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
Evaluation Of Factor Va From The Venom Of The Australian Brown Snake As A Topical And Systemic Anti-bleeding Agent
Funder
National Health and Medical Research Council
Funding Amount
$113,742.00
Summary
Anti-bleeding agents are important pharmaceuticals for use in truama, surgery and several medical conditions to reduce blood loss and the need for blood transfusion. Some Australian snakes contain in their venom a powerful blood clotting agent. This agent mimics the human clotting machinery. In this project, we plan to test purified components of snake venom for an ability to clot human blood. We will undertake laboratory test-tube experiments as well as using an animal model after ethical appro ....Anti-bleeding agents are important pharmaceuticals for use in truama, surgery and several medical conditions to reduce blood loss and the need for blood transfusion. Some Australian snakes contain in their venom a powerful blood clotting agent. This agent mimics the human clotting machinery. In this project, we plan to test purified components of snake venom for an ability to clot human blood. We will undertake laboratory test-tube experiments as well as using an animal model after ethical approval. This project seeks to capture some of the genetic blueprint of an Australian snake, for human benefit by developing a new therapeutic agent based on a venom component. If the experiments are successful, the next stage will be further testing of efficacy and toxicity before seeking approval for clinical trials. The research is supported by the Australian pharmaceutical company QRx Pharma Pty Ltd who will work with Uniquest Pty Ltd to protect intellectual property generated in the project.Read moreRead less
Platelet Glycoprotein Proteolysis: Novel Mechanisms And Risk Factors
Funder
National Health and Medical Research Council
Funding Amount
$441,473.00
Summary
Platelets are the richest source of amyloid precursor protein (APP) in the body. Platelet ADAM10 regulates both the expression and function of the major platelet collagen receptor GPVI, and protective APP processing. Coagulation protein Factor X has a role in activation of ADAM10. This activation is disrupted in blood that has been treated with direct oral anticoagulant (DOAC) rivaroxaban. This grant will investigate the implications for people taking rivaroxaban on regulation of APP and GPVI.
The Ghost In The Machine: Understanding How Haemostasis Is Regulated By Allosteric Disulphide Bonds
Funder
National Health and Medical Research Council
Funding Amount
$898,008.00
Summary
Genes encode proteins, which are the machinery of life. All life forms make proteins that contain bonds between pairs of cysteine amino acids called disulphide bonds. Prof Hogg has discovered a type of disulphide bond, the allosteric disulphide, which controls how proteins work by breaking or forming in a precise way. His research aim is to define how haemostasis is controlled by allosteric disulphides. Haemostasis gone wrong leads to heart attack and stroke.
Evaluation Of New Biomarkers Of Coagulation In High Risk Cardiovascular Population
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Predicting the cardiovascular risk of an individual remains challenging despite the current advances and to date, there is no available laboratory testing that accurately reflects an individual’s clotting profile. This prospective study aims to address this with the use of global coagulation assay as a novel tool for individual cardiovascular risk prognostication and management, as well as demonstrate the compensatory mechanism between the different arms of Virchow's triad.
Antiphospholipid Antibodies, Beta 2-Glycoprotein I And Control Of Coagulation.
Funder
National Health and Medical Research Council
Funding Amount
$471,000.00
Summary
Antiphospholipid antibodies are associated with an autoimmune condition characterised by the presence of clots and recurrent miscarriages. Although the name implies that the antibodies bind phospholipid the disorder is characterised by circulating antibodies which bind a protein in the blood known as Beta 2-Glycoprotein I. The exact role of Beta 2-GPI in the body has not been determined, although there are numerous studies looking at this protein. This protein has been thought to be important in ....Antiphospholipid antibodies are associated with an autoimmune condition characterised by the presence of clots and recurrent miscarriages. Although the name implies that the antibodies bind phospholipid the disorder is characterised by circulating antibodies which bind a protein in the blood known as Beta 2-Glycoprotein I. The exact role of Beta 2-GPI in the body has not been determined, although there are numerous studies looking at this protein. This protein has been thought to be important in controlling the clotting system in humans and other mammals. The evidence for this has been contradictory, however, we have recently made a major new finding on the function of this protein on the clotting system. We will be using sophisticated molecular biology techniques to further characterise the role that Beta 2-GPI has in controlling clotting factors in the body. We have been able to eliminate the gene for Beta 2-GPI in mice thus deriving mice that do not produce any Beta 2-GPI protein. These mice are called Beta 2-GPI knockout mice and will be an ideal animal model to examine the function of Beta 2-GPI and its new role in controlling the clotting cascade by targetting a specific part of this pathway. In addition, these findings may be able to provide new information on how Beta 2-GPI controls clotting factors and the effect of antiphospholipid antibodies on this system, which may lead to new treatments for antiphospholipid antibodies and more generally clotting disorders.Read moreRead less
Factor XII Dependent Coagulation, Thrombin And Platelet Glycoprotein 1ba In Arterial Thrombosis And Bleeding Disorders
Funder
National Health and Medical Research Council
Funding Amount
$104,664.00
Summary
Clot formation is the key event underlying heart attacks and strokes. There is new data that Factor XII (FXII) can play an important role in clot formation-thrombosis. We aim to examine the role FXII plays in clot formation, in particular the role of FXII in thrombin generation, which is the central event of clot formation, and its interaction with platelet glycoprotein 1ba (another important molecule in thrombosis). New insights into clotting and new therapies can result from our research.