How BANK1 Pathway Defects In B Cells Cause Human Lupus
Funder
National Health and Medical Research Council
Funding Amount
$1,316,839.00
Summary
Autoimmune diseases affect 1 in 20 Australians and are incurable. To find effective therapies, we need to understand the genes that cause disease in humans. We have sequenced the entire genome of patients with an autoimmune disease and found several patients carrry two mutations in genes important for activation of B cells and shown these mutations cause disease. We plan to understand how these genes prevent autoimmunity, and to identify the best treatment for patients with these mutations.
Targeting Autophagy As A Means Of Control Of Cytokine Production In SLE
Funder
National Health and Medical Research Council
Funding Amount
$616,518.00
Summary
Systemic lupus erythematosus (SLE, or lupus) is a common immune disease that causes organ damage and loss of life, chiefly affecting young women. There is no cure for SLE. We have discovered that a natural process called 'autophagy' could be a way to limit inflammation during SLE. In this project we will discover whether this could lead to a new way to treat this disease.
Molecular Signatures Of Public Clonotypes In Human Systemic Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$540,633.00
Summary
New platform technology has been developed to study autoantibody clones in lupus and Sjogren's syndrome. This approach has furthered our understanding of these disorders by the discovery of unique sets of clones that are common to all patients. The unique "molecular signatures" of these clones can be translated to a next-generation diagnostic that detects them in patients at extremely low levels missed by conventional tests.
Determining The Essential Regulators Of Antibody Production
Funder
National Health and Medical Research Council
Funding Amount
$768,612.00
Summary
Plasma cells produce the antibodies that are essential to protect us from pathogenic microorganisms and provide the basis for the beneficial effects of vaccination. Plasma cells can also cause disease through the production of antibodies against our own body, for example in Lupus and in the blood cell cancer multiple myeloma . Our research aims to understand the genetic regulation of antibody production, with an aim to "switch off" inappropriate antibody supply in disease.
The Axis Of Bcl-2, Plasmacytoid DCs And Lupus As A Basis For Therapy
Funder
National Health and Medical Research Council
Funding Amount
$712,172.00
Summary
Systemic lupus erythematosus (SLE) affects 1 in 1000 Australians, mostly women. Here the immune system goes awry and makes antibodies against the body’s own components including the body’s DNA. This leads to damage to many parts of the body including kidneys, joints, brain and heart. It is incurable. A particular immune cell controls the development of this disease and we have found this cell is selectively killed by an inexpensive drug, which we hope will be a better way of treating SLE.
Rogue B Cell Clones In Patients With Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$916,670.00
Summary
Our immune system protects us from disease by producing antibodies. However, 5% of Australians suffer from an autoimmune disease where they produce “auto” antibodies, which attack their own organs. This research will study the cells (termed B cells) responsible for making autoantibodies to determine how they differ from B cells that defend against disease. The goal is to develop therapies that eliminate autoantibody producing B cells from patients while preserving the immune system.
Exploring The Contribution Of Interferon-lambda To Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$833,235.00
Summary
We have found that a novel protein, normally made in response to viral infections, is found in the blood of Lupus patients. This project will determine the cells that make this protein, what in Lupus blood makes these cells produce it and whether it plays a role in the severity of Lupus disease.
Targeting Cytokine Signalling In Systemic Lupus Erythematosus
Funder
National Health and Medical Research Council
Funding Amount
$917,626.00
Summary
Systemic lupus erythematosus is a disease where the immune system attacks normally healthy tissues. The spontaneous overproduction of signalling molecules called interferons in lupus plays an important role in the severity of the disease. We have found that two proteins, named Bcl6 and PLZF, are important in controlling the interferon response in lupus patients. We propose that identifying how these proteins act to control interferon will aid in developing new treatments for lupus.
Interleukin 38: Uncoupling Innate Inflammation From Interferons In Lupus
Funder
National Health and Medical Research Council
Funding Amount
$1,048,669.00
Summary
Systemic lupus erythematosus (SLE) is an incurable autoimmune disease that affects 5 million patients worldwide, mostly young women. Grave multi-organ inflammation and substantial loss of life expectancy render SLE a critical unmet medical need. We found that the immune system protein interleukin 38 disables several signalling pathways essential for SLE progress. We will explore regulation and function of this protein in cells from healthy people and SLE patients and in models of the disease.
How Does Disruption Of Serinc1 Expression Affect Lymphocyte Function And The Development Of Autoimmunity?
Funder
National Health and Medical Research Council
Funding Amount
$681,555.00
Summary
Autoimmune diseases affect up to 8% of the population. We have recently discovered a novel gene mutation in mice that results in increased levels of anti-nuclear antibodies, a hallmark of various autoimmune diseases in humans. The mutated gene, Serinc1, has not been previously implicated in autoimmune disease, but it is important for synthesis of key molecules in immune cells. This research proposal aims to determine how disruption of Serinc1 contributes to the development of autoimmune disease.