respiratory viral infections alter lung function and increase airway responsiveness in man. In addition, respiratory viral infections early in life are a risk factor for the subsequent development of asthma. The mechanisms responsible for this are unknown. Both the infecting virus an ....This study will investigate the mechanisms responsible for the increased airway responsiveness seen during respiratory viral infections to the common viruses of influenza (flu) and respiratory syncytial virus (RSV). Respiratory viral infections alter lung function and increase airway responsiveness in man. In addition, respiratory viral infections early in life are a risk factor for the subsequent development of asthma. The mechanisms responsible for this are unknown. Both the infecting virus and host factors, such as age of infection, gender and genetic predisposition, are likely to be important. OUTCOMES and SIGNIFICANCE: These studies will provide a comprehensive assessment of the effects of acute viral respiratory infections on lung function and airway responsiveness using cutting edge techniques developed in our labs. The results will provide new insights into how these infections cause lung disease and may provide clues for new approaches to prevent the adverse effects of these common respiratory viral infections.Read moreRead less
Macrophage-regulated Tissue Remodelling In Endometrial Receptivity For Embryo Implantation And Pregnancy Success
Funder
National Health and Medical Research Council
Funding Amount
$456,779.00
Summary
Infertility and recurrent miscarriage affect 60-80 million couples globally, including 15% of couples in Australia. Moreover, 1 in 6 pregnancies is affected by pre-eclampsia, low birth weight or preterm labour. Infertility and other pathologies in pregnancy often result from failure of the maternal tissues to adequately support embryo implantation and development of the placenta, leading to insufficient nutritional support of the developing fetus. We have discovered in mice that disruption in th ....Infertility and recurrent miscarriage affect 60-80 million couples globally, including 15% of couples in Australia. Moreover, 1 in 6 pregnancies is affected by pre-eclampsia, low birth weight or preterm labour. Infertility and other pathologies in pregnancy often result from failure of the maternal tissues to adequately support embryo implantation and development of the placenta, leading to insufficient nutritional support of the developing fetus. We have discovered in mice that disruption in the populations of immune cells called macrophages within the uterine endometrial lining can reduce the receptivity of the endometrum to embryo implantation, and can lead to fetal growth retardation and impaired health after birth. The purpose of this project is to delineate the precise functions of macrophages in interacting with other cells in the endometrium to facilitate attachment of the embryo, its invasion into maternal tissues, and its access to an adequate blood supply as the placenta develops during early pregnancy. We will employ state of the art experimental strategies including genetic models to deplete endometrial macrophage populations in mice, and will then study the implications for changes in endometrial tissue structure and function. Furthermore we will investigate the long term consequences of early macrophage perturbations for the fetus and neonate after birth. This study will improve our understanding of how determinants of macrophage function such as infection and inflammatory conditions, male factors, nutrition and stress can impair fertility and compromise optimal pregnancy outcome in humans.Read moreRead less