Elucidating The Critical Roles Of ILC1, NK Cell And Innate Memory In Immune Protection
Funder
National Health and Medical Research Council
Funding Amount
$657,024.00
Summary
Natural killer cells are innate cells that provide first line defense against infection and cancer. The recent discovery of a novel innate cell population has modified our vision of the early events necessary for immune protection. Understanding the role of these cells is critical as they could represent viable therapeutic targets. We have developed unique mouse models to experimentally target this population to determine how they are generated and their role in combating infection and cancer.
Genetic And Biochemical Mechanisms Dysregulating CD4 T Cell Tolerance In Organ-specific Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$456,000.00
Summary
This project will analyse mechanisms that regulate CD4 T cells and normally prevent the immune system from attacking parts of our own body. Unknown errors in the control of T cells result in autoimmune diseases such as Type 1 diabetes, multiple sclerosis, and thyroid disease, where T cells damage or destroy vital organs. In order to develop rational, specific methods for treating and preventing these diseases, it is necessary to identify and understand the genetic and biochemical mechanisms that ....This project will analyse mechanisms that regulate CD4 T cells and normally prevent the immune system from attacking parts of our own body. Unknown errors in the control of T cells result in autoimmune diseases such as Type 1 diabetes, multiple sclerosis, and thyroid disease, where T cells damage or destroy vital organs. In order to develop rational, specific methods for treating and preventing these diseases, it is necessary to identify and understand the genetic and biochemical mechanisms that normally control T cell cell responses to self components, and how inherited defects lead these mechanisms to break down. The project focuses on defining how CD4 T cell regulation breaks down in two well established examples of inherited susceptibility to autoimmune disease. The direct action of autoimmune susceptibility genes will be determined at the level of the specific T cells responsible for autoimmune attack and in terms of the biochemical pathways within T cells that are dysregulated. By identifying the mechanisms and biochemical pathways that are dysregulated in autoimmune disorders, the results of this project will reveal targets for understanding and diagnosing autoimmune diseases and for developing new drugs or or vaccines to prevent T cells damaging vital organs and cure these diseases.Read moreRead less
Mechanisms Controlling Antibody Production By Modulating B Cell Antigen Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$536,628.00
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, or resul ....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, or result in uncontrolled B cell accumulation in lymphoma, leukemia and myeloma. 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, and that B cell accumulation is tightly limited. 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, immune deficiency, or lymphoma, and that may be able to be used as drug targets to cure these diseases.Read moreRead less
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
Delineating Aberrant Adaptive Immune Responses Due To Germline Mutations In The PI3K Signalling Pathway
Funder
National Health and Medical Research Council
Funding Amount
$975,476.00
Summary
Activation of immune cells is required to generate appropriate immune responses that protect is from disease caused by pathogens. The inability to receive the correct type of signals causes immunodeficiency. The PI3 kinase pathway is central to immune cell activation – and genetic errors in this pathwat compromise the functioning of immune cells. We will investigate the nature of these defects and pursue avenues of overcoming them using pharmacological inhibitors of the PI3K pathway.
An Exploration Of The Balance Between West Nile Virus Pathogenesis And Immune System Mediated Control
Funder
National Health and Medical Research Council
Funding Amount
$325,442.00
Summary
West Nile Virus (WNV) is a mosquito transmitted infectious disease that is emerging globally. Infection can lead to the development of fatal encephalitis and currently there is no vaccine available for human use. Killer T cells, a component of the immune system, are essential for viral clearance from the brain. This project aims to further explore WNV pathogenesis and whether killer T cells can be utilized to keep the infection localised and prevent the spread of the virus to the brain.
Chronic infectious diseases have a devastating effect on global health. HIV and Plasmodium falciparum both cause chronic disease and have evaded effective vaccine design. Vaccines rely on immune memory – the ability to clear an infection rapidly to a previously encountered pathogen. This proposal investigates the formation and dysfunction of immune memory in chronic infectious diseases, which will be vital for creating new and effective vaccines.
Identifying The Molecular Basis Of Memory B Cell Function And Human Immunoglobulin E Memory Via Hyper Immunoglobulin E Syndromes
Funder
National Health and Medical Research Council
Funding Amount
$96,009.00
Summary
Memory B cells generate rapid and potent antibody responses to known threats. The molecular basis for this is unknown, but defects increase the risk of infection, autoimmunity, and allergy. Autoimmunity and allergy are often mediated by a poorly understood antibody subclass, immunoglobulin E (IgE). My project will use emerging single-cell technologies to reveal the molecular mechanisms of antibody memory and IgE regulation, enabling the design of superior vaccines and immunomodulatory therapy.
Manipulating Antibody Production To Maximise Memory In Vaccine Responses
Funder
National Health and Medical Research Council
Funding Amount
$1,084,424.00
Summary
Our immune system provides protection from germs. The secretion of germ-specific proteins (antibodies) is an integral component of this defence and the basis of virtually all vaccines. Pandemics of Influenza and SARS-CoV-2 and failure to develop vaccines against HIV and Malaria remind us that our strategies need urgent improvement. Increasing our understanding of how our body defends us by specifically targeting foreign structures will reveal avenues for successful, rational vaccine development.