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
This research is directed by a team of medical and basic scientists with expertise in mechanisms of inflammation relevant to human disease. The program will investigate the molecular and cellular events that are responsible for inflammation in the kidneys, joints and blood vessels which lead to diseases such as glomerulonephritis, arthritis and atherosclerosis. The aim of the research is to find new therapeutic targets which may be specific to certain organs or disease processes, in order to dev ....This research is directed by a team of medical and basic scientists with expertise in mechanisms of inflammation relevant to human disease. The program will investigate the molecular and cellular events that are responsible for inflammation in the kidneys, joints and blood vessels which lead to diseases such as glomerulonephritis, arthritis and atherosclerosis. The aim of the research is to find new therapeutic targets which may be specific to certain organs or disease processes, in order to develop more effective and selective treatments ofchronic inflammatory disease in humans.Read moreRead less
The Early Inflammatory Response To Virulent And Avirulent Influenza Viruses
Funder
National Health and Medical Research Council
Funding Amount
$252,761.00
Summary
Innate immune mechanisms are vital components of host defences against pathogens. In this proposal I aim to investigate the particular mechanisms that operate in early defence against influenza virus infection and compare the ability of virulent and avirulent virus strains to (i) be recognized by components of the innate immune system, and (ii) to trigger an early inflammatory response to infection. It is anticipated that virulent virus strains have adapted to avoid recognition by innate cells s ....Innate immune mechanisms are vital components of host defences against pathogens. In this proposal I aim to investigate the particular mechanisms that operate in early defence against influenza virus infection and compare the ability of virulent and avirulent virus strains to (i) be recognized by components of the innate immune system, and (ii) to trigger an early inflammatory response to infection. It is anticipated that virulent virus strains have adapted to avoid recognition by innate cells such as macrophages. By avoiding this route of uptake and destruction, the virus is free to infect and replicate in other cells of the respiratory tract. Furthermore, by evading macrophage entry, the virus avoids triggering the release of early inflammatory mediators from these cells and this may affect both the speed and the magnitude of the subsequent inflammatory response. This study will contribute to a greater understanding of factors involved in initiating and regulating inflammation in the respiratory tract following viral infection. Furthermore, the findings may provide new insights into mechanisms of virulence of influenza and other enveloped viruses.Read moreRead less
Elimination of the transplant waiting list is the ultimate goal of research into pigto-human xenotransplantation. The prospect of success has been improved recently by refinements in technology used to introduce genetic modifications in the pig, although the genes that will need to be expressed or deleted are still undecided. What is clear is that intravascular thrombosis, a critical mediator of rejection of pig xenografts, must be overcome. This project aims to investigate the use of anticoagul ....Elimination of the transplant waiting list is the ultimate goal of research into pigto-human xenotransplantation. The prospect of success has been improved recently by refinements in technology used to introduce genetic modifications in the pig, although the genes that will need to be expressed or deleted are still undecided. What is clear is that intravascular thrombosis, a critical mediator of rejection of pig xenografts, must be overcome. This project aims to investigate the use of anticoagulant gene expression to prevent intravascular thrombosis associated with xenograft rejection.Read moreRead less
Preclinical Development Of A Humanised Antibody To C5aR.
Funder
National Health and Medical Research Council
Funding Amount
$124,875.00
Summary
Complement factor C5a is one of the most potent inflammatory mediators in the body. We have developed a monoclonal antibody that blocks the C5a receptor in vitro, and completely shuts down disease in a mouse model of rheumatoid arthritis. We plan to develop this promising new antibody into a potent therapy to treat a range of chronic and acute inflammatory diseases. The antibody has been humanised and this will be tested in three models of inflammation (rheumatoid arthritis, sepsis and colitis) ....Complement factor C5a is one of the most potent inflammatory mediators in the body. We have developed a monoclonal antibody that blocks the C5a receptor in vitro, and completely shuts down disease in a mouse model of rheumatoid arthritis. We plan to develop this promising new antibody into a potent therapy to treat a range of chronic and acute inflammatory diseases. The antibody has been humanised and this will be tested in three models of inflammation (rheumatoid arthritis, sepsis and colitis) to determine the efficacy of the antibody, safety, the most effective dose, timing and route of administration. These studies are a necessary prelude to human clinical trials, which we hope to perform in approximately 24 months.Read moreRead less
The Role Of RasGRP4, A Mast Cell Specific Protein In Mast Cell Growth, Differentiation And Activation
Funder
National Health and Medical Research Council
Funding Amount
$580,433.00
Summary
Mast cells are cells found in the body which are strategically located at mucosal sites and skin where they form a very important barrier in the immune defence. Mast cells have been implicated in a range of inflammatory disorders such as asthma and more recently they have been shown to participate in immunity against bacteria, viruses and fungi. Although a lot of work has been performed to analyze how mast cells respond to different stimuli and what factors are important in their activation, the ....Mast cells are cells found in the body which are strategically located at mucosal sites and skin where they form a very important barrier in the immune defence. Mast cells have been implicated in a range of inflammatory disorders such as asthma and more recently they have been shown to participate in immunity against bacteria, viruses and fungi. Although a lot of work has been performed to analyze how mast cells respond to different stimuli and what factors are important in their activation, there is little work available concerning what in the mast cell controls it's ability to become a mast cell and not any other cell. We have identified a specific protein that has been designated RasGRP4 which is restricted to mast cells and has, we believe, an important role to play not only in guiding immature cells to become mast cells but also in controlling some of the important functions of mast cells. Understanding this molecule more extensively will give us a much better understanding of diseases that the mast cell is involved in such as asthma and other inflammatory disorders. In addition it may shed insights into how mast cells are involved in immunity against bacteria and viruses.Read moreRead less
I am an Immunologist interested in the role of B-lymphocytes, their survival and expression of a novel chemoreceptor in Autoimmunity. I also study the important role of Neuropeptide Y in modulating key immune functions.