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Innovative Stem Cell-based Strategies To Establish Immune Tolerance And Tissue Repair
Funder
National Health and Medical Research Council
Funding Amount
$5,554,618.00
Summary
Diseases such as autoimmune gastritis, multiple sclerosis and diabetes arise because a rogue immune system has turned inwards to attack our organs. The organ destruction follows from recognition by the immune system of specific molecules in these organs. These autoimmune diseases are incurable and controlled mainly by long-term administration of substances that suppress the immune system, often with serious side-effects. A rational approach is to render the rogue immune system harmless by removi ....Diseases such as autoimmune gastritis, multiple sclerosis and diabetes arise because a rogue immune system has turned inwards to attack our organs. The organ destruction follows from recognition by the immune system of specific molecules in these organs. These autoimmune diseases are incurable and controlled mainly by long-term administration of substances that suppress the immune system, often with serious side-effects. A rational approach is to render the rogue immune system harmless by removing the cells that recognize these particular molecules. This can be achieved by a Trojan horse approach in which the molecules are delivered to the immune system such that that the immune cells that recognize them are removed. To deliver these molecules to the immune system we will genetically engineer bone marrow stem cells, or embryonic stem cells that generate these stem cells, because they are precursors of mature immune cells. Rejection of organ transplants arise in a similar way and also require long-term immunosuppression. A similar approach can therefore be taken to promote acceptance of foreign organ grafts. In the aged, we will combine these approaches with rejuvenation of the immune system by blockade of sex steroid production and-or by creation of a new immune organ.Read moreRead less
The Role Of Susceptibility Genes And Microbiota In Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$303,924.00
Summary
Utilising my background in Immunology I will investigate whether specific genetic mutations can create a susceptibility for dysregulation of the flora and immune system within the gut, thus predisposing an individual to inflammatory bowel diseases (ulcerative colitis and Crohn's disease) as well as non-intestinal inflammatory conditions. These diseases are becoming an increasingly prevalent and serious health burden in Australia. We aim to use this knowledge in order to design specific treatment ....Utilising my background in Immunology I will investigate whether specific genetic mutations can create a susceptibility for dysregulation of the flora and immune system within the gut, thus predisposing an individual to inflammatory bowel diseases (ulcerative colitis and Crohn's disease) as well as non-intestinal inflammatory conditions. These diseases are becoming an increasingly prevalent and serious health burden in Australia. We aim to use this knowledge in order to design specific treatments for these diseases.Read moreRead less
The Molecular Determinants Of Immunological Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$473,477.00
Summary
Autoimmune diseases, such as type I diabetes and multiple sclerosis, are debilitating disorders that impose a massive toll on wellbeing in Australia and worldwide. This fellowship will support research aimed at determining the genes and mechanisms that control autoimmunity. New technologies will be brought to bear to track immune cells throughout their development, maturity and malfunction in disease settings. We aim to uncover new therapeutic targets to prevent and reverse autoimmune disease.
The Control Of Autoimmunity Originating From Somatically Hypermutated B Cells
Funder
National Health and Medical Research Council
Funding Amount
$530,337.00
Summary
Our immune systems are capable of producing long-lived antibodies that can last a lifetime. Sometimes, this powerful process can however become abnormal and result in autoimmune diseases such as lupus. We have recently developed the first experimental mouse model that allows researchers to study this process in great detail. This funding will extend our initial observations by identifying the exact mechanisms by which important regulators of autoimmune disease act.
Prevention Of Autoimmune Diabetes By Immune Tolerance To Proinsulin
Funder
National Health and Medical Research Council
Funding Amount
$504,597.00
Summary
In type 1 diabetes, insulin is the first target of the immune system. Strategies to prevent the immune system targeting insulin in mice early in the disease process work, but it is not clear if such strategies would be effective if applied late. This is important because preventive therapies for human type 1 diabetes are currently feasible only late in the disease process. We aim to address this by removing T cells specific for insulin at different stages of the disease.
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.