IgA nephropathy is one of the most common causes of kidney failure in Australia and around the world, but there are currently no specific treatments proven to prevent kidney failure. The SIGNAL trial, jointly led by Australian and Chinese researchers, will bring together leading experts from around the world to reliably ascertain the effects of steroid therapy in this condition, and could potentially prevent many people from developing kidney failure in the future.
Fc Alpha RI: Ligand Interaction And Membrane Organisation.
Funder
National Health and Medical Research Council
Funding Amount
$497,640.00
Summary
Antibodies tag invading viruses or bacteria thus marking them as foreign and targeting them for destruction by the immune system. In man the most prevelant antibody is IgA and this antibody provides protection from infecton in the blood and in the fluids at the surface of the lungs, gut and urinogenital tract. Once tagged by antibody the invading bacteria or antigen can be recogniseed white blood cells. These workhorses of the immune system use special molecules called Fc receptors on their surf ....Antibodies tag invading viruses or bacteria thus marking them as foreign and targeting them for destruction by the immune system. In man the most prevelant antibody is IgA and this antibody provides protection from infecton in the blood and in the fluids at the surface of the lungs, gut and urinogenital tract. Once tagged by antibody the invading bacteria or antigen can be recogniseed white blood cells. These workhorses of the immune system use special molecules called Fc receptors on their surface to recognise antibody tags. The receptor for IgA tags is called the Fc alpha receptor. This receptor is essential for the normal IgA-mediated protection against infection. However in a common kidney disease IgA tags accumulate in the glomerulus of the kidney stimulating white blood cells to attack and damage the kidney. This study will explain how the Fc alpha receptor recognises IgA antibody tags. It will investigate how the presentation of different forms of the receptor and different types of IgA antibody tags contributes to immunity to infection. For example one form of the receptor has a fat molecule joined to its end. We believe this may affect where the Fc alpha recptor goes to in the white blood cell membrane and whether it can activate the white blood cell to fight the invading microorganism.Read moreRead less
Targeting Epigenetic Pathways That Lead To Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$989,948.00
Summary
Glucose remains the major cause of complications in diabetes with prior episodes of high glucose having long lasting effects on blood vessels leading to heart attacks, kidney disease and blindness. We have identified an enzyme Set7 which plays a key role in promoting glucose induced injury. By validating this target using drug and molecular approaches we will strengthen the rationale to develop potent inhibitors of this enzyme in order to reduce the major burden of diabetes, its complications.
Role Of The Podocyte In Diabetic Nephropathy: Structural, Functional, Molecular And Interventional Studies
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Kidney disease is a major cause of disability and premature death in the Australian population. In disease the kidney's ability to filter out impurities and toxins in blood is impaired as a consequence of excessive cell growth and scar tissue formation. Studies from our group indicate that a highly specialised cell within the kidney's filtering apparatus becomes altered early in the course of diabetes. In the setting of diabetes, this cell, called the podocyte, stretches and begins forming scar ....Kidney disease is a major cause of disability and premature death in the Australian population. In disease the kidney's ability to filter out impurities and toxins in blood is impaired as a consequence of excessive cell growth and scar tissue formation. Studies from our group indicate that a highly specialised cell within the kidney's filtering apparatus becomes altered early in the course of diabetes. In the setting of diabetes, this cell, called the podocyte, stretches and begins forming scar tissue. In addition, it no longer maintains its barrier function and starts to leak protein. The proposed studies will explore the mechanisms that lead to these diabetes-induced changes in the podocyte. In addition, strategies for reversing these changes will also be explored in detail with the aim of providing new treatments for diabetic kidney disease.Read moreRead less
Fibrosis is a major mechanism driving chronic disease. A specific pathologic process (TGF/Smad signalling) plays an important role in scarring of the kidney and the heart; but our understanding of this process is limited. Our exciting new data has identified a chemical modification of a component of this scarring pathway (acetylation of Smad3), and this project seeks to determine whether this modification plays a pivotal role in regulating tissue scarring.