Determinant Spreading And The Role Of The MHC Class II Region In Systemic And Organ-specific Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$140,570.00
Summary
Autoimmune diseases are among the most important group of disorders affecting the adult population. In these diseases the immune system damages organs and tissues producing widespread pathology (systemic autoimmunity such as Lupus erythematosus) or localised disease (organ-specific autoimmunity such as insulin dependent diabetes). We understand very little about how and why the immune system attacks the body's own tissues. This study examines how antibodies and T lymphocytes are formed against c ....Autoimmune diseases are among the most important group of disorders affecting the adult population. In these diseases the immune system damages organs and tissues producing widespread pathology (systemic autoimmunity such as Lupus erythematosus) or localised disease (organ-specific autoimmunity such as insulin dependent diabetes). We understand very little about how and why the immune system attacks the body's own tissues. This study examines how antibodies and T lymphocytes are formed against components located inside cells of the body. The study involves genetically modifying mice by introducing key human genes which influence the development of autoimmunity. In this way the role of these human genes can be examined experimentally without having to work exclusively on patients. We also hope that these mice might be important in creating new models of celiac disease and insulin dependent diabetes. The proposed experiments should tell us how these genes contribute to the development of autoimmune disease. This understanding could be relevant devising treatments and interventions to prevent autoimmune diseases.Read moreRead less
Cortical Spreading Depressions: Effects On Intracellular Ca2+ Concentration And Mechanisms Of Propagation
Funder
National Health and Medical Research Council
Funding Amount
$185,604.00
Summary
Human neuropathologies such as migraine, stroke, focal epilepsy and head injury all appear to involve an event called cortical spreading depression (CSD). This is characterised by a transient loss of excitability of cells that slowly spreads from a site of initiation out across the cortical surface. In normal brain tissue CSDs do not kill cells but in tissue with less than optimal energy supply CSDs do kill cells. This project is designed to understand the mechanisms contributing to CSD-induced ....Human neuropathologies such as migraine, stroke, focal epilepsy and head injury all appear to involve an event called cortical spreading depression (CSD). This is characterised by a transient loss of excitability of cells that slowly spreads from a site of initiation out across the cortical surface. In normal brain tissue CSDs do not kill cells but in tissue with less than optimal energy supply CSDs do kill cells. This project is designed to understand the mechanisms contributing to CSD-induced cell death. It is widely accepted that a high intracellular concentration of calcium ions is lethal to a cell. Thus, the proposed experiments are expected to show that a single episode of CSD in normal brain tissue induces only small changes in the intracellular calcium ion concentration but if repeated episodes of CSD occur, and if they take place in tissue with a compromised energy supply, then the calcium concentration rises to detrimental levels. Little is known about the mechanisms which underlie the propagation of CSD and therefore experiments will also be undertaken to investigate whether release of a messenger into the extracellular space is important or if there is a role for release of calcium from intracellular stores.Read moreRead less
Antibiotic Resistance And Multiple Antibiotic Resistance In Human Commensal Escherichia Coli In Australia
Funder
National Health and Medical Research Council
Funding Amount
$509,202.00
Summary
Antibiotic resistance, particularly resistance to all or nearly all of the antibiotics available for treatment is now very common and impacts heavily on the treatment of bacterial infections. This project will track resistance genes in reservoirs where antibiotic resistance genes may be present in high concentrations as these are a likely source of the resistance genes in disease-causing bacteria. One such reservoir, the bacteria in the intestines of healthy humans will be examined.
Initiation And Diversification Of Systemic Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$200,749.00
Summary
One of the striking findings in autoimmune diseases such as systemic lupus erythematosus and Sjogren's syndrome is the presence in the blood of autoantibodies reacting with certain proteins or autoantigens. The best known autoantigens are termed La and Ro and are important diagnostic markers in these two common conditions. It appears that the immune response starts against Ro and then spreads to La over time, a process known as epitope spreading. There is emerging evidence in Sjogren's syndrome ....One of the striking findings in autoimmune diseases such as systemic lupus erythematosus and Sjogren's syndrome is the presence in the blood of autoantibodies reacting with certain proteins or autoantigens. The best known autoantigens are termed La and Ro and are important diagnostic markers in these two common conditions. It appears that the immune response starts against Ro and then spreads to La over time, a process known as epitope spreading. There is emerging evidence in Sjogren's syndrome that the severity of this condition is related to the degree of epitope spreading to Ro and La, which in turn is controlled by the genetic background of the individual. We therefore wish to study the initiation of the autoimmune response to Ro and the factors which influence spreading or diversification to La, using a mouse model of La-Ro autoimmunity which we have developed. In addition, we shall investigate the potential role of a recently identified gene in a large group of patients with Sjogren's syndrome. We believe this gene may control the epitope spreading and expression of disease. The role of other molecules called chaperones (which bind to Ro) and complement (involved in clearing dead cells which may trigger autoimmunity) will also be studied. The ultimate goal of the work is to develop ways of blocking the epitope spreading which should ameliorate the disase and patients' symtpoms.Read moreRead less