Cell Biology Of Stress Fractures: Activation Of Remodelling At Sites Of Non-union
Funder
National Health and Medical Research Council
Funding Amount
$493,817.00
Summary
Stress fractures are debilitating injuries. We characterised a model of stress fractures in rat ulnae, learning that they heal by activated remodelling, that key genes are expressed in a temporal pattern, and that part of the fracture remains un-healed, similar to many clinical cases. Now, we will examine cell localisation of important genes necessary for remodelling, and test the efficacy of different growth factors to activate a healing response in the non-healed section of the fracture.
The Role Of Dermal Mast Cells In Limiting The Pathology Associated With Chronic Low-dose UVB Irradiation Of The Skin.
Funder
National Health and Medical Research Council
Funding Amount
$513,945.00
Summary
Australians are subject to high levels of sun exposure , that consequently can lead to skin damage and skin cancer. The specific aims of our reseearch are to investigate the role of skin mast cells in the limitation of skin alterations associated with chronic low-dose ultraviolet B exposure. Understanding the innate mechanisms that protect against excessive skin damage and cancer might aid the development of better treatment modalities in the future.
Early Events In Arteriolar Remodeling: Adaptation To Prolonged Vasoconstriction
Funder
National Health and Medical Research Council
Funding Amount
$415,750.00
Summary
Small arteries, while acutely responding to their environment with changes in diameter to regulate local blood flow and pressure, also undergo structural adaptation or remodelling. These events occur over a range of time-frames and involve both non-genetically and genetically regulated events. Thus a contractile event, while initially decreasing vessel diameter, also activates longer time frame processes which can span from rearrangment of cellular junctions-contacts to overt structural changes ....Small arteries, while acutely responding to their environment with changes in diameter to regulate local blood flow and pressure, also undergo structural adaptation or remodelling. These events occur over a range of time-frames and involve both non-genetically and genetically regulated events. Thus a contractile event, while initially decreasing vessel diameter, also activates longer time frame processes which can span from rearrangment of cellular junctions-contacts to overt structural changes within the vessel wall (for example thickening of the muscle layer). These adaptive processes may enable the forces of contraction to be maintained without continued energy expenditure and damage to the vessel per se. However, they can also contribute to long-term alterations in the control of blood pressure and perhaps contribute to states of hypertension as well as other common vascular diseases. For these studies we will use arterioles, isolated by microsurgical techniques, together with sophisticated computer and video-based approaches. These techniques allow arterioles to be studied under controlled conditions and relevant biochemical measurements performed. We will also use a cell model where cultured cells will be studied after defined periods of mechanical stimulation (for example stretch). Cells will be probed using a novel microscopic technique (atomic force microscopy) which enables the cell membrane to be studied with respect to changes in composition as well as physical characteristics (for example stiffness). The studies are relevant to our understanding of the normal adaptive processes occurring within blood vessels to control blood flow and pressure. The studies are also of direct relevance to our understanding of common vascular disease states including hypertension, complications of diabetes and chronic inflammatory disorders.Read moreRead less
Periodontal Mesenchymal Stem Cells For Periodontal Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$358,000.00
Summary
Dental diseases affecting the gums (periodontal disease) are extremely prevalent in our society. The effects of periodontal disease can be particularly severe as loss of support for the teeth leads to loose teeth and severely compromised masticatory function. If left untreated, the associated pain and loss of function may necessitate extraction of the teeth. We have recently identified cells residing in the periodontal ligament which may be adult stem cells. This project will further characteriz ....Dental diseases affecting the gums (periodontal disease) are extremely prevalent in our society. The effects of periodontal disease can be particularly severe as loss of support for the teeth leads to loose teeth and severely compromised masticatory function. If left untreated, the associated pain and loss of function may necessitate extraction of the teeth. We have recently identified cells residing in the periodontal ligament which may be adult stem cells. This project will further characterize these cells and explore whether they can be used to restore periodontal tissues damaged by periodontal disease.Read moreRead less
Atrial Electrical Remodeling Due To Chronic Stretch: Defining The Substrate For Atrial Fibrillation
Funder
National Health and Medical Research Council
Funding Amount
$428,250.00
Summary
Background: Cardiac failure is a common heart disorder in which the pumping function of the heart is significantly weakened. Mitral regurgitation is a common condition where there is a leakage of blood from the left ventricle (lower heart chamber) back into the left atrium (upper heart chamber) during normal cardiac contraction. This puts a strain on the heart and may cause heart failure. Atrial septal defect is a common form of congenital heart disease which may not be diagnosed until adulthood ....Background: Cardiac failure is a common heart disorder in which the pumping function of the heart is significantly weakened. Mitral regurgitation is a common condition where there is a leakage of blood from the left ventricle (lower heart chamber) back into the left atrium (upper heart chamber) during normal cardiac contraction. This puts a strain on the heart and may cause heart failure. Atrial septal defect is a common form of congenital heart disease which may not be diagnosed until adulthood. There are several forms but the basic problem is leakage of blood from the left atrium into the right atrium .This also puts a strain on the heart and can cause heart failure. All 3 conditions are associated with a significantly increased risk of atrial fibrillation (AF). This abnormal fast irregular cardiac rhythm makes the pumping of the heart inefficient. People with AF may feel short of breath, tired, or develop palpitations. AF is an important cause of stroke and premature death and is the most common heart rhythm disturbance occurring in upto 10% of the over 70 age group. Even after repair of the leaky valve or atrial septal defect there is still a high risk of developing this rhythm. Purpose of the study: This study will try to understand why patients with these conditions are at risk of developing atrial fibrillation, and why this risk might persist after surgical correction when this is possible (mitral regurgitation and atrial septal defect). The study will utilise sophisticated new mapping techniques to gain original insights into the mechanism of this very common and as yet poorly understood heart rhythm disturbance. The study has the potential to determine the cause of atrial fibrillation in these patient groups and as such represent a quantum advance in our understanding of he mechanism of atrial fibrillation. It would be expected to form a foundation on which development of curative and preventative approaches may be based.Read moreRead less
Restoration Of The Nigrostriatal Pathway In The Parkinsonian Brain
Funder
National Health and Medical Research Council
Funding Amount
$299,431.00
Summary
Many obstacles exist for cell transplantation in Parkinson's disease; namely poor restoration of the host brain circuitry due to incorrect graft placement. This results in incomplete motor function and unwanted side effects. Through iterative studies we endeavor to restore this circuitry by placing grafts in the appropriate location and promoting their survival and growth-integrations. This will require: optimizing the donor tissue and exposure of the graft to growth stimulating factors.
Wnt Signaling In Dopaminergic Neuronal Connectivity
Funder
National Health and Medical Research Council
Funding Amount
$564,721.00
Summary
A major obstacle in repairing the injured or diseased brain is inducing axons (nerve cell processes) to make the appropriate connections. This is especially true following cell replacement therapy (CRT) in Parkinson's disease (PD). We will examine the processes inducing axons in the dopamine pathways to grow. We hypothesize that Wnt signaling plays and important role and that therapeutic introduction of Wnt is required to repair the dopamine pathways following CRT in PD.