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The Regulation Of IgE Antibody Production By Antigen-specific B Cells
Funder
National Health and Medical Research Council
Funding Amount
$454,105.00
Summary
Asthma and other allergies are caused by the inappropriate production of IgE antibodies by the immune system. IgE is not produced in response to most infections but the controls that normally prevent IgE production are unknown. We have identified two separate molecules that prevent IgE production during immune responses. In this proposal we aim to investigate how these controls work. This information may help to devise strategies for controlling IgE production and therefore allergic disease.
Identification Of Antigen Selection In The Human IgE Response By Analysis Of Somatic Point Mutations
Funder
National Health and Medical Research Council
Funding Amount
$256,973.00
Summary
Allergic disease affects over 25% of the Australian community. It is responsible for significant sickness and death, particularly amongst children, and its incidence is on the increase. The reasons for this, and the underlying causes of allergic disease, remain unclear. Allergic disease results from the actions of molecules called IgE antibodies, which are also associated with parasitic infection. Even in these conditions, where IgE concentrations are raised in the blood, the concentrations are ....Allergic disease affects over 25% of the Australian community. It is responsible for significant sickness and death, particularly amongst children, and its incidence is on the increase. The reasons for this, and the underlying causes of allergic disease, remain unclear. Allergic disease results from the actions of molecules called IgE antibodies, which are also associated with parasitic infection. Even in these conditions, where IgE concentrations are raised in the blood, the concentrations are too low to allow their direct study. We have recently applied molecular biological techniques to study the genes that encode IgE antibodies. Our work suggests that the IgE response can sometimes develop in a different way to that of other antibodies (eg IgG). On the other hand, laboratory (in vitro) studies over many years support the possibility that IgE and IgG develop in parallel. In this study, we wish to identify circumstances in which IgG-like IgE antibodies develop. We therefore wish to study patients with different kinds of allergic disease, and patients with other conditions that are associated with IgE production. We therefore wish to study patients who have infections with parasitic worms. We deduce the processes that give rise to IgE antibodies by analysing patterns of mutations that accumulate in antibody genes during an immune response. Over recent years, we have developed new approaches to the analysis of such mutations, and this project also seeks to further develop our mutation analysis. This more powerful analysis will be applied to the study of mutations in the IgE genes seen in different patient groups, and should allow us to quantify the proportion of IgE antibodies that develop in each way. A better understanding of the relative contributions of the two pathways to IgE, in different conditions, will transform our understanding of the IgE response, and open up new avenues for the investigation of the causes and treatment of allergic disease.Read moreRead less
Environmental Regulation Of Virulence In Attaching And Effacing Enterobacteria
Funder
National Health and Medical Research Council
Funding Amount
$569,063.00
Summary
Disease-causing bacteria must respond to the extreme conditions, such as acid and bile, which they encounter in their hosts. They achieve this by sensing their environment and activating genes that enhance their survival and ability to cause disease. In this project we will define the mechanisms by which these sensing and response pathways occur, using E. coli as a model. The information obtained from this research should lead to new strategies to treat and prevent bacterial infections.
Characterisation Of A Newly-discovered, Virulence-associated, Protein Secretion System Of Enteropathogenic E. Coli
Funder
National Health and Medical Research Council
Funding Amount
$582,149.00
Summary
The cell walls of bacteria act as a barrier to the export of any proteins they produce. We recently discovered a protein secretion system, which diarrhoea-causing strains of E. coli require to cause disease. The aim of this study is to characterise this secretory system, and discover how it functions and what it secretes. The knowledge obtained from this research will shed new light on how E. coli causes disease and could reveal novel methods to treat and prevent infections with this bacterium.
Virulence Strategies Of LEE-negative Shiga Toxigenic Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$230,246.00
Summary
Shiga toxigenic Escherichia coli (STEC) are a diverse group of pathogens that cause serious gastrointestinal disease in humans, which can lead to life-threatening complications. This project is aimed at understanding how these bacteria cause disease, and is focused on a subset of STEC strains that are highly virulent and produce a novel cytotoxin. A better understanding of the pathogenic mechanisms of STEC is essential for development of improved therapeutic and preventative strategies.