Preclinical Assessment Of Gene Therapy For Ventricular Arrhythmia
Funder
National Health and Medical Research Council
Funding Amount
$801,079.00
Summary
Up to 10% of patients are at risk of sudden death following myocardial infarction. Current treatment and preventative initiatives have their limits and are not without risk. In this proposal we will continue to develop an exciting new treatment approach using gene therapy technology. We will attempt to overcome some of the barriers for human application of this technology and pave the way for early phase clinical trials.
A Novel Mechanism For Intestinal Propulsion: Transit Without Neurons Or Pacemakers
Funder
National Health and Medical Research Council
Funding Amount
$256,973.00
Summary
A significant complication of premature births is that the mechanisms that regulate normal intestinal movements have not yet fully developed. We have recently identified a novel pattern of contraction that is seen predominantly in the colon of mice that have not yet developed either the normal nerve circuits that control gut movement and also lack the pacemaker cells that are intrinsic to the muscle coat. This motor pattern appears to be responsible for the movement of gut content during the dev ....A significant complication of premature births is that the mechanisms that regulate normal intestinal movements have not yet fully developed. We have recently identified a novel pattern of contraction that is seen predominantly in the colon of mice that have not yet developed either the normal nerve circuits that control gut movement and also lack the pacemaker cells that are intrinsic to the muscle coat. This motor pattern appears to be responsible for the movement of gut content during the development and maturation of the nerve circuits that regulate this process in more adult animals. However, the mechanisms responsible for this process have not been identified. This project is directed at identifying these mechanismsRead moreRead less
The Role Of Connexin40 In The Pathogenesis Of Atrial Fibrillation Probed By Targeted In Vivo Gene Transfer
Funder
National Health and Medical Research Council
Funding Amount
$529,015.00
Summary
Atrial fibrillation (AF) is a fast and irregular heart rhythm that can predispose sufferers to heart failure and stroke. AF occurs as the result of abnormal electrical conduction in the upper heart chambers. We have found that a protein called Cx40 causes abnormal conduction in heart cells when grown in culture. The aim of this research is to see if AF occurs when Cx40 is increased and prevented when Cx40 is decreased in an AF animal model, potentially defining Cx40 as new therapeutic target.
A Tyrosine Phosphatase That Regulates Adherens Junctions, Cell Migration And The Epithelial-mesenchymal Transition
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Cell-cell adhesion which physically glues cells together to form tissues and organs, also controls processes in development, wound healing and cancer progression. I have identified a novel regulator of cell-cell adhesion that regulates cell migration and cell morphology. Since these events are crucial during metastasis (the spread of cancer) and during wound healing, understanding the function of this novel regulator may provide the basis for new approaches to developing therapeutics. Specifical ....Cell-cell adhesion which physically glues cells together to form tissues and organs, also controls processes in development, wound healing and cancer progression. I have identified a novel regulator of cell-cell adhesion that regulates cell migration and cell morphology. Since these events are crucial during metastasis (the spread of cancer) and during wound healing, understanding the function of this novel regulator may provide the basis for new approaches to developing therapeutics. Specifically, in this proposal I aim to further our understanding of the function of this novel regulator in normal physiology and to elucidate how its functions are regulated.Read moreRead less
Characterisation Of A New Family Of Proteins Involved In Cell Signalling, RNA Metabolism And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$200,880.00
Summary
We have discovered a novel RNA-binding protein (G3BP-2) that is involved in responding to external signals, such as growth factors, at the level of gene expression. Other RNA-binding proteins belonging to the same broad group of proteins are responsible for a host of disease states in mammals including mental retardation, myotonic dystrophy, Huntington?s disease and cancers. Considering the wealth of knowledge accumulated that implicates these proteins to human dysfunction surprisingly few of th ....We have discovered a novel RNA-binding protein (G3BP-2) that is involved in responding to external signals, such as growth factors, at the level of gene expression. Other RNA-binding proteins belonging to the same broad group of proteins are responsible for a host of disease states in mammals including mental retardation, myotonic dystrophy, Huntington?s disease and cancers. Considering the wealth of knowledge accumulated that implicates these proteins to human dysfunction surprisingly few of these RNA-binding proteins have been identified. We have shown that the novel protein discovered in our laboratory is perturbed in cancer and we are interested in characterising its putative role in cancer. The results established in our laboratory so far would indicate that generally, G3BP-2 is expressed in normal tissue and it expression changes in some cancers studied so far. Considering that G3BP-2 lies in a pathway known to be involved in cancer progression it is important to understand what effects the inappropriate expression of G3BP-2 may have on cancer progression and survival. This project is designed to characterise what signals the cell uses to control these proteins and in turn which genes these may effect. In this way we may be able to determine how external signals may effect tumour progression and on what genes this influence is expressed. It would be hoped that this project would increase our understanding of cancer and potentially lead to new diagnostic reagents and therapies in the treatment of cancer.Read moreRead less
The Role Of Connexins In Blood Pressure Regulation: Use Of A Conditional Gene Expression System
Funder
National Health and Medical Research Council
Funding Amount
$583,767.00
Summary
Cell coupling through gap junctions is said to play an important role in regulating blood flow and blood pressure. However data obtained from mice, in which specific gap junctions are deleted, may be compromised by compensatory changes in other junctions. We have validated a new method for rapidly and reversibly altering gap junctions in adult mice with oral sugar. This technique will enable us to directly determine whether interference with cell coupling affects blood flow and blood pressure.
Innovations For Better Cardiovascular Prevention In Primary Care
Funder
National Health and Medical Research Council
Funding Amount
$294,285.00
Summary
The goal of this project is to take a new concept for cardiovascular disease management through the proof-of-concept stage and deliver a novel model for cardiovascular disease management. When proven, the application of this new process for service delivery will provide a low-cost way of closing the gap between guideline recommendations and current management of vascular disease in Australian primary care settings.