The Impact Of Influenza A Virus PB1-F2 Protein On Host Immunity And The Potential For Therapeutic Targeting
Funder
National Health and Medical Research Council
Funding Amount
$317,076.00
Summary
The 1918 influenza virus pandemic resulted in 50 million deaths globally and there is potential for new pandemics, such as the predicted H5N1 Bird Flu . Exact causes of such devastating lethality are not fully identified. Newly discovered influenza A virus (IAV) PB1-F2 protein is present in nearly all highly pathogenic IAVs and promotes virus virulence. This study will further examine the way in which PB1-F2 impacts the host, revealing potential therapeutic targets to lessen disease burden.
Cell Surface Mucins In Gastrointestinal Infection And Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$591,967.00
Summary
Mucosal tissues, such as the gastrointestinal and respiratory tracts, are the most common site of infectious disease. We have found that the cells in these tissues produce molecules on their surface, known as mucins, that protect from infection. In the case of chronic infection the mucins prevent the inflammation that underlies the development of cancer. In this project we will be exploring the mechanisms by which mucins prevent infection and inflammation.
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
The Role Of Apoptosis In Pathogenesis And Immunology Of Salmonella Infections
Funder
National Health and Medical Research Council
Funding Amount
$276,988.00
Summary
Salmonellae are important human pathogens in developed and developing countries. The most severe salmonella disease, typhoid fever, is becoming more difficult to treat because of increasing antibiotic resistance. In addition, current vaccines only provide short-term protection. The studies in this proposal are designed to answer important questions about immunity against typhoid fever, including how this immunity is provoked, and the direct and indirect causes of pathology in the disease. The fo ....Salmonellae are important human pathogens in developed and developing countries. The most severe salmonella disease, typhoid fever, is becoming more difficult to treat because of increasing antibiotic resistance. In addition, current vaccines only provide short-term protection. The studies in this proposal are designed to answer important questions about immunity against typhoid fever, including how this immunity is provoked, and the direct and indirect causes of pathology in the disease. The focus of this project is the induction of host cell apoptosis, an important virulence mechanism shared by many bacteria and viruses. The research will have direct application to human typhoid and may lead to novel therapies and improved vaccines for typhoid fever.Read moreRead less
Otitis Media In Indigenous And Non-Indigenous Children: Microbiological And Immunological Risk Factors
Funder
National Health and Medical Research Council
Funding Amount
$534,400.00
Summary
Otitis media (middle ear infections) is a major health problem in children. Many children suffer repeated attacks requiring frequent courses of antibiotics, some need surgery and some suffer serious consequences, particularly hearing loss. This can affect performance at school, hence employment and social circumstances in adulthood. Indigenous children suffer much higher rates of disease with more complications than non-Indigenous children. Many factors predispose to the heavy burden of disease. ....Otitis media (middle ear infections) is a major health problem in children. Many children suffer repeated attacks requiring frequent courses of antibiotics, some need surgery and some suffer serious consequences, particularly hearing loss. This can affect performance at school, hence employment and social circumstances in adulthood. Indigenous children suffer much higher rates of disease with more complications than non-Indigenous children. Many factors predispose to the heavy burden of disease. In the Kalgoorlie-Boulder area we are following Indigenous and non-Indigenous children from birth to 24 months to look at a broad range of factors in order to proceed as soon as possible to appropriate intervention programs. Samples from the back of the nose are collected to find out the relationship between carriage of a range of bacteria or viruses and risk of getting otitis media. Information on antibiotic resistance of the bacteria we isolate will assist in ensuring appropriate treatment of otitis media. We also collect a sample of breast milk from mothers and several samples of saliva to find out about the immune system of babies and how this relates to disease to assist in an ongoing program of vaccine development for prevention of otitis media. We will find out how environmental factors such as crowding or passive smoking relate to carriage of bacteria and whether a combination of different factors increase risk of disease. A new vaccine called pneumococcal conjugate vaccine, recently licensed in Australia, is highly effective in preventing severe diseases such as pneumonia and meningitis and affords some protection against ear infections. It is likely to be offered first to Indigenous children because they suffer very high rates of pneumococcal disease. The vaccine may alter the types of bacteria in the nose. This needs to be monitored carefully which will be possible during this study.Read moreRead less
Development Of A Vaccine For Genital Chlamydia Infections: Protection Against Transmission And Disease Pathology
Funder
National Health and Medical Research Council
Funding Amount
$322,245.00
Summary
Genital Chlamydia infections are the most common sexually transmitted infection in Australia with annual health costs of 90-160 million dollars. Ifection rates in 15-29 year olds are increasing at 15-20% per year. Antibiotics are currently the treatment of choice, however antibiotic resistance is increasing and most infections are asymptomatic and not treated in the absence of screening programs. The project aims to develop a genital Chlamydia vaccine using a combination of novel antigens.
Enhancement Of Mucosal Immunity And CTL Avidity Against HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$553,070.00
Summary
Production of strong antiviral immunity at the local mucosa (genito-rectal track) is essential for protection against HIV-AIDS. We believe that expression of small hormone-like molecules known as Th2 cytokines IL-4-IL-13 negatively influence the generation of protective immunity against HIV. Thus we aim to counteract these effects by co-expressing proteins known as chemokines together with vaccine antigens to improve the quality of mucosal vaccine immunity.
IgA Mediated Activation Of FcalphaRI, An Fc Receptor And A Leukocyte Ig-like Receptor.
Funder
National Health and Medical Research Council
Funding Amount
$535,500.00
Summary
Our immune system exists to seek and destroy infections caused by bacteria and viruses (pathogens) that would grow in us. B cells in the immune system make antibody tags which attach to pathogens marking them for elimination. A special type of antibody is IgA. IgA occurs in two forms, the first is found at mucosal sites, these are membranous passages in the body, such as the lung, the gut and the genital tract. These communicate with the outside and are the major route of pathogen entry into the ....Our immune system exists to seek and destroy infections caused by bacteria and viruses (pathogens) that would grow in us. B cells in the immune system make antibody tags which attach to pathogens marking them for elimination. A special type of antibody is IgA. IgA occurs in two forms, the first is found at mucosal sites, these are membranous passages in the body, such as the lung, the gut and the genital tract. These communicate with the outside and are the major route of pathogen entry into the body. Here IgA forms a rather passive, but pathogen specific, sticky barrier to prevent microbial pathogens attaching to these large surfaces. In an everyday analogy this IgA behaves somewhat like fly-paper. This subdued response is appropriate as we are constantly exposed to micro-organisms living in our gut, or breathed into our lungs, and our immune system would make us ill if it aggressively attacked our innocuous microbial neighbours. The second type of IgA is found in the blood where it attaches to pathogens that have breached the body's barriers. These IgA tags are actively sought by white blood cells whose function is to protect the body from infection by recognising and engulfing the tagged pathogens and destroying them with killer molecules, including bleach. The IgA-Fc receptor is the sensor on the surface of white blood cells which seeks the IgA tags as they attach to pathogens. In order to survive in this hostile environment some of our pathogens, such as Staphylococcus, have their own strategies to make themselves invisible to the immune system. These strategies include cutting up the IgA tags or blocking the sensors for IgA. In this project we will study how IgA tags turn on white blood cells to destroy pathogens. We will also be looking at two Staphylococcal proteins which block up the sensor for IgA tags. Finally we are endeavouring to understand how it is the mucosal type IgA does not activate the white cells nearly as much as the IgA from the blood.Read moreRead less
Acupuncture And Mucosal Immunity In The Upper Respiratory Tract
Funder
National Health and Medical Research Council
Funding Amount
$383,082.00
Summary
Many Australians seek complementary and alternate medicine for the treatment of allergic diseases such as allergic rhinitis. There is evidence that acupuncture treatment is clinically beneficial for the treatment of allergic rhinitis. This project will produce new information that will provide a scientific basis of how acupuncture influences the immune response and modulates inflammation. Broader application to other inflammatory diseases and therapeutic interventions is possible.