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.
Developmental Programming: Mechanisms And Interventions
Funder
National Health and Medical Research Council
Funding Amount
$705,501.00
Summary
Disturbances during pregnancy can impact on developmental processes and result in increased risk of disease in later life. This project will examine the impact of perturbations such as maternal stress or alcohol consumption on the development of the placenta and fetal kidney. By gaining an understanding of how these organs are affected by prenatal insults, we are likely to be able to develop more effective intervention strategies to ensure all babies receive a healthy start to life.
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.
Single Nephron GFR And Tubuloglomerular Feedback Before And After Birth.
Funder
National Health and Medical Research Council
Funding Amount
$402,428.00
Summary
In this project we want to study the forces responsible for the filtration of plasma by the kidney during development. This process is the first step in urine production. It is important to understand kidney function because abnormalities in kidney function can result in high blood pressure and chronic renal disease (requiring dialysis or transplant) in later life. It is reported that up to 40% of the population is salt sensitive i.e. their blood pressure increases when they are on a high salt d ....In this project we want to study the forces responsible for the filtration of plasma by the kidney during development. This process is the first step in urine production. It is important to understand kidney function because abnormalities in kidney function can result in high blood pressure and chronic renal disease (requiring dialysis or transplant) in later life. It is reported that up to 40% of the population is salt sensitive i.e. their blood pressure increases when they are on a high salt diet. The cause of this salt sensitivity is unknown but we believe that it could be due to abnormalities in kidney function during fetal life. Alterations in function occuring during development can have life long effects through a process called fetal programming.Read moreRead less
Novel Therapy For Enhancing Organ Maturation In Pre-term Babies
Funder
National Health and Medical Research Council
Funding Amount
$694,323.00
Summary
This project is developing a factor to enhance organ maturation and repair that may provide a new therapy for premature babies and fetuses with birth defects. This exciting new finding allows for the development of treatments of underdeveloped organs, in particular the lungs of premature and growth restricted babies. We are also trialing this factor in unborn babies with defects to the kidneys and lungs of which there is currently no cure.
I am a physiologist working to understand how disturbances during pregnancy can alter fetal development and increase the risk of developing adult onset diseases such as cardiovascular disease, renal disease and diabetes. In particular I am interested in how alterations in kidney development may play a crucial role in disease development.
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
Exploring The Physiological, Morphological And Molecular Bases Of Renal Developmental Programming.
Funder
National Health and Medical Research Council
Funding Amount
$422,264.00
Summary
Suboptimal fetal and neonatal development increases our risk of developing a range of diseases in adulthood. The concept that deleterious events during development can influence adult health is termed 'developmental programming'. Obtaining A Healthy Start to Life is a priority research goal of the Australian Government. The kidneys are particularly susceptible to developmental programming. This is in part because the functional units (nephrons) of the kidneys are all formed before birth in human ....Suboptimal fetal and neonatal development increases our risk of developing a range of diseases in adulthood. The concept that deleterious events during development can influence adult health is termed 'developmental programming'. Obtaining A Healthy Start to Life is a priority research goal of the Australian Government. The kidneys are particularly susceptible to developmental programming. This is in part because the functional units (nephrons) of the kidneys are all formed before birth in humans. Thus, if fetal development is suboptimal, babies are at risk of being born with a permanent nephron deficit, with functional and disease consequences. We have shown in male rats that the offspring of a maternal low protein diet have fewer nephrons and lower blood pressure than rats fed a normal diet. These rats display a striking sensitivity in adulthood to the feeding of a high salt diet. We will define the physiological and morphological bases of this sensitivity, and repeat these studies in females, as increasing evidence shows significant sex differences in developmental programming. Defining the molecular mechanisms of developmental programming is the greatest challenge for researchers in the field. We have recently completed the most comprehensive analysis to date of gene expression in the developing mouse kidney, and have shown for the first time that the mouse programmes kidney development. We will use the new techniques of genomics and bioinformatics to study the molecular mechanisms of kidney programming. This mechanistic data will provide an excellent hypothesis engine for future studies on the specific roles of these molecular pathways in developmental programming in all mammalian species.Read moreRead less
Altered Renal Development Programs Adult Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$607,289.00
Summary
If a mother suffers an adverse condition during pregnancy - such as high blood pressure - the development of the baby is altered, putting it at increased risk of cardiovascular disease in adulthood. Our study in rabbits examine the role that changes to nerves in the kidney play in the development of high blood pressure later in life and whether it can be prevented via short-term anti-hypertensive treatment in the postnatal period .