Plasmin is a complex enzyme that performs major roles in removal of blood clots, wound healing and in tumor metastasis. Here we will understand how plasmin function is regulated at the molecular level. These key insights will be of future use in the development of therapeutics targeting the plasmin system in cancer and clotting diseases.
New Approaches To Improve Thrombolysis In Ischaemic Stroke
Funder
National Health and Medical Research Council
Funding Amount
$586,076.00
Summary
Ischaemic stroke is caused by the presence of a blood clot in the brain. The removal of these clots is achieved using an enzyme called tissue-type plasminogen activator (t-PA). While this agent is effective if given to patients within 4.5h of stroke onset, delayed administration can cause cerebral bleeding. This project is to understand how t-PA promotes these unwanted effects in the brain and to devise novel approaches to extend the time window of t-PA administration in these patients.
Proteases And Protease-inhibitor Complexes As Modulators Of Traumatic Brain Injury Severity
Funder
National Health and Medical Research Council
Funding Amount
$613,311.00
Summary
Traumatic brain injury (TBI) is a significant cause of mortality and morbidity in Australia, affecting approximately 21,800 Australians annually. A large number of survivors have permanent neurological deficits, causing adverse effects on lifestyle and family relationships and placing a significant burden on the health system. In this project we will address a novel means to improve TBI outcome by targeting two linked enzyme systems that together have been shown to be deleterious in this conditi ....Traumatic brain injury (TBI) is a significant cause of mortality and morbidity in Australia, affecting approximately 21,800 Australians annually. A large number of survivors have permanent neurological deficits, causing adverse effects on lifestyle and family relationships and placing a significant burden on the health system. In this project we will address a novel means to improve TBI outcome by targeting two linked enzyme systems that together have been shown to be deleterious in this condition.Read moreRead less
The Role Of Clostridium Difficile Spore Surface Structures In Initiating Gastrointestinal Infection And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$467,556.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with more virulent isolates emerging overseas since 2000. These strains were detected in Australia in 2010 and are now spreading throughout our hospitals. This project will increase our understanding of how these strains are transmitted to susceptible hosts and why they are so harmful, which is critical for the development of better strategies for preventing and treating these infection ....Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with more virulent isolates emerging overseas since 2000. These strains were detected in Australia in 2010 and are now spreading throughout our hospitals. This project will increase our understanding of how these strains are transmitted to susceptible hosts and why they are so harmful, which is critical for the development of better strategies for preventing and treating these infections.Read moreRead less
Antibody Targeted Thrombin-activatable ?-plasminogen Fusion Proteins And Nanocapsules For The Treatment Of Acute Thrombosis
Funder
National Health and Medical Research Council
Funding Amount
$536,951.00
Summary
The clinical consequences of atherosclerosis such as myocardial infarction and stroke are the major cause of mortality and morbidity in Australia. Clot dissolving agents have been proven to be beneficial in patients with acute myocardial infarction, vein thrombosis, pulmonary embolism, and stroke. However, the currently available drugs have major limitations in efficacy and in safety. The aim of this project is to develop novel drugs that have the potential to improve both significantly.
Urokinase Is A Key Mediator Of Airway Inflammation And Tissue Remodelling In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$556,425.00
Summary
The scarring of airway tissue in asthma increases the difficulty of breathing. There is no effective treatment for airway scarring in severe asthma. This study looks at how proteins involved in dissolving blood clots influence wound healing and scarring in the airways. A better understanding of airway tissue scarring will lead to possible treatments for more serious forms of asthma which remain a major health and economic burden to our community.
Role Of The Host Fibrinolytic System In Invasive Group A Streptococcal Disease
Funder
National Health and Medical Research Council
Funding Amount
$531,444.00
Summary
The flesh-eating bacterium group A streptococcus (GAS) is estimated to cause 700 million cases of self-limiting disease, and 600,000 cases of serious invasive disease each year. Approximately 25% of invasive infections are fatal. We have shown that GAS are able to hijack the host fibrinolytoc system to cause severe invasive infections. We plan to further examine the details of how this contributes to GAS disease. This research may contribute to the future devlopment of new therapeutics.