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Understanding The Causes Of Childhood Congenital Anomalies Of The Kidney And Urinary Tract
Funder
National Health and Medical Research Council
Funding Amount
$609,748.00
Summary
Congenital anomalies of the kidney and urinary tract (CAKUT) is a common cause of renal failure in children. The majority of patients with CAKUT do not know the underlying cause of their renal anomalies. In this proposal we will characterise the developmental events that are perturbed in three mouse models of CAKUT and identify the causal gene responsible in each mouse model. We will translate this information to the clinic by screening patients with CAKUT for mutations in these newly identified ....Congenital anomalies of the kidney and urinary tract (CAKUT) is a common cause of renal failure in children. The majority of patients with CAKUT do not know the underlying cause of their renal anomalies. In this proposal we will characterise the developmental events that are perturbed in three mouse models of CAKUT and identify the causal gene responsible in each mouse model. We will translate this information to the clinic by screening patients with CAKUT for mutations in these newly identified genes.Read moreRead less
Human Podocyte Depletion, Glomerular Hypertrophy And Glomerulosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$601,490.00
Summary
Many kidney diseases commence with injury to glomeruli (kidney filters) which leads to glomerular scarring and loss. There is strong evidence from animal studies that a specific glomerular cell type (the podocyte) is central to this process of glomerular injury. In this study, we will analyse the relationships between podocyte depletion and glomerular scarring in human kidneys from 5 racial groups (white and African Americans, white and Aboriginal Australians, Senegalese Africans).
Birth Weight, Adult Weight And Podocyte Depletion.
Funder
National Health and Medical Research Council
Funding Amount
$796,252.00
Summary
A major role of our kidneys is to filter our blood. A key cell type in our kidney filters is an octopus-shaped cell known as the podocyte. If we are not born with enough podocytes, or if the filters grow too large after birth due for example to excessive weight gain, the podocytes cannot adequately filter the blood, and this can lead to kidney disease. We will measure podocyte endowment at birth, and assess the effects of weight gain and loss after birth on podocyte features and kidney health.
Novel Approaches To The Prevention And Treatment Of Chronic Heart Disease And Its Co-morbid Complications
Funder
National Health and Medical Research Council
Funding Amount
$5,793,580.00
Summary
Cardiovascular disease (CVD) and its associated additional disorders constitute major public health problems, especially given the rapidly ageing population which is increasingly affected by obesity and diabetes. This Program will explore novel therapies for the treatment of CVD and associated diseases, particularly focussing on chronic kidney disease, translating preliminary laboratory-based findings into clinical trials and then clinical and epidemiological findings into practice and policy.
Exercise As Medicine For Heart Failure: A Novel Intervention To Improve Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$665,585.00
Summary
Heart failure (HF) is a common, debilitating and expensive disease; prognosis remains poorer than for the most cancers. 30,000 Australians are diagnosed every year and 300,000 live with the HF, at an annual cost of ~$1Billion. Exercise training is effective therapy in HF, because it reverses many of the problems that contribute to the reduced lifespan and impaired quality of life of patients with HF. We will test an exciting new type of exercise that promising greater benefit, at lower risk.
Characterization Of Novel Regulators Of Erythropoiesis
Funder
National Health and Medical Research Council
Funding Amount
$437,545.00
Summary
Mature red and white blood cells develop from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for epo to stimulate them to become mature fu ....Mature red and white blood cells develop from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for epo to stimulate them to become mature functional cells. We have identified six molecules which interact with Lyn in red blood cells. We have shown that amolecule called HS1 is important for epo function in individual red blood cells and now we plan to investigate its functions in whole animals, including mice that lack the HS1 gene. We have also shown that a molecule called Trip1 is important for red blood cell development. Interestingly, this molecule also interacts with the thyroid hormone receptor and can influence the effects of epo and thyroid hormone on red blood cell development. The interplay between these two hormones will be looked at in more detail both at the cell and whole animal levels in normal mice and those lacking the thyroid hormone receptor gene. The third Lyn binding molecule we isolated is a novel gene-we have named it ankyrin repeat protein in line with the molecules it is related to. This gene is expressed in red blood cells and we aim to investigate what role it plays in the development of these cells. The fourth gene is also novel and is closely related to another called AFAP-110, which can exert effects on the structure of a cell. Its role in red blood cell structure will also be investigated. Finally, the last two molecule we have identified are both novel and are unrelated to any other known proteins. As above, the effects of these two molecules on red blood cell development will be investigated.Read moreRead less
Antigen Selection In The MHC-restricted Cellular Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$175,570.00
Summary
The body's white cells eliminate microorganisms through the actions of immune lymphocytes and other cells which conspire to kill and neutralise these unwanted guests. When microorganisms hide inside the cells of the body they are still detected by a set of T lymphocytes which have specific receptors for scrutinising the surface of cells for any changes which might signal an intracellular infection. The immune system is ever vigilant in its search for signs of infection which are generally appare ....The body's white cells eliminate microorganisms through the actions of immune lymphocytes and other cells which conspire to kill and neutralise these unwanted guests. When microorganisms hide inside the cells of the body they are still detected by a set of T lymphocytes which have specific receptors for scrutinising the surface of cells for any changes which might signal an intracellular infection. The immune system is ever vigilant in its search for signs of infection which are generally apparent when molecules called antigens are released by microorganisms and captured by the body's cells. This activates lymphocytes resulting in an immune response capable of eliminating the microorganisms. Scrutiny of the body's cells by lymphocytes occurs continuously even when there is no infection present in the body. Following infection of a cell, microbial antigens reveal the infection by their appearance on the cell surface where they are detected by the immune system's lymphocytes. This occurs through a mechanism called antigen presentation. During antigen presentation the proteins inside the cell, including those of any invading microorganism, are first degraded into shorter molecules called peptides. This event is called antigen processing. A fraction of the peptides created by antigen processing are captured by specialised receptors present on all cells. These receptors are called HLA or histocompatibility molecules. This project examines the molecular events which mediate the capture of peptide antigens by HLA molecules. The main focus is on those peptide antigens which elicit killer T cell responses by the immune system. A knowledge of how these peptides are selected for presentation and how they are captured and carried to the cell surface is fundamental to understanding immune responses to microorganisms, tumours, allergens, transplants and self tissues as in autoimmunity. Therefore the study is of great general relevance.Read moreRead less