The Control Of Autoimmunity Originating From Somatically Hypermutated B Cells
Funder
National Health and Medical Research Council
Funding Amount
$530,337.00
Summary
Our immune systems are capable of producing long-lived antibodies that can last a lifetime. Sometimes, this powerful process can however become abnormal and result in autoimmune diseases such as lupus. We have recently developed the first experimental mouse model that allows researchers to study this process in great detail. This funding will extend our initial observations by identifying the exact mechanisms by which important regulators of autoimmune disease act.
Nodal Function In Peripheral Neuroinflammatory Disorders: Target Antigens, Functional Significance And Treatment Response
Funder
National Health and Medical Research Council
Funding Amount
$605,172.00
Summary
Inflammatory neuropathies are autoimmune disorders which produce severe disability and represent a costly burden to the healthcare system, but the causes remain unknown. Recent evidence from our team suggests that antibodies against parts of the peripheral nerve at the node of Ranvier are involved. The project aims to identify these specific targets and monitor treatment responsiveness, stabilise nerve function and prevent persistent disability.
Development Of Clinical Algorithms To Diagnose And Predict Prognosis Of Food Allergy
Funder
National Health and Medical Research Council
Funding Amount
$136,636.00
Summary
Australia has the highest rate of food allergy internationally. Despite ongoing research into the area, there is currently no cure, with patient avoidance the most effective mode for the prevention of food allergy. A food challenge still the gold standard for food allergy diagnosis, and although definitive, is associated with a risk of anaphylaxis. My research aims to identify the biological differences between active disease and being healthy to develop novel diagnostic methods for food allergy
We have discovered how a rare type of human antibody called IgG4 exerts a major regulatory influence on the body's immune system. We have discovered how IgG4 can "switch" off inflammatory white blood cells which has broad implications for the development of new forms of therapy for switching off allergies and autoimmune diseases and for switching on immunity to infections and cancers.
Immunoglobulin Germline Genes, BCR Repertoire Development And Disease Susceptibility. An Investigation Of Haplotypic Variation Between Individuals
Funder
National Health and Medical Research Council
Funding Amount
$519,828.00
Summary
The immune system is capable of making a repertoire of protective antibodies including literally tens of millions of different specificities. These are produced by permutations and combinations of a small set of ‘germline’ genes. This project will analyse how individual variations in the germline genes lead to individual differences in the repertoires of available antibodies, and will investigate whether or not such differences contribute to our susceptibility to infection and autoimmune disease ....The immune system is capable of making a repertoire of protective antibodies including literally tens of millions of different specificities. These are produced by permutations and combinations of a small set of ‘germline’ genes. This project will analyse how individual variations in the germline genes lead to individual differences in the repertoires of available antibodies, and will investigate whether or not such differences contribute to our susceptibility to infection and autoimmune diseases.Read moreRead less
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.
Winter-only Treatment With Omalizumab To Prevent Asthma Exacerbations In Children.
Funder
National Health and Medical Research Council
Funding Amount
$738,855.00
Summary
Acute exacerbations of asthma add considerably to the economic and social burden imposed by asthma. Current asthma treatment frequently controls underlying asthma but does not prevent acute exacerbations in exacerbation-prone asthmatics. This trial, based on our asthma research, provides new hope that acute asthma can be prevented.
Our bodies rely on the production of potent, or ‘high affinity’, antibodies to fight infection. We have found that antibody responses are unexpectedly boosted following the depletion of a specific subset of immune cells. This is especially true for B cells that are poor antibody producers. Our findings are likely to be relevant to (1) the design of vaccines to infectious agents that have important CTL and antibody components (e.g. HIV), (2) for the improved production of antibody for therapeutic ....Our bodies rely on the production of potent, or ‘high affinity’, antibodies to fight infection. We have found that antibody responses are unexpectedly boosted following the depletion of a specific subset of immune cells. This is especially true for B cells that are poor antibody producers. Our findings are likely to be relevant to (1) the design of vaccines to infectious agents that have important CTL and antibody components (e.g. HIV), (2) for the improved production of antibody for therapeutic use (e.g. cancer).Read moreRead less
Modeling Human Actin Related Protein 2/3 Complex Subunit 1B (ARPC1B) Deficiency In Mice
Funder
National Health and Medical Research Council
Funding Amount
$755,005.00
Summary
The actin cytoskeleton forms the structure that not only keeps cells in their normal shape but is also essential for the movement of cells and for interaction between cells. We have recently identified the first patients with an immunodeficiency caused by a defect in a gene called ARPC1B, which plays a crucial role in the regulation of actin. Through the investigation of novel mouse models we will elucidate the pathomechanism underlying the disease of these patients.
Investigation Of Cellular Abnormalities And Synapse Formation In DOCK8 Immunodeficiency
Funder
National Health and Medical Research Council
Funding Amount
$318,284.00
Summary
Why do some people get allergies? Or serious infections? To investigate this we will study mice and humans with a mutation in the DOCK8 gene. People with mutations in the DOCK8 gene get Hyper-IgE Syndrome and develop severe viral infections of the skin as well as allergic disease. By investigating how DOCK8 works in the cells of the immune system, we hope to understand why these infections and allergies occur and find out why these problems can also happen in those without this specific genetic ....Why do some people get allergies? Or serious infections? To investigate this we will study mice and humans with a mutation in the DOCK8 gene. People with mutations in the DOCK8 gene get Hyper-IgE Syndrome and develop severe viral infections of the skin as well as allergic disease. By investigating how DOCK8 works in the cells of the immune system, we hope to understand why these infections and allergies occur and find out why these problems can also happen in those without this specific genetic defect.Read moreRead less