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.
Bridging The Gap In Kidney Transplantation Using Pigs As Donors
Funder
National Health and Medical Research Council
Funding Amount
$1,452,341.00
Summary
Chronic kidney failure results in patients suffering significant morbidity and mortality ultimately requiring life-supporting dialysis. Kidney transplantation and lifelong immunosuppression are the only treatment, but (i) is limited by the shortage of human donors and (ii) carries risks associated with these anti-rejection drugs. This project aims to solve both problems by using humanized pigs as donors combined with a novel approach to inducing acceptance of the transplanted kidneys.
Using Porcine Embryonic Stem Cells To Advance Xenotransplantation And Human Stem Cell Research To The Clinic.
Funder
National Health and Medical Research Council
Summary
We have developed a new method for isolating embryonic stem cells (ESCs) and have used this to isolate porcine ESCs. The aims of the present study are to use this breakthrough to advance xenotransplantation as well as human stem cell research
Investigating Tumour Biology Using Regulated RNAi In Cells And Mice
Funder
National Health and Medical Research Council
Funding Amount
$305,915.00
Summary
Inhibiting gene expression using the recently discovered process known as RNA interference (RNAi) can be used as an experimental tool to analyse specific genes, in cells and genetically engineered animal models of human disease. I propose to use RNAi to mimic human cancer gene mutations in mouse cancer models, and aim to discover novel tumour suppressor genes. A further aim is to validate potential drug targets in cancer by using RNAi to inhibit specific genes in established mouse tumours.
Eradicating Leukaemic Stem Cells By Targeting The Arginine Methyltransferase PRMT5
Funder
National Health and Medical Research Council
Funding Amount
$770,950.00
Summary
Acute leukemia is a devastating cancer arising from primitive cells in the bone marrow called stem cells. We have identified a protein (PRMT5) that is highly expressed in leukemia stem cells. Our preliminary experiments suggest that blocking the function of this protein with a novel drug can stop the growth of these cells. This project will use a variety of mouse models of acute leukemia to determine how PRMT5 keeps stem cells alive and whether this drug will be a valuable new treatment.
A Novel Cardiac Inotropic Mechanism That Provides Functional Benefit
Funder
National Health and Medical Research Council
Funding Amount
$413,936.00
Summary
Patients with heart failure are often treated with an inotropic agent to increase the force of the heart's contraction and thus improve quality of life for these patients. Most inotropic agents have deleterious effects that limit their usefullness. Mice that have increased alpha1-A receptor expression in their hearts have heightened contactility that is not associated with hypertrophy or arrhythmias. We will use microarray, and si-RNA delivery and signalling studies to identify the mechanism.
The Role Of Liver Fructose-1,6-phosphatase (FBPase) In Body Weight Regulation
Funder
National Health and Medical Research Council
Funding Amount
$494,718.00
Summary
We have shown that fructose-1,6-bisphosphatase (FBPase), an enzyme important in producing sugar from the liver and one that is connected to Type 2 diabetes, does not cause an increase in sugar production when there is more of the enzyme in mouse livers. It does, however, lower both body weight and the amount of food the mice consume. We therefore hypothesise that liver FBPase is important in controlling body weight in humans and our project aims to find out exactly how and why this happens.