The Complementary Effects Of Matrilins And WARP On Chondrogenesis Through TGF-beta Signaling
Funder
National Health and Medical Research Council
Funding Amount
$327,428.00
Summary
Osteoarthritis (OA), characterized by degeneration of articular cartilage matrix structure, is one of the most common types of arthritis. Although it is known that aging is a leading factor, the exact cause of degeneration of articular cartilage is not well understood. In order to aid the discovery of treatments and diagnostic tools for this joint disease, understanding functional and mechanistic properties of cartilage specific proteins, namely matrilins and WARP, is essential.
Elastic Fibre-matrix Interactions Important For Tissue Development, Morphology And Function
Funder
National Health and Medical Research Council
Funding Amount
$376,980.00
Summary
The properties of many tissues are controlled by the type, ratio and organisation of structural proteins laid down into extracellular matrices. Molecular interactions between these different proteins are essential for normal tissue strength, form and function. We are investigating the interactions of protein components of elastic fibres, with structural molecules of the surrounding matrix including collagens, proteoglycans and basement membrane components. At present our knowledge of these inter ....The properties of many tissues are controlled by the type, ratio and organisation of structural proteins laid down into extracellular matrices. Molecular interactions between these different proteins are essential for normal tissue strength, form and function. We are investigating the interactions of protein components of elastic fibres, with structural molecules of the surrounding matrix including collagens, proteoglycans and basement membrane components. At present our knowledge of these interactions is limited even though they are essential for anchorage during stretching of elastic fibres in compliant tissues such as arterial walls, lung and skin. In addition several of the elastic fibre-associated proteins appear to be important in the matrix of non-elastic tissues such as bone and cornea. The project will continue to increase our fundamental understanding of the normal development and function of different connective tissues. This knowledge will, in turn, lead to much greater elucidation of the mechanisms leading to a) loss of tissue function in major disease processes such as atherosclerosis, blood vessel aneurysms, pulmonary emphysema and UV-induced skin damage, and b) developmental abnormalities in congenital disorders such as Marfan syndrome and a variety of corneal dystrophies.Read moreRead less
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
Harnessing The Extracellular Matrix To Fight Obesity-induced Cognitive Impairment
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
The health burden of obesity in Australia is great, but the detrimental impact of obesity on brain function is not yet understood. This research program takes an innovative approach to define how obesity changes non-neuronal brain components that regulate neuroplasticity and protect neurons from damage. Outcomes will define new mechanisms to prevent obesity-induced cognitive impairment and critical knowledge gain leading to novel therapeutic approaches and policy changes to improve health.
The Collagen-rich Matrix As A Driver Of Breast Cancer Progression And Resistance To Therapy
Funder
National Health and Medical Research Council
Funding Amount
$702,230.00
Summary
The extracellular matrix or 'matrix' surrounds all cells and is very important in controlling cell behaviour. In cancer, the matrix is dramatically altered, making cancer more aggressive. We recently developed a new way to study the matrix in breast cancer, and have analysed the matrix at different stages (Early/Mid/Late). We have uncovered exciting new matrix targets associated with more aggressive tumours. This project will validate their potential as therapeutic targets in breast cancer.
Function Of Matrix Proteins Important For Storage And Activation Of TGF And TGF -induced Tissue Remodelling And Repair
Funder
National Health and Medical Research Council
Funding Amount
$690,875.00
Summary
The growth factor TGF is important for tissue development and repair, and in diseases such as pulmonary fibrosis, glomerulonephritis, liver cirrhosis, keloid formation and cancers. This project focuses on 2 important matrix proteins first discovered by Dr Gibson, LTBP-2 and ig-h3, that modulate TGF storage and TGF -induced tissue remodelling . We will use knock out mouse and cell culture models to determine the function of these proteins in tissue development and repair, and in diseases.
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.
Repairing Soft Tissues With Engineered Elastic Biomaterials
Funder
National Health and Medical Research Council
Funding Amount
$2,914,215.00
Summary
There is an urgent medical demand for implantable soft materials that harmonise with surrounding elastic tissue and promote repair. This integrated research program leverages our leading knowledge of human elastic protein. The program’s goals are to develop powerful platform technologies that use this elastic protein, and deliver a new generation of elastic surgical products that can help treat pelvic organ prolapse and repair damaged heart tissue.