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.
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
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
RENAL VASCULAR HYPERTROPHY AND REMODELLING IN SHR: SYMPATHETIC NERVOUS SYSTEM AND IMPLICATIONS FOR HYPERTENSION
Funder
National Health and Medical Research Council
Funding Amount
$191,561.00
Summary
High blood pressure (hypertension) remains a major health problem for Australians. One in six Australians suffer from hypertension, with consequent increased risk of stroke and heart attack. Anti-hypertensive treatments are available, but must usually be taken for the rest of the patient's life and the cost to the taxpayer of anti-hypertensive drugs is greater than for any other health problem. Prevention of high blood pressure depends on identifying the initial cause - but we still do not know ....High blood pressure (hypertension) remains a major health problem for Australians. One in six Australians suffer from hypertension, with consequent increased risk of stroke and heart attack. Anti-hypertensive treatments are available, but must usually be taken for the rest of the patient's life and the cost to the taxpayer of anti-hypertensive drugs is greater than for any other health problem. Prevention of high blood pressure depends on identifying the initial cause - but we still do not know the cause in over 90% of hypertensive people. This project will study whether overactivity of the nerves to the blood vessels of the kidney might be the cause. There is evidence for this in humans, and in a strain of rats which develops high blood pressure (the spontaneously hypertensive rat). Our experiments will study these rats to see whether nerves affect the structure and function of the blood vessels of the kidney in ways that lead to increased blood pressure.Read moreRead less
The study of growth factors essential in normal kidney and lung development allows for the advancement of innovative therapies to promote postnatal growth and repair. A revolutionary new therapy for treatment of growth restricted fetuses and premature babies is being developed through the administration of colony stimulating factor (CSF-1), a growth factor important for fetal growth during pregnancy. We have evidence that CSF-1 therapy can promote lungs to continue development and maturation aft ....The study of growth factors essential in normal kidney and lung development allows for the advancement of innovative therapies to promote postnatal growth and repair. A revolutionary new therapy for treatment of growth restricted fetuses and premature babies is being developed through the administration of colony stimulating factor (CSF-1), a growth factor important for fetal growth during pregnancy. We have evidence that CSF-1 therapy can promote lungs to continue development and maturation after birth.Read moreRead less
Mechanisms Of Infection Triggered Renal Vasculitis
Funder
National Health and Medical Research Council
Funding Amount
$413,900.00
Summary
Kidney disease, including glomerulonephritis, is an important cause of ill-health in Australia. Some forms of kidney inflammation are linked to infection, but we don�t understand why. This project explores products from bacteria, particularly S.aureus, to work out how bacterial infection affects a form of kidney inflammation - ANCA-associated glomerulonephritis. It will establish how infection related signals activate local and immune cells, and define links between infection and the disease.
Kidney failure is a devastating consequence of diabetes mellitus. Evidence exists that increased amounts of glucose are filtered by the kidney and then together with salt is reaborbed, in patients with diabetes. The increased glucose and salt reabsorption is considered to trigger cellular damage leading to renal failure. The studies will determine if reducing glucose and salt resportion by the kidney protects against the development of renal failure in models of diabetic renal disease.