Structural Diversity And Evolution Of Variant-specific Surface Proteins In The Protozoan Parasite, Giardia
Funder
National Health and Medical Research Council
Funding Amount
$436,417.00
Summary
Giardia are well-known as a cause of travellers' diarrhoea, but our knowledge about these parasites remains rudimentary. Infections are common in Australia, especially in day-care centres and outback Aboriginal communities. The 1998 Sydney water crisis highlighted the necessity of monitoring reservoirs and reticulated water for contamination by faecal cysts of both human and animal origin. The aim of this project is to learn more about the 'coat' proteins which cover the organisms. These protect ....Giardia are well-known as a cause of travellers' diarrhoea, but our knowledge about these parasites remains rudimentary. Infections are common in Australia, especially in day-care centres and outback Aboriginal communities. The 1998 Sydney water crisis highlighted the necessity of monitoring reservoirs and reticulated water for contamination by faecal cysts of both human and animal origin. The aim of this project is to learn more about the 'coat' proteins which cover the organisms. These protect the parasites against digestion, enabling them to reside indefinitely within the intestine. However, the proteins are also the principal target of host immunity. Analysis of Giardia populations has shown that as many as 150-200 different coat proteins can be made. Although individual cells have coats comprised of only a single protein type, these can 'switch' spontaneously to production of another type - a phenomenon known as 'antigenic variation'. This process occurs slowly but continuously, giving rise to 'variants' which survive successive host responses (directed against each predominant coat type) and occupy the vacancies left by the destruction of their immediate forebears. It is important to gain information about the structural diversity of these variant-specific proteins (VSP), as any 'Giardia' vaccine is likely to require inclusion of each major type. It is also important to elucidate how the 'switching' process occurs, as this may provide clues as to how it might be interrupted. The project addresses both aspects.Read moreRead less
Polymicrobial Pathogenesis In A Murine Periodontitis Model.
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
Severe periodontal disease is a chronic inflammatory disease of the tooth's supporting tissues and is associated with specific pathogenic bacteria. The disease has a large economic burden and is a major public health problem. Three bacterial species have recently been shown to be closely associated with advanced periodontal disease in humans. One of these three bacterial species has been shown to produce periodontal disease in a mouse model of disease and the major proteins on the cell surface o ....Severe periodontal disease is a chronic inflammatory disease of the tooth's supporting tissues and is associated with specific pathogenic bacteria. The disease has a large economic burden and is a major public health problem. Three bacterial species have recently been shown to be closely associated with advanced periodontal disease in humans. One of these three bacterial species has been shown to produce periodontal disease in a mouse model of disease and the major proteins on the cell surface of this bacterium have been characterized. Further, in this mouse model it has been demonstrated that killed cells of the bacterium or the major surface proteins when used as a vaccine prevent development of disease. The purpose of the current proposal is to extend this work to include all three bacterial species that have been associated with disease in humans. The major surface proteins of all these bacterial species when grown together as high density polymicrobial complexes will be determined. Recent results have shown that in high-density, polymicrobial cultures bacteria communicate using signalling systems which can alter the expression of cell surface proteins associated with disease. The ability of the three bacterial species, when grown in polymicrobial culture, to cause periodontal disease in the mouse model will be determined. This will allow the determination of whether a single species and-or multispecies vaccine is capable of protecting against disease in this model. The significance of the work is that it will increase our understanding of the bacteria associated with periodontal disease and it may lead to the development of an effective vaccine to help prevent disease in humans.Read moreRead less
How Do Cross-reactive Memory B Cells Affect Influenza Vaccine Titers?
Funder
National Health and Medical Research Council
Funding Amount
$798,049.00
Summary
Influenza vaccines are updated frequently to protect against the highly variable influenza virus. Despite careful selection of vaccine viruses, most influenza vaccines provide only modest protection and protection is poor some years. In turn, the response to vaccination varies between individuals. This probably reflects complex and variable histories of influenza infection and vaccination. The project investigates how past influenza exposure influences vaccine responses and effectiveness.