E-CADHERIN AS A KEY MOLECULE IN RENAL EPITHELIAL-MESENCHYMAL TRANSITION AND FIBROSIS
Funder
National Health and Medical Research Council
Funding Amount
$318,267.00
Summary
Chronic kidney disease (CKD) is a major cause of death and disability in the Australian population. Current treatments for CKD are non-specific and frequently ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or transplantation to remain alive. Every year more than 1700 Australians require kidney replacement therapy for this reason and many more die of kidney failure or its complications. Kidney fibrosis is the final common result of diverse CK ....Chronic kidney disease (CKD) is a major cause of death and disability in the Australian population. Current treatments for CKD are non-specific and frequently ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or transplantation to remain alive. Every year more than 1700 Australians require kidney replacement therapy for this reason and many more die of kidney failure or its complications. Kidney fibrosis is the final common result of diverse CKD. This project proposes to investigate EMT, a key event in the development of renal fibrosis, whereby kidney cells are converted to fibrogenic cells. The project focuses on matrix enzymes (metalloproteinases) and E-cadherin (a molecule which is involved in adherence of kidney cells to one another, but which we think may actually be involved in the causation of EMT). This focus is novel, and could provide new understanding about the process of EMT in renal fibrosis, knowledge relevant to all diseases characterised by eventual loss of organ function due to fibrosis. It will identify new targets for therapy aimed at preventing fibrotic diseases of all types.Read moreRead less
AMP-activated Protein Kinase (AMPK) In Acute Renal Failure
Funder
National Health and Medical Research Council
Funding Amount
$401,523.00
Summary
Acute renal failure is a common complication of any severe illness. Generally, it is the lack of blood flow, or food that leads to this problem. People who are ill are unable to provide adequate blood flow to their kidneys, so the kidneys become diseased and fail to function. This can be fatal. There are, however, mechanisms in the kidney that are designed to avoid this shortage of energy. The aim of these studies is to find out what these protective mechanisms usually do in the kidney, and unde ....Acute renal failure is a common complication of any severe illness. Generally, it is the lack of blood flow, or food that leads to this problem. People who are ill are unable to provide adequate blood flow to their kidneys, so the kidneys become diseased and fail to function. This can be fatal. There are, however, mechanisms in the kidney that are designed to avoid this shortage of energy. The aim of these studies is to find out what these protective mechanisms usually do in the kidney, and understand why they are not more active. We hope to find ways to switch them on earleir, using drugs, so as to protect the kidneys from injury.Read moreRead less
Investigating The Use Of Bone Marrow Transplantation To Study And Treat Polycystic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$349,250.00
Summary
Polycystic kidney disease (PKD) is a common genetic condition that causes fluid filled cysts to form in the kidney. In many cases, these cysts lead to kidney failure. Once the kidneys fail irreversibly, the only treatments available are dialysis and kidney transplantation. Dialysis to remove waste products from the blood is time consuming and does not completely replace all functions of the kidney. Kidney transplantation is limited by the availability of donor organs. At present, there are no re ....Polycystic kidney disease (PKD) is a common genetic condition that causes fluid filled cysts to form in the kidney. In many cases, these cysts lead to kidney failure. Once the kidneys fail irreversibly, the only treatments available are dialysis and kidney transplantation. Dialysis to remove waste products from the blood is time consuming and does not completely replace all functions of the kidney. Kidney transplantation is limited by the availability of donor organs. At present, there are no reliable ways to prevent the onset or slow the progression of PKD. The kidney consists of a complex system of tubules and ducts. PKD causes the cells that make up these tubules and ducts to grow uncontrollably and form cysts. We are using mice to study how mutations affect the mechanisms that control cell growth in the kidney and cause PKD. Bone marrow cells can move to the kidney and repair it after damage. We will test if bone marrow cells carrying a PKD mutation can cause PKD when transplanted into a healthy mouse. This will help us learn how mutations cause PKD in humans. We will also see if normal bone marrow can prevent disease when transplanted into a mutant mouse that spontaneously develops PKD. This experiment may lay the basis for a way to treat human PKD.Read moreRead less
Function Of The Lysophospholipid Receptor Family In Neuronal Stem Cells And Their Progenitors.
Funder
National Health and Medical Research Council
Funding Amount
$380,723.00
Summary
Stem cells have the potential to give rise to a vast array of differentiated cells. Neuronal stem cells (NSC) can differentiate into progenitor cells which can themselves differentiate into cells of the nervous system: neurons and macroglial cells (astrocytes, oligodendrocytes, Schwann cells). This in turn can assist in the treatment of degenerative diseases such as multiple sclerosis, Parkinson's disease, motoneuron desease etc. Our project aims to study the effects on NSC and their progenitor ....Stem cells have the potential to give rise to a vast array of differentiated cells. Neuronal stem cells (NSC) can differentiate into progenitor cells which can themselves differentiate into cells of the nervous system: neurons and macroglial cells (astrocytes, oligodendrocytes, Schwann cells). This in turn can assist in the treatment of degenerative diseases such as multiple sclerosis, Parkinson's disease, motoneuron desease etc. Our project aims to study the effects on NSC and their progenitor cells of the lysophospholipids lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P), bioactive molecules known to play an essential role in the nervous system during development and inflammation. Our project aims to understand the mechanisms of action of these molecules in NSC maintenance, proliferation, differentiation and migration. By understanding how these molecules are able to regulate NSC biology will provide new avenues in the development of tools necessary for stem cell therapy.Read moreRead less
Regulation Of The Drosophila C-Myc Homologue In Stem Cell Growth And Division.
Funder
National Health and Medical Research Council
Funding Amount
$613,397.00
Summary
The mechanisms controlling stem cell growth and division require elucidation if we are to use stem cells in regenerative medicine and find cancer treatments. Due to experimental limitations such mechanisms are largely unknown in humans. We aim to use the vinegar fly as a model system to understand the importance of microenvironment to cancer gene control in stem cells. We will identify the secreted signals, from the neighbouring cells, required to control cancer initiation in stem cells.