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
Deciphering The Overlapping Roles Of SSB1 And SSB2 In The Regulation Of Haematopoiesis And Intestinal Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$996,631.00
Summary
Our work centres on elucidating the role of two newly identified and related single-stranded DNA binding protein (Ssb1 and Ssb2) in development of blood and gut system. When both genes are deleted mice die with 8 days of knockdown due to bone marrow failure and intestinal atrophy. Our double knockout model parallels the consequences of radiation damage on blood and gut system. Toxicity to these systems is a significant hindrance in delivering anti-tumor therapy.
How Replication Stress Activates The Mitotic Telomere DNA Damage Response To Kill Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$486,467.00
Summary
We discovered a novel mechanism linking stress during DNA replication to difficulties with the cell division process, and identified how this turns on DNA damage response signals from the chromosome ends (i.e. “telomeres”). We have further identified that we can exploit this mechanism to kill cancer cells. In this project we will explore this newly discovered mechanism and identify how it can be targeted for therapeutic purposes.
Defective Repair Of Neuronal Activity-induced DNA Double Strand Breaks: A Novel Pathogenic Mechanism For Neurodegeneration In Ataxia-telangiectasia
Funder
National Health and Medical Research Council
Funding Amount
$570,821.00
Summary
The reason for degeneration of the hindbrain in patients with Ataxia-telangiectasia is unknown. Firing of neurons leads to breaks in the DNA that are normally repaired by ATM, the gene defective in Ataxia-telangiectasia, and failure to reset the system likely leads to abnormal gene expression and cell death. Here we use neuronal cell types derived from patient stem cells to elucidate how this novel disease mechanism may cause hindbrain degeneration and to test drugs that can overcome this.
A New Signaling Interface Shapes Cystic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$586,846.00
Summary
This grant investigates the previously uncharacterised association between the INPP5E and AURKA proteins. Both are involved in cell signaling and the development of cystic kidney disease. We will study the nature of this interaction and investigate whether it is possible to ameliorate kidney disease by inhibiting their actions in the developing and adult kidney.
DNA damage response pathways play important roles in preventing the onset of cancer and regulating the clinical response to chemotherapeutics, and some of the relevant proteins have additional functions during normal development. This fellowship will study new a human protein with key roles in the formation of the lung, and its roles in preventing devastating consequences of normal oxidative damage to DNA, as well as additional fundamental mechanisms involved in preventing genome mutations.
Cancer is constantly being suppressed in our bodies by a process that stops damaged cells from growing: 'senescence'. The mechanism that translates the damage stimuli into this state of permanent cell arrest is only partially known. We have identified a protein that appears to drive this restraint. The possibility of manipulating this process to prevent and cure cancer makes it in important target to study.