The Influence Of NF-KB In The Development Of Autoimmunity And Cancer In Fas/FasL Mutant Mice
Funder
National Health and Medical Research Council
Funding Amount
$596,925.00
Summary
Apoptotic cell death is an essential process in the human body, it removes useless and dangerous cells, preventing autoimmune disease and cancer. Apoptosis is activated when the surface receptor Fas is stimulated by its ligand, FasL, but defective signalling causes disease associated with deregulated NF-?B activation. We will investigate how faulty FasL-induced apoptosis cooperates with deregulated NF-kB activation or defective Aire (immunological tolerance orchestrator) results in autoimmunity.
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.
How Deletional And Non-Deletional Tolerance Mechanisms Integrate To Prevent Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$509,944.00
Summary
The body produces millions of immune cells every day to fight infection. Some of these immune cells are defective and dangerous because they can cause autoimmune diseases, like Type I diabetes and multiple sclerosis. To defuse this risk, such immune cells are either caused to die or are inactivated to prevent autoimmunity. We propose to investigate how the processes of immune cell death and inactivation work in health and disease so we may harness these mechanisms to cure autoimmunity.
How Does NF-kB2 Regulate Thymic Selection To Prevent Organ-specific Autoimmune Disease?
Funder
National Health and Medical Research Council
Funding Amount
$787,600.00
Summary
Autoimmune diseases like type 1 diabetes and thyroiditis arise from defects that cause the immune system to confuse self and non-self. Normally, this distinction is programmed in the thymus. We recently identified the gene that causes a form of autoimmune disease. We also made an important discovery about how the thymus gland regulates self-non-self discrimination. We will build on these two discoveries to gain a precise understanding of how the immune system normally avoids autoimmune disease.
Dendritic Cells And CCAAT/enhancer Binding Protein-delta (CEBP?) In Neuroinflammation And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$576,538.00
Summary
This projects aims to develop new treatments by finding the cells and chemicals that naturally stop inflammation in the central nervous system in diseases like MS. It also aims to test new treatments by delivering them to where this inflammation takes place. This targeted delivery should mean fewer side effects because the rest of the body is not exposed to the treatment. Hopefully this will reduce the impact of these diseases on the community, and reduce side effects for the patient.
Evolution Of Adaptive Immunity To Gluten In Coeliac Disease.
Funder
National Health and Medical Research Council
Funding Amount
$472,034.00
Summary
Coeliac disease affects 1 in 100 Australians and can cause significant health problems. Under-diagnosis and a difficult, costly treatment (lifelong gluten free diet) are serious clinical issues. The feasibility of simpler diagnostics and therapies in children and adults for coeliac disease depends on whether children and adults react in the same way to gluten. This proposal seeks to determine whether the immune response to gluten changes over time and establish the feasibility of peptide-based a ....Coeliac disease affects 1 in 100 Australians and can cause significant health problems. Under-diagnosis and a difficult, costly treatment (lifelong gluten free diet) are serious clinical issues. The feasibility of simpler diagnostics and therapies in children and adults for coeliac disease depends on whether children and adults react in the same way to gluten. This proposal seeks to determine whether the immune response to gluten changes over time and establish the feasibility of peptide-based applications.Read moreRead less
Inflammatory diseases, such as autoimmune diseases, result from an overactive immune system. A new therapy that is currently under trial is the use of special blood cells, called Treg cells, whose function is to suppress unwanted immune responses. This application evaluates the efficacy and safety of such treatments.
Investigating The Aetiopathogenic Role Of Autoantibodies Against The M1 Muscarinic Acetylcholine Receptor In Patients With First Episode Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$830,986.00
Summary
Previously we have found that a proportion of patients with schizophrenia have elevated levels of antibodies that target one of the neurotransmitter receptors, the M1 muscarinic acetylcholine receptor, and that those patients who have the highest levels of antibodies tend to have more severe manifestations of some of the symptoms of schizophrenia. In this project, we will try to confirm this relationship, and also investigate further how this antibodies might be able to worsen specific symptoms.
Pathogenesis Of A New Mouse Model Of Ankylosing Spondylitis
Funder
National Health and Medical Research Council
Funding Amount
$682,820.00
Summary
Ankylosing spondylitis and Crohn's disease are autoimmune inflammatory diseases which cause long-term pain and deformity of joints, spine and bowel. Using a new mouse model of both diseases, we will study cells and processes involved in the initiation of disease, in order to discover new targets for prevention and treatment. The work will have importance for design of new therapies for human inflammatory spine and bowel diseases.
The Role Of NF-?B Transcription Factor RelA In Regulatory T Cell Homeostasis And Function
Funder
National Health and Medical Research Council
Funding Amount
$637,114.00
Summary
Treg cells constitute an immune regulatory cell population that is essential for the prevention of fatal autoimmunity; however, they also limit immunity against cancer. We have discovered that the factor RelA is of critical importance for Treg development and function. We now aim to illuminate the functions of RelA in detail. Understanding the molecules that impact on Treg cell biology is critical to harness their potential for clinical intervention such as treatment of autoimmunity and cancer.