Coupling The Mechanical, Signalling And Transcriptional Mechanisms That Initiate Pathogenesis Of Cerebral Cavernous Malformation
Funder
National Health and Medical Research Council
Funding Amount
$1,228,364.00
Summary
Cerebral cavernous malformations (CCMs) are thin walled, vascular malformations in the brain found in 1/200-250 individuals. They can cause migraine, neurological deficits or stroke. This disease can be inherited due to damaging mutations in any of three CCM genes. The project will investigate the molecular control of CCM pathogenesis in animal models. We aim to uncover the molecular cause of these vascular malformations and in doing so identify new therapeutic strategies.
Biomarkers For Risk And Outcomes Of Type 2 Diabetes: A Discovery And Validation Approach In Australian And Chinese Subjects
Funder
National Health and Medical Research Council
Funding Amount
$599,489.00
Summary
The aim is to make better outcomes for people with Type 2 diabetes in Australia and China, by exploring various tests to improve prediction of diabetes progression, complication risk and treatment response. The team has data and samples from the Fenofibrate Intervention and Event Lowering in Diabetes Trial and from the Shanghai Diabetes Study. This approach is very time and cost-effective. We will also study animal models to understand mechanisms of diabetes damage, and test new treatments.
Regulator Of G Protein Signalling-5 Loss And Gain Of Function In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$625,428.00
Summary
Cancer and cardiovascular diseases are amongst the largest causes of morbidity and mortality in Western populations. We have identified a molecule, called Regulator of G protein signalling 5 (RGS5), which is involved in vessel remodelling in both diseases. This molecule is a prime candidate for drug development. We will study the precise role of RGS5 in sophisticated preclinical models which will create future opportunities for urgent therapy.
Calcification of the arteries is a ubiquitous finding in patients with end stage renal failure. It is often mirrored by disturbed bone metabolism. Increasing evidence suggests a close relationship between bone and vascular health. This study aims to determine the role of calciprotein particles as a mediator of calcification in bones and arteries. Translating these findings to renal patients will ultimately contribute to providing a scientific basis for developing treatment for these patients.
The Role Of Platelet Derived Growth Factor Receptor Alpha (Pdgfra) In Coronary Vascular Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$666,840.00
Summary
The coronary vessels supply blood to heart muscle. Blockage of coronary vessels causes heart attacks which are the leading cause of death in the Western world. A recent focus for heart attack researchers is to re-establish the blood supply to the injured area by creating new blood vessels. We have found a new gene involved in creating coronary blood vessels. We will characterize how this gene is involved in this process. Knowledge about this gene may foster new treatments for heart attack.
Role For Sphingosine Kinase-1 In Endothelial Progenitor Cell Survival And Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$294,205.00
Summary
Lay description: Collectively, diseases of the vascular system contribute immensely to the burden of health care in Australia. Notably, abnormal blood vessel formation and function (angiogenesis) has been identified as a major cause or contributor to the vascular complications associated with inflammation, cancer, rheumatoid arthritis and diabetes. Endothelial cells are one of the principle cells of blood vessels forming a barrier between the blood and tissues. This project aims to understand th ....Lay description: Collectively, diseases of the vascular system contribute immensely to the burden of health care in Australia. Notably, abnormal blood vessel formation and function (angiogenesis) has been identified as a major cause or contributor to the vascular complications associated with inflammation, cancer, rheumatoid arthritis and diabetes. Endothelial cells are one of the principle cells of blood vessels forming a barrier between the blood and tissues. This project aims to understand the process whereby mature endothelial cells are formed and how replacement of damaged endothelial cells is normally achieved. Stem cell therapy is considered the new frontier for the treatment of many diseases. Understanding how endothelial progenitor cells differentiate to mature endothelial cells and the signals which operate inside the cell may allow therapeutic manipulation of key target moecules in order to limit or control inflammation, tumourigenesis, rheumatoid arthritis and diabetic retinopathy. Our results suggest that one target maybe the enzyme sphingosine kinase.Read moreRead less
Characterisation And Regulation Of Chloride Channels In Cardiac And Skeletal Sarcoplasmic Reticulum In Mammals
Funder
National Health and Medical Research Council
Funding Amount
$381,856.00
Summary
An understanding of the operation of ion channels in cell membranes is fundamental to our knowledge of the function of muscles under normal conditions and in pathological states that modify cell function, e.g. myotonia and cardiac failure. Ion channels control the flow of currents and the transport of substances which ultimately determine whether cells live or die, and hence whether cell pathologies are expressed as muscle failure, as when hypoxia causes tissue damage to the heart, or as severe ....An understanding of the operation of ion channels in cell membranes is fundamental to our knowledge of the function of muscles under normal conditions and in pathological states that modify cell function, e.g. myotonia and cardiac failure. Ion channels control the flow of currents and the transport of substances which ultimately determine whether cells live or die, and hence whether cell pathologies are expressed as muscle failure, as when hypoxia causes tissue damage to the heart, or as severe arrythmia or cardiac arrest. The objective is to understand channel involvement in the mechanisms underlying the function of cardiac and skeletal muscle. We believe that by mimicking the factors that occur in pathological conditions we can understand how ion channels are altered and controlled, and find ways of reversing harmful alterations, thereby reversing cell damage and failure of vital muscle function.Drugs will be used to modify the 'gating' of the channels. By comparing the effects of different drugs, we hope to determine the important features of the mechanisms that control the gating of the channels, making them more or less sensitive to different influences, especially those that occur in pathological states. The study has great application to the study of other pathologies, e.g. cystic fibrosis, severe diarrhoea, paralysis and chronic fatigue. The pharmacological emphasis offers the fundamental science needed to design novel and specific drugs to combat the many serious pathologies related to ion channel effects. Aside from its importance to basic science and to immediate issues of health, the study offers considerable economic gains, both through improved public health and through development of pharmaceuticals.Read moreRead less
Viral Therapy For Skeletal Muscle Alpha-actin Disease And Discovery Of Novel Neuromuscular Disease Genes And Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$324,028.00
Summary
This research project is the next logical step towards treating patients with skeletal muscle actin disease - using viral delivery of normal actin genes in animal models of actin disease. Another arm of this project is to investigate the genetics and mechanisms causing two very different groups of muscle disorders in the Australian population: devastating muscle weakness in the foetal akinesias and enhanced muscle strength and bulk in individuals with strongman syndromes.
Preclinical Testing Of 3 Cysteine-related Drugs For Reducing Dystropathology In The Mdx Mouse Model Of Duchenne Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$378,564.00
Summary
Duchenne muscular dystrophy (DMD) is devastating disease that affects young boys. We propose testing 3 cysteine related drugs which show promise in ameliorating the severity of the disease. The drugs are of particular interest because they are relatively inexpensive, can be taken orally, have few side effects and are already approved for human use. These drugs will tested in an animal model of DMD to test their efficacy.
The Role Of The Systemic Milieu In Preventing Motor Unit Remodelling And Loss During Ageing
Funder
National Health and Medical Research Council
Summary
Motor unit remodeling and loss contributes to the decline in muscle mass, strength and quality of life in our aging population. Recent data shows that exposing aged mice to 'blood-borne factors' from the circulation of a young mouse can reverse the age-associated deficits in motor unit structure and function. A better understanding of the factors controlling these anti-aging effects will be vital for finding new compounds to reverse the aging process and improve quality of life.