Oxidation Of Arterial Extracellular Matrix By Myeloperoxidase-derived Oxidants
Funder
National Health and Medical Research Council
Funding Amount
$183,266.00
Summary
It is well established that changes occur in the composition and nature of the extracellular matrix present in the artery wall during the development of atherosclerosis. The changes that occur in this matrix affect both the mechanical and physical properties of the arterial wall (e.g. its ability to cope with the high pressures genrated by the pumping of blood from the heart) and the adhesion of cells. It is well established that certain key cell types do not adhere well, or grow properly, on al ....It is well established that changes occur in the composition and nature of the extracellular matrix present in the artery wall during the development of atherosclerosis. The changes that occur in this matrix affect both the mechanical and physical properties of the arterial wall (e.g. its ability to cope with the high pressures genrated by the pumping of blood from the heart) and the adhesion of cells. It is well established that certain key cell types do not adhere well, or grow properly, on altered or damaged matrix and this can result in either the loss of key cell types from the artery wall (e.g. loss of endothelial cells) and - or the proliferation and invasion of cells from other sources (e.g. smooth muscle cell invasion into the intimal space). There is circumstantial evidence that some of these changes occur via the formation of oxidants by the heme enzyme myeloperoxidase which is released from activated white cells. In this study we will employ recently developed analytical techniques to examine the nature of the alterations that are present in atherosclerotic plaques in comparison to normal human artery samples, and investigate the mechanisms by which such alterations arise. We will seek evidence for, or against, the involvement of myeloperoxidase-derived oxidants in the observed changes using specific markers which we have developed for the presence of such damage. This information will allow the rational design of strategies to interfere with the progression of atherosclerosis, which is the major killer of Australians.Read moreRead less
Defective Cell Migration As A Mechanism Of Dysregulated Asthmatic Airway Repair
Funder
National Health and Medical Research Council
Funding Amount
$616,712.00
Summary
Injury of the airway epithelium (cells lining the airways) is normally repaired by a process involving the deposition of specific proteins by the airway epithelial cells, promoting them to attach and migrate to cover the injury. These cells appear to be abnormal in asthmatics, in that they fail to repair. By studying specimens from healthy, allergic and asthmatic children we will determine the factors that influence the ability of these cells to repond to an injury in a normal manner specificall ....Injury of the airway epithelium (cells lining the airways) is normally repaired by a process involving the deposition of specific proteins by the airway epithelial cells, promoting them to attach and migrate to cover the injury. These cells appear to be abnormal in asthmatics, in that they fail to repair. By studying specimens from healthy, allergic and asthmatic children we will determine the factors that influence the ability of these cells to repond to an injury in a normal manner specifically through their ability to migrate.Read moreRead less
I am a basic scientist with an interest in the cellular biology of the ovary, and the roles of the matrix between cells of the ovary in controlling fertility and hormone synthesis.
Bridging The Gap Between Cartilage Biology And Osteoarthritis Risk Prediction
Funder
National Health and Medical Research Council
Funding Amount
$512,256.00
Summary
Osteoarthritis is a painful and debilitating cartilage disease affecting just under 1 in 10 Australians and costs the Australian economy roughly $12 billion per year. This project will develop computational models of cartilage with the ability to incorporate genetic and environmental risk factors into a predictive model of cartilage disease.
The Role Of Force-sensing Ion Channels In Melanoma Migration
Funder
National Health and Medical Research Council
Funding Amount
$553,848.00
Summary
Metastasis of melanoma cells away from the primary tumour site carries a very poor patient prognosis.This research aims to characterise a novel signalling pathway that can regulate the migration (movement) of melanoma cells. This signalling pathway depends on force-sensing platforms that can rapidly convert physical inputs from the environment into an electrical signal within the cell. We are working to understand how these force-sensors function.
Evaluation Of Tissue Engineered Decellularised Biphasic Constructs For Periodontal Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$578,031.00
Summary
This project aims to regenerate the tissues lost as a result of gum disease. This will be done using scaffolds that replicate the complex structure of periodontal tissues.The scaffolds will be loaded with cells and allowed to mature before the cellular component is removed. The resultant construct is then inserted back into periodontal defects where it will be repopulated by host cells. This approach has the potential to be developed into an off-the-shelf clinical treatment.
Improving Cancer Diagnostic Imaging And Drug Delivery By Breaking Down Extracellular Matrix Barriers
Funder
National Health and Medical Research Council
Funding Amount
$748,152.00
Summary
Solid tumours are stiffer than normal tissues. This stiffness is caused by over-production of non-cellular components known as extracellular matrix (ECM). ECM creates a barrier that restricts drug access in tumours. New methods to overcome tumour stiffness are crucial to improve drug delivery. We will study the use of a new compound to degrade tumour ECM to improve anti-cancer drug delivery. Our compound will be useful in treatment-resistant solid tumours such as breast and liver cancers.