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Research Topic : SHEAR-STRESS
Scheme : NHMRC Project Grants
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  • Funded Activity

    Investigation Of The Role Of Phosphoinositide 3-kinase In Regulating The Haemostatic Function Of Platelets

    Funder
    National Health and Medical Research Council
    Funding Amount
    $554,190.00
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    Funded Activity

    Investigation Of The Role Of GPIb-V-IX In Mediating Platelet Adhesion Under Flow

    Funder
    National Health and Medical Research Council
    Funding Amount
    $188,844.00
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    Funded Activity

    Investigation Of The Structural Domains Of GPIb-V-IX Regulating Platelet Adhesion And Signal Transduction

    Funder
    National Health and Medical Research Council
    Funding Amount
    $390,785.00
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    Funded Activity

    Investigating Biomechanical Platelet Activation Mechanisms

    Funder
    National Health and Medical Research Council
    Funding Amount
    $514,280.00
    Summary
    Seminal findings within our laboratory have demonstrated that disturbances of blood flow are an important trigger for blood clot formation, promoting heart attacks and stroke. Our studies have demonstrated that specialised blood cells, termed platelets, respond rapidly to local changes in blood flow in diseased blood vessels. In the present proposal we aim to identify the mechanisms by which platelets sense and respond to blood flow disturbances with the aim of identifying new approaches to prev .... Seminal findings within our laboratory have demonstrated that disturbances of blood flow are an important trigger for blood clot formation, promoting heart attacks and stroke. Our studies have demonstrated that specialised blood cells, termed platelets, respond rapidly to local changes in blood flow in diseased blood vessels. In the present proposal we aim to identify the mechanisms by which platelets sense and respond to blood flow disturbances with the aim of identifying new approaches to prevent disease-causing blood clots.
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    Funded Activity

    The Coronary Vascular Bed, Shear Stress, Endothelial Signalling And Myocyte Electrophysiology

    Funder
    National Health and Medical Research Council
    Funding Amount
    $133,774.00
    Summary
    Physiologic control muscle performance includes a little understood signal from the walls of blood vessels stimulated by pressure and flow which effect muscle function. How this signal operates is controversial. We have developed a model which enables the evaluation of such signalling where changes in flow in the circumflex coronary artery induce easily measured local changes in electrophysiology which are confined to the territory of the circumflex coronary artery and which can be compared with .... Physiologic control muscle performance includes a little understood signal from the walls of blood vessels stimulated by pressure and flow which effect muscle function. How this signal operates is controversial. We have developed a model which enables the evaluation of such signalling where changes in flow in the circumflex coronary artery induce easily measured local changes in electrophysiology which are confined to the territory of the circumflex coronary artery and which can be compared with control values from the left anterior descending coronary artery territory. We propose to use this stable model to evaluate the origin, the transmission agent and the mechanism by which it alters the action potential duration.
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    Funded Activity

    Defining The Roles Of Platelet Protease-activated Receptors In Thrombosis

    Funder
    National Health and Medical Research Council
    Funding Amount
    $330,690.00
    Summary
    Inappropriate blood clot formation is the cause of most heart attacks and some strokes. Platelets are the blood cells responsible for such clots. We are interested in the signals which control platelet incorporation into clots because drugs that interfere with this may be effective at inhibiting unwanted clot formation. Our studies determining the importance of platelet signals will provide strong clues to the likely effectiveness of blocking such signals as anti-clotting agents.
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    Funded Activity

    Investigation Of Novel Mechanisms Regulating Platelet Reactivity During Haemostasis And Thrombosis

    Funder
    National Health and Medical Research Council
    Funding Amount
    $221,210.00
    Summary
    Platelets are small specialised blood cells that are critical for normal blood clotting and blood vessel repair following injury. We are studying the processes that enable platelets to stick to the site of vessel injury and to each other to form a stable blood clot. These very processes, when unchecked, are responsible for the formation of harmful blood clots in the bloodstream that may block blood vessels in the heart or brain and result in a heart attack or stroke. Many factors control how big .... Platelets are small specialised blood cells that are critical for normal blood clotting and blood vessel repair following injury. We are studying the processes that enable platelets to stick to the site of vessel injury and to each other to form a stable blood clot. These very processes, when unchecked, are responsible for the formation of harmful blood clots in the bloodstream that may block blood vessels in the heart or brain and result in a heart attack or stroke. Many factors control how big and how rapidly a blood clot grows and whether it becomes harmful enough to lead to a heart attack or stroke. One of these factors is the level of platelet 'reactivity' or 'stickiness' . We are working towards a better understanding of how platelet reactivity is regulated and how this dictates the potential of a blood clot to become harmful. This knowledge will not only increase our knowledge of blood clot formation in health and disease, but also help in the development of new therapies for the prevention of heart attack and stroke.
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    Funded Activity

    Investigate The Role Of Platelet Von Willebrand Factor In Initiating Platelet Aggregation Under Flow

    Funder
    National Health and Medical Research Council
    Funding Amount
    $307,165.00
    Summary
    Platelets are small specialised blood cells that are essential for normal blood clotting and repair of damaged blood vessels following injury. We are studying the processes that enable platelets to stick to each other and to other cells to form a stable blood clot at the site of injury. The same processes, unchecked, are involved in the formation of harmful blood clots in the bloodstream that may block blood vessels in the heart or brain and result in a heart attack or stroke. Platelets stick to .... Platelets are small specialised blood cells that are essential for normal blood clotting and repair of damaged blood vessels following injury. We are studying the processes that enable platelets to stick to each other and to other cells to form a stable blood clot at the site of injury. The same processes, unchecked, are involved in the formation of harmful blood clots in the bloodstream that may block blood vessels in the heart or brain and result in a heart attack or stroke. Platelets stick to the blood vessel wall through specialised adhesive proteins. These adhesion proteins are stored within the platelet and expressed on the cell surface when the platelets stick to the blood vessel wall. In conditions such as Gray Platelet Syndrome, the platelets are unable to store adhesion receptors, resulting in impaired blood clot formation. A clearer understanding of how platelets stick to the blood vessel wall will not only increase our knowledge of blood clot formation in health and disease, but also with the potential development of new therapies for the prevention of heart disease and stroke.
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    Funded Activity

    Stress, Tyrosine And Cognitive Function

    Funder
    National Health and Medical Research Council
    Funding Amount
    $274,352.00
    Summary
    How well people perform in everyday situations is often determined by memory function. When required to perform under stress memory performance is often affected. The effect of a psychological stress test on memory function in healthy volunteers and the ability of a dietary supplement, tyrosine, to prevent the effects will be studied. The data may suggest that depletion amino acids is responsible for the decrements in performance that are evident after an acute stressor.
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    Funded Activity

    Central Control Of Stress-induced Changes In Immune Function.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $411,724.00
    Summary
    LONG-TERM STRESS CAN ALTER OUR BRAIN'S ATTEMPTS TO FIGHT INFECTION Long-term stress is often blamed for causing illness but precisely how this occurs is now only beginning to be realised. It is especially disturbing that long-term stress can increase one's susceptibility to infections. Stress can alter the way our brain can help deal with assaults by bacteria and viruses. Normally, at the start of an infection, we release a hormone called cortisol from our adrenal glands. A low level of cortisol .... LONG-TERM STRESS CAN ALTER OUR BRAIN'S ATTEMPTS TO FIGHT INFECTION Long-term stress is often blamed for causing illness but precisely how this occurs is now only beginning to be realised. It is especially disturbing that long-term stress can increase one's susceptibility to infections. Stress can alter the way our brain can help deal with assaults by bacteria and viruses. Normally, at the start of an infection, we release a hormone called cortisol from our adrenal glands. A low level of cortisol in our body is beneficial because it can prevent the infection from taking hold in our body and spreading. However if we are chronically stressed our brains tell the adrenal glands to secrete excessive amounts of cortisol over long periods of time and this imbalance can actually hinder the ability of one's immune system to fight an infection. The unfortunate consequence is that the infection is more likely to win the battle and spread to cause further havoc. The present study will identify which areas of the brain are important in driving the secretion of cortisol during infection and how long-term stress can influence those areas. Because we might be exposed to long-term psychological stress that is repeated regularly or irregularly we will determine which pattern of stress has the greatest effect. An investigation into how the brain operates during long-term stress and infection will help us develop ways to prevent stress from disrupting our immune systems.
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