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Investigation Of The Roles Of Foxn1, Wnts And Autophagy In The Development And Function Of Thymic Epithelial Cells.
Funder
National Health and Medical Research Council
Funding Amount
$220,222.00
Summary
The immune system usually protects the body from infections. Occasionally, the immune system mistakenly recognises components of the body as foreign and attacks them, resulting in autoimmune diseases such as diabetes, multiple sclerosis and arthritis. An organ called the thymus is responsible for educating the immune system, and preventing autoimmune diseases. The proposed project will explore how the thymus develops, and how it teaches the immune system to ignore normal components of the body.
A T-cell Based Approach To Identifying Islet Antigens In Human Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$404,400.00
Summary
Autoimmune diseases arise when the immune system, which protects us from infections and cancer, attacks healthy tissues. Nobody knows why the immune system mistakes healthy for unhealthy tissue. The immune system's T cells are prime suspects because they play a central role in controlling the immune response. Hence, the aim of this work is to understand what human T cells see in healthy tissues that may lead them to cause autoimmune diseases like type 1 diabetes.
Functional Genomic Analysis Of NK And NKT Cell Immune Control Of Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$692,040.00
Summary
The major populations of white blood cells responsible for learned immunity to are the B cells, which make antibody against microorganisms like bacteria, and the T cells, which kill virally infected cells and help B cells produce antibody. The T and B cells occasionally attack the body s own tissues, resulting in autoimmune disease. These diseases include type 1 diabetes, lupus, and anaemia, and collectively represent the third commonest cause of morbidity and mortality in humans. The major reas ....The major populations of white blood cells responsible for learned immunity to are the B cells, which make antibody against microorganisms like bacteria, and the T cells, which kill virally infected cells and help B cells produce antibody. The T and B cells occasionally attack the body s own tissues, resulting in autoimmune disease. These diseases include type 1 diabetes, lupus, and anaemia, and collectively represent the third commonest cause of morbidity and mortality in humans. The major reason why autoimmunity occurs is thought to be due to a failure in the mechanisms responsible for controlling such unwanted responses. Two other populations of white blood cells are involved in this regulation, termed NK and NKT cells, each of which release important cell hormones. The current project is designed to test whether defects in NK and NKT cells lead to autoimmune disease. For this purpose a special strain of mice (NOD mice) will be used. The reasons for their selection are: 1) they are highly susceptible to a range of autoimmune diseases including diabetes, lupus and anaemia, and 2) we and others have found that they are deficient in both NK and NKT cells. The proposed experiments are divided into two groups, one designed to characterise the nature of the defects in these cells and the other to identify the genes responsible for them. In this way it should be possible to shed light on the genetic basis of autoimmune diseases in general. The approach to be used involves sophisticated techniques of genetic analysis, which require production of special congenic lines of mice. These mice are like NOD mice but carry in addition to NOD genes genetic regions from a non-autoimmune strain with the potential to correct the defects in NK and NKT cells. In this way, it should be possible to pinpoint the disease susceptibility genes involved in causation of autoimmunity and to work out how they affect NK and NKT cells.Read moreRead less
Induction Of Antigen-specific Tolerance Through Inhibition Of RelB Function In Dendritic Cells
Funder
National Health and Medical Research Council
Funding Amount
$421,980.00
Summary
This proposal builds on preliminary data showing the possibility that responses of the immune system to antigens can be suppressed by modifying cells known as dendritic cells using an inhibitory drug. The drug appears to be able to control the ability of dendritic cells to educate the immune system about antigens. When antigens presented continuously are harmful to the immune system, they produce diseases such as rheumatoid arthritis and allergies. The experiments to be undertaken specifically l ....This proposal builds on preliminary data showing the possibility that responses of the immune system to antigens can be suppressed by modifying cells known as dendritic cells using an inhibitory drug. The drug appears to be able to control the ability of dendritic cells to educate the immune system about antigens. When antigens presented continuously are harmful to the immune system, they produce diseases such as rheumatoid arthritis and allergies. The experiments to be undertaken specifically look at means to prevent and reverse diseases like rheumatoid arthritis through the use of dendritic cells.Read moreRead less
Neurological Manifestations Of Experimental Neuronal Voltage-gated Potassium Channel Autoimmunity.
Funder
National Health and Medical Research Council
Funding Amount
$65,148.00
Summary
Antibodies against neuronal voltage-gated potassium channels (VGKC) are seen in various neurological illnesses, most commonly epilepsy and memory loss. The role of VGKC antibodies in the development of brain disease will be studied by immunizing rabbits against VGKC and transferring these antibodies to mice.
Apoptotic Pathways In Pancreatic Beta Cells Leading To Type 1 Diabetes And Transplant Rejection
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
The destruction of insulin-producing beta cells in the pancreas by immune cells leads to the need for daily insulin injections in patients with type 1 diabetes. This project aims to understand how beta cells are destroyed. A knowledge of the process by which this occurs will indicate ways we can protect these cells. Our previous work has suggested strategies that may protect beta cells, and we aim to test these. Such protection may eventually allow beta cell replacement by transplantation.
Stem Cell Engineering To Establish Tolerance And Reverse Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$497,250.00
Summary
The immune system is designed to protect us from harmful invaders such as bacteria, viruses and parasites. It should not attack our own tissues. However, in certain individuals, the immune system does attack our own tissues leading to life threatening conditions such as diabetes, multiple sclerosis and rheumatoid arthritis. To date, there is no cure for autoimmune diseases. Treatment is designed to treat the destructive effects of the disease. A strategy for achieving a cure is to program the im ....The immune system is designed to protect us from harmful invaders such as bacteria, viruses and parasites. It should not attack our own tissues. However, in certain individuals, the immune system does attack our own tissues leading to life threatening conditions such as diabetes, multiple sclerosis and rheumatoid arthritis. To date, there is no cure for autoimmune diseases. Treatment is designed to treat the destructive effects of the disease. A strategy for achieving a cure is to program the immune system to remove the harmful immune cells. Autoimmune gastritis which leads to pernicious anaemia is an autoimmune disease which affects the acid secreting cells of the stomach. To get a better understanding of autoimmune diseases, animal models are often used. We use a number of mouse models of autoimmune gastritis which closely resembles the human disease and thus makes a very good working model. Using these models we are exploring novel techniques aimed at reversing or curing established disease. This relies on removing the disease causing cells from the body and re-programming the immune system so as not to produce these cells.Read moreRead less
Expression And Functions Of Leukocyte Immunoglobulin-like Receptor (LIR)-6 And LIR-4 In Inflammatory Arthritis (IA).
Funder
National Health and Medical Research Council
Funding Amount
$292,216.00
Summary
Rheumatoid arthritis (RA) that affects millions worldwide is characterised by uncontrolled activation of immune cells destroying ones own joints. The reasons for this excessive activation of cells are not known and existing treatments are limited to easing symptoms. We will study the role of new proteins named as Leucocyte Ig-like Receptors in regulating immune cell activation. Understanding mechanisms that control unwanted activation of immune cells is critical in preventing and treating RA.
Role Of The IFN-induced Helicase IFIH1 In Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$630,621.00
Summary
Type 1 diabetes (T1D) is presently the most common chronic disease of childhood and is increasing, with incidence in children under five doubling over the last five years. Recent findings indicate the ifih1 gene is important in T1D. Our research aims to establish the contribution of this gene to the disease. It is hoped that recognition of relevant pathological molecules will allow identification of risk factors for disease development and, ultimately, targets for therapeutic intervention.