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Dissecting Human B-cell Function: From Primary Immunodeficiencies To Chronic Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
Despite knowing a lot about immunity in a mice, functional analysis of the human immune system has been a major challenge. I will study defects of immune cells in humans with gene mutations that cause an antibody deficiency. With new insights from these unique clinical samples, I will functionally dissect human immune responses, directly translate these to chronic inflammatory disease, and provide implications for future vaccine development and cancer treatment.
Lymphocyte Differentiation And Genetics Of Primary Immunodeficiency
Funder
National Health and Medical Research Council
Funding Amount
$143,676.00
Summary
Primary immunodeficiency diseases affect a large number of individuals. Due to abnormal immune responses, these people are at risk of frequent, severe infections, as well as complications of autoimmune disease and cancer. Treatment often involves regular immunoglobulin (antibody) replacement. Through a better understanding of the mechanisms underlying these immunodeficiency diseases, we hope to be able to determine genetic causes, and more cost-effective and targeted treatment options.
This Program Grant brings together a world-leading team of experts to elucidate mechanisms that protect most people from infection by making antibodies, and their failure caused by genes or infections like influenza or HIV. The team will determine mechanisms that protect most people from making antibodies against normal parts of our body, whose failure causes numerous autoimmune diseases including rheumatoid arthritis. The team will develop ways to engineer better antibodies.
Autoimmunity In Double Transgenic Models Of Self Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$157,660.00
Summary
The immune system protects the body against infection by means of a population of circulating white blood cells called lymphocytes. Each lymphocyte has on its surface its own particular receptor which recognises only one out of the universe of possible substances. Receptors are generated in a semi-random way, using a combination of elements encoded by the genes, and it is possible to generate receptors that react with the body itself, rather than with invading organisms. If the cells bearing the ....The immune system protects the body against infection by means of a population of circulating white blood cells called lymphocytes. Each lymphocyte has on its surface its own particular receptor which recognises only one out of the universe of possible substances. Receptors are generated in a semi-random way, using a combination of elements encoded by the genes, and it is possible to generate receptors that react with the body itself, rather than with invading organisms. If the cells bearing these self-reactive receptors become activated, an autoimmune disease ensues. We are using animal models to study how the body deals with self-reactive cells. We will attempt to activate these cells and thus cause autoimmune disease. The experimental manoeuvres that successfully cause autoimmunity in normal animals will provide clues as to the processes that can cause autoimmune disease.Read moreRead less
Integrating Drug Delivery Principles Into Drug Design To Transform The Treatment Of Immune Disease
Funder
National Health and Medical Research Council
Funding Amount
$552,635.00
Summary
Immune system disorders (e.g. rheumatoid arthritis, transplant rejection, Crohn’s disease, multiple sclerosis) are often treated with immunosuppresant drugs. However, immunosuppressant drugs can cause significant toxicity and can lack efficacy. This proposal will show how the design of drugs used to treat immune disorders can be changed to allow drugs to be delivered specifically to their site of action (immune cells) thereby enhancing activity and reducing toxicity.
Mechanisms Controlling Antibody Production By Modulating B Cell Antigen Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$452,125.00
Summary
This project will analyse mechanisms that regulate antibody production in health and disease. In health, antibodies are normally made exclusively against infectious agents, providing long-lasting immunity. Unknown errors in the control of antibody production result in autoimmune diseases such as systemic lupus or rheumatoid arthritis, where antibodies are made against parts of our own bodies, or result in allergies where antibodies are made against innocuous elements of our environment. In order ....This project will analyse mechanisms that regulate antibody production in health and disease. In health, antibodies are normally made exclusively against infectious agents, providing long-lasting immunity. Unknown errors in the control of antibody production result in autoimmune diseases such as systemic lupus or rheumatoid arthritis, where antibodies are made against parts of our own bodies, or result in allergies where antibodies are made against innocuous elements of our environment. In order to develop rational, specific methods for treating these diseases, it is necessary to identify and understand the biochemical mechanisms that normally control antibody formation against infectious agents, self components, and innocuous environmental agents. The project focuses on defining the biochemical mechanisms by which the antibody-forming cells, B lymphocytes, sense infectious, innocuous, or self components. These cells carry specific receptors that bind these components and transmit signals into the B lymphocyte. The research will determine how different types of signal are transmitted by the receptor so that, normally, large amounts of antibody are made against infectious agents but very little antibody is made against self components. By identifying how the types of signals are changed, the results of this project will reveal control mechanisms that may be altered in autoimmunity, allergy or immune deficiency, and that may be able to be used as drug targets to prevent unwanted antibody production to cure these diseases.Read moreRead less
Follicular Helper T Cell Development And Function: From Mechanisms To Application
Funder
National Health and Medical Research Council
Funding Amount
$401,361.00
Summary
Antibodies are the basis of most successful vaccinations. Diminished antibody responses lead to immunodeficiency while excessive antibody responses contribute to autoimmune diseases. We are studying a newly identified specialised helper T cell subset, termed follicular helper T cells, which is essential to regulate the high-affinity and long-lived antibody responses. The knowledge should provide new strategies to design better vaccines, to control infections, or to treat autoimmune disorders.
The Regulation And Differentiation Potential Of Human Memory B Lymphocytes
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Antibody produced by our immune system plays a critical role in protecting us from infectious disease. Remarkably our ability to make antibodies is much faster the second time we see the infection. This memory of the previous attack occurs due to the formation of memory B cells that circulate in the blood, sometimes for years, looking for the same intruders. If they detect the infection they rapidly become activated and remake the antibody. These memory cells are very important for our protectio ....Antibody produced by our immune system plays a critical role in protecting us from infectious disease. Remarkably our ability to make antibodies is much faster the second time we see the infection. This memory of the previous attack occurs due to the formation of memory B cells that circulate in the blood, sometimes for years, looking for the same intruders. If they detect the infection they rapidly become activated and remake the antibody. These memory cells are very important for our protection. Vaccines operate by tricking the immune system into making these memory cells, even though the body hasn't seen the actual disease. Although clearly vital for our health little is known about the activation and antibody production by human B memory cells. This project will redress our lack of knowledge by performing a comprehensive evaluation of the properties of this important cell type.Read moreRead less