Modelling TRPV4 Skeletal Disorders Using Human IPSCs
Funder
National Health and Medical Research Council
Funding Amount
$1,171,187.00
Summary
Inherited skeletal disorders are a significant disease burden. Many gene mutations have been defined but we only have limited understanding about how they cause the disease. We will use patient skin cells and new in vitro re-programing technology to induce them to form cartilage cells to produce “disease in a dish” models of human skeletal disorders. These models will allow us to answer questions about how specific mutations cause disease and identify potential therapies
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
The Role Of Tissue Factor In The Regulation Of Extracellular Matrix Remodelling And Angiogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$241,980.00
Summary
The aim of the project is to understand how some blood clotting factors may be involved with the regulation of the extracellullar matrix (the material that exists between cells) and angiogenesis (new blood vessel formation). New blood vessel growth occurs in a wide variety of situations including: healing of a flesh wound, the healing phase following a heart attack, development of the eye disease associated with sugar diabetes, in and around a cancerous growth, in the uterus during the normal me ....The aim of the project is to understand how some blood clotting factors may be involved with the regulation of the extracellullar matrix (the material that exists between cells) and angiogenesis (new blood vessel formation). New blood vessel growth occurs in a wide variety of situations including: healing of a flesh wound, the healing phase following a heart attack, development of the eye disease associated with sugar diabetes, in and around a cancerous growth, in the uterus during the normal menstrual cycle, and for the normal growth and development of the placenta and a new baby. The processes by which these new blood vessels form and the factors contributing to the maintenance of their structure are incompletely understood. However, it is known that the interaction of cells and the surrounding extracellular matrix is critical for normal cell function and in particular for new blood vessel formation. Studies in this project will seek to define a relationship between some of the factors which regulate blood clotting, and those that regulate turnover of the extracellular matrix and new blood vessel formation. In particular, how blood clotting factors may be invovled in the regulation of the extracellular matrix will be studied in a rapidly developing tissue, the mouse placenta. The role of blood clotting factors in regulation of new blood vessel formation into an artificial avascular tissue will also be examined. These studies will employ some of the new genetic techniques to understand new roles for proteins which have been traditionally thought to act in only one way. This research has the potential to provide new insights into how blood vessels are formed and are subsequently maintained. This increased understanding will provide the knowledge required for the development of new therapeutic strategies to correct the process when it goes wrong, is unwanted or underdeveloped in human disease.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.
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.