The RgpA-Kgp Proteinase-adhesin Complex And Virulence Of Porphyromonas Gingivalis
Funder
National Health and Medical Research Council
Funding Amount
$527,310.00
Summary
Periodontitis is a bacterial-associated inflammatory disease of the supporting tissues of the teeth which can result in tooth loss. The disease is a major public health problem with a large economic burden. A bacterium Porphyromonas gingivalis has now been identified as a major causative agent of chronic periodontitis. We have identified a major virulence factor of P. gingivalis. This virulence factor is a complex of proteins, encoded by two genes, and is involved in binding and destruction of h ....Periodontitis is a bacterial-associated inflammatory disease of the supporting tissues of the teeth which can result in tooth loss. The disease is a major public health problem with a large economic burden. A bacterium Porphyromonas gingivalis has now been identified as a major causative agent of chronic periodontitis. We have identified a major virulence factor of P. gingivalis. This virulence factor is a complex of proteins, encoded by two genes, and is involved in binding and destruction of host tissue. When used as a vaccine in animal models the protein complex protects against P. gingivalis infection. Animal protective sera recognises a segment of the protein complex involved in binding to host substrates. The aim of this project is to continue this work on the characterisation of this complex and its role in virulence in an approach to ultimately develop a defined vaccine against P. gingivalis based on this protein complex, in particular the sequences involved in binding. The expected outcome of this research is the further biochemical characterisation of the RgpA-Kgp protein complex and its role in virulence as well as development of a defined vaccine prepared using recombinant DNA and chemical synthesis techniques that protects against P. gingivalis infection in animal models of disease.Read moreRead less
The Role Of Proteinase Inhibitor 9 In Cytotoxic Lymphocyte Function
Funder
National Health and Medical Research Council
Funding Amount
$820,136.00
Summary
Cytotoxic lymphocytes eliminate virus-infected or cancerous cells from the body. This is achieved by the release of powerful cytotoxins that kill the abnormal cell. Unless carefully targeted these cytotoxins can damage surrounding normal tissue or the cytotoxic lymphocyte itself, and lead to autoimmune disease. One of the most important cytotoxins is a protease called granzyme B. We have discovered a natural inhibitor of granzyme B that is present in cytotoxic cells and testis. Our studies are a ....Cytotoxic lymphocytes eliminate virus-infected or cancerous cells from the body. This is achieved by the release of powerful cytotoxins that kill the abnormal cell. Unless carefully targeted these cytotoxins can damage surrounding normal tissue or the cytotoxic lymphocyte itself, and lead to autoimmune disease. One of the most important cytotoxins is a protease called granzyme B. We have discovered a natural inhibitor of granzyme B that is present in cytotoxic cells and testis. Our studies are aimed at understanding the role of the inhibitor in human immune and reproductive function. We will also design and evaluate synthetic compounds based on the natural inhibitor that will enable us to easily measure granzyme B levels and control its activity.Read moreRead less
Proteinase Inhibitor 6: A Multifunctional Intracellular Serpin
Funder
National Health and Medical Research Council
Funding Amount
$217,435.00
Summary
We have discovered and characterized an unusual protease inhibitor that is widely distributed in the body. We have shown that the inhibitor is present in immune cells that are responsible for fighting bacterial infection, and that its role is probably to protect these cells against a powerful endogenous protease produced to destroy ingested bacteria. The inhibitor probably has additonal roles because it is present in developing and adult brain, skin and other blood cells. In these tissues we hav ....We have discovered and characterized an unusual protease inhibitor that is widely distributed in the body. We have shown that the inhibitor is present in immune cells that are responsible for fighting bacterial infection, and that its role is probably to protect these cells against a powerful endogenous protease produced to destroy ingested bacteria. The inhibitor probably has additonal roles because it is present in developing and adult brain, skin and other blood cells. In these tissues we have evidence that inhibitor regulates other, unidentified, proteases. The purpose of this grant is to identify these proteases, and to elucidate the physiological significance of the inhibitor by studying mice that lack it.Read moreRead less