The Role Of Hypoxia In The Developmental Programming Of The Kidney
Funder
National Health and Medical Research Council
Funding Amount
$651,276.00
Summary
We aim to understand how inadequate oxygen supply to the fetus during pregnancy can affect development of the kidney. Many babies do not get enough oxygen whilst developing in the womb. This can be due to a poorly formed placenta or the mother smoking. This can interfere with normal growth and formation of the kidney. Our knowledge may help babies get the best start to life.
Involvement Of The Asciz Gene In Kidney Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$591,128.00
Summary
Congenital abnormalities of the kidney and urinary tract (CAKUT) affect more than 1/500 children. Urogenital development is primarily controlled by a small number of genes that regulate the timing and position of kidney formation. In this application we describe a novel gene involved in this process, establish where it acts, how it regulates gene expression and whether mutations in it cause CAKUT.
Understanding The Developmental Basis Of Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$622,655.00
Summary
Kidney disease is a considerable burden on the health system and much of it derives from events that occur during organ development. In this grant I will investigate why human nephron number varies between people, how renal cysts form and what genes are mutated in patients with congenital kidney malformations.
Generation Of Renal Cells From Human Embryonic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$281,805.00
Summary
This proposal will gather evidence to show that human embryonic stem cells are capable of forming specific cell types of the embryonic human kidney. Once this is established, methods for the maintenance and directed differentiation of these cells to cell types of the mature kidney will be identified and improved. The results obtained will provide a base for future exploration of the possibility that human embryonic stem cell derived cells can be used to treat damaged kidneys.
Regenerating The Kidney Using An Understanding Of Normal Development
Funder
National Health and Medical Research Council
Funding Amount
$951,005.00
Summary
In Australia, chronic kidney disease costs >$1 billion per annum, however treatment options for kidney failure have not changed for >50 years. Dialysis reduces quality of life and lifespan while only 1 in 4 patients receives a transplant. Using our understanding of normal kidney formation, this study will generate kidney tissue from human stem cells to better understand inherited kidney diseases and develop novel regenerative therapies for the treatment of end stage kidney disease.
Directed Differentiation Of Human Embryonic Stem Cells To Kidney Progenitors
Funder
National Health and Medical Research Council
Funding Amount
$652,600.00
Summary
In Australia, 11.3% of deaths are associated with chronic kidney disease, costing the health system >$1 billion per annum. No stem cell exists in the adult kidney that can replace damaged kidney filters. We have preliminary results suggesting we may be able to make kidney stem cells from embryonic stem cells or induced pluripotent cells. In this project, we will optimise the conditions required and test the ability of these cells to form new kidney structures.
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
In this proposal, we will use genome sequencing to identify novel mutations in patients presenting with kidney disease. We will also generate stem cell lines from these patients and their unaffected relatives in order to model the disease. Finally, we will create animal models of the same mutations. As a result, we hope to better understand the causes of the disease and begin to develop new treatment options.
The Role Of Crim1, A Novel TGFb Superfamily Modulator, In Early Vertebrate Patterning, Vascular And Renal Development.
Funder
National Health and Medical Research Council
Funding Amount
$501,300.00
Summary
The transforming growth factor (TGF) beta superfamily is a large group of secreted growth factors who play many different roles in normal development of tissues such as the brain, skeleton, heart, kidney, eyes, teeth and limbs. One of the groups within the superfamily, the bone morphogenetic proteins (BMPs), are being used in clinical trials to assist in regrowing bones after fracture. These molecules are also of interest for clinical reasons as growth factors within this family can also be dele ....The transforming growth factor (TGF) beta superfamily is a large group of secreted growth factors who play many different roles in normal development of tissues such as the brain, skeleton, heart, kidney, eyes, teeth and limbs. One of the groups within the superfamily, the bone morphogenetic proteins (BMPs), are being used in clinical trials to assist in regrowing bones after fracture. These molecules are also of interest for clinical reasons as growth factors within this family can also be deleterious, with their overexpression leading to conditions such as renal fibrosis and cataract. The activity of these growth factors is regulated by many other proteins, including protein antagonists which bind and inactivate them. It is therefore possible that by understanding these antagonists, we can find new ways of altering TGF beta superfamily activity. We have previously identified a novel protein, Crim1, which we have now shown can bind to TGF superfamily members and can reduce their secretion. We believe that Crim1 plays a role in the patterning of the central nervous system, the development of the blood vessels and the kidneys by regulating the TGFbeta superfamily. In this grant we will be investigating what the effect of disruption to Crim1 is on these organ systems and working out which members of the TGFbeta superfamily it is affecting to cause these effects. To do this, we will knock out the gene in zebrafish and characterise the defects found in a mouse line in which the gene has been disrupted. This may be important in developing new ways of activating or inactiviating these growth factors in a number of clinical conditions.Read moreRead less