Transgenic Expression Of The EWS-WT1 Fusion Protein,inducing The Development Of Tumour That Replicates The Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$112,976.00
Summary
A genetic translocation encoding the EWS-WT1 fusion protein is found desmoplastic small round cell tumours. Our aim is to examine the effect of this protein in inducing tumour growth in tissue cell lines. A virus will then be used to introduce the genetic translocation into mice to examine the effect of this protein on tumour growth in a mammal, thereby serving as a 'solid tumour model' to try and identify therapeutic targets.
Harnessing RNA Interference In Gene Therapy Vectors For ?-thalassaemia
Funder
National Health and Medical Research Council
Funding Amount
$719,188.00
Summary
There is an urgent need to develop safe and effective treatments for ?-thalassaemia. We anticipate that ?-globin-specific RNAi sequences will synergise with ?-globin transgene expression to achieve balanced ?-/?-globin ratio in a clinical setting. Given that one of the major issues with current gene therapy vectors is achieving high levels of expression, we believe this will be a more effective gene therapy strategy than ?-globin transgene expression alone.
The Brain As A Therapeutic Target For Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$923,432.00
Summary
In heart failure there is a large increase in sympathetic nerve activity to the heart that leads to damage to the heart and sudden death. We have shown that lesion of the area postrema, a brain nucleus that senses hormones in the blood, reduces nerve activity to the heart and, importantly, improves cardiac function. We aim to translate these findings into a treatment that can be used clinically, which our findings compellingly indicate should improve cardiac function in heart failure
Analysis And Manipulation Of The Genome-wide Integration Signatures Of Gamma-retroviral And Lentiviral Vectors In Human Haematopoietic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$612,154.00
Summary
Gene therapy has been successful in treating several diseases involving the bone marrow, but has been associated with the development of leukaemia in a number of patients. The cause has been tracked to the gene transfer technology used and associated damage to the genetic blueprint of treated cells. In this study we plan to use high-throughput genetic analysis to better understand the nature of this damage and to develop strategies to improve the safety of the gene repair process.
Developing Bone Marrow Transplant And Novel Therapeutic Vectors To Treat Friedreich Ataxia
Funder
National Health and Medical Research Council
Funding Amount
$598,163.00
Summary
We aim to develop effective therapies for the neuromuscular disease Friedreich ataxia (FRDA). The neurodegeneration inherent to FRDA slowly robs a person of the ability to move freely and care for themselves. It needs life-long medical support and there is no cure. FRDA lowers frataxin, a critical mitochondrial protein. Evidence indicates increasing frataxin can be beneficial. Using disease models, we will determine if increasing frataxin via bone marrow transplant or gene therapy improves FRDA.
Reversal Of Diabetes In Pigs Using Liver-directed Gene Therapy
Funder
National Health and Medical Research Council
Funding Amount
$573,807.00
Summary
Type I diabetes mellitus is caused by the autoimmune destruction of the beta cells of the pancreas that secrete insulin. We have shown that we can cure diabetes in spontaneously diabetic mice by delivery of the insulin gene to the liver using a non-pathogenic viral delivery system. The study aims to repeat this work in pigs which have similar physiology to humans. If successful this would be proof-of-principle that we could theoretically control blood glucose levels in humans.
Correction Of Diabetes In An Autoimmune Model Using Insulin-secreting Liver Cells.
Funder
National Health and Medical Research Council
Funding Amount
$472,500.00
Summary
Type I diabetes mellitus is caused by the autoimmune destruction of the beta cells of the pancreas that secrete insulin. The problems of the chronic complications of diabetes and the lack of donor tissue for transplantation, could theoretically be overcome by engineering from the patient's own cells, an artificial beta cell, i. e. a non-islet cell capable of synthesising, storing and secreting mature insulin in response to metabolic stimuli, such as glucose. The ultimate goal of this technology ....Type I diabetes mellitus is caused by the autoimmune destruction of the beta cells of the pancreas that secrete insulin. The problems of the chronic complications of diabetes and the lack of donor tissue for transplantation, could theoretically be overcome by engineering from the patient's own cells, an artificial beta cell, i. e. a non-islet cell capable of synthesising, storing and secreting mature insulin in response to metabolic stimuli, such as glucose. The ultimate goal of this technology is to deliver the insulin gene directly to a patient's own liver cells which would regulate insulin secretion in response to glucose and other substances that stimulate insulin secretion, controlling blood glucose without the need for immunosuppression. To accomplish this it must be possible to deliver the insulin gene efficiently to primary liver cells (cells derived from an animal's or human's body). Results from our laboratory using a non-pathogenic viral delivery system indicate that we can reverse diabetes in chemically induced diabetic rats by expression of insulin and a beta cell transcription factor NeuroD. The aim of this study is to repeat this in an auto-immune model of diabetes the nonobese diabetic mouse, which mimicks very closely the development of diabetes in humans. We will determine if we can reverse diabetes in these animals and determine if their response to glucose is normal over an extended period of time, with no attack by the factors of the immune system that stimulate the development of diabetes in man. The results from this research proposal should result in the delivery of the insulin gene to large numbers of primary liver cells that will then synthesise, store and secrete insulin in response to glucose. These cells would control blood glucose levels in patients without the need for immunosuppression.Read moreRead less
In Australia, chronic kidney disease costs >$1 billion per annum and can only be treated by dialysis or transplantation. Your kidney function depends upon what happened during your development as all the functional units of the kidney are made prior to birth from a stem cell population that then disappears. We have found a way to recreate these stem cells from adult cells. In this project, we will optimise this process and investigate whether regenerated stem cells can repair an adult kidney.
Modelling The Loss Of NF1 Heterozygosity In Congenital Pseudarthrosis Of The Tibia (CPT).
Funder
National Health and Medical Research Council
Funding Amount
$482,978.00
Summary
Congenital pseudarthrosis of the tibia or CPT is a dibilitating orthopaedic condition that affects children. Healing of a CPT is poor and, even with modern surgical techniques, amputation is a frequent outcome. As a group experienced in animal models of bone healing, we are well positioned to develop advanced genetic models of CPT in mice. With a better understanding of the underlying processes in CPT we will be able to develop treatments for this severe childhood condition.