Role For Zinc And ZIP2 In The Action Of Nitric Oxide And In Vascular Protection Against Cigarette Smoke And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$685,941.00
Summary
The NO/cGMP signalling pathway, which is central to cardiovascular physiology and protection against disease, is only fully effective when there are adequate levels of zinc in the vascular endothelium. This is especially important where zinc stores are depleted (elderly, smokers, diabetics and kidney disease). There is an urgent clinical need to implement strategies to monitor vascular Zn status. This application will explore the underlying science and translate these to the clinic.
Alveolar Macrophage Zinc And Zinc Transporters And Their Role In Phagocytosis
Funder
National Health and Medical Research Council
Funding Amount
$288,975.00
Summary
Zinc is an essential dietary component that serves a number of functions in the lungs. It is both an anti-oxidant and anti-inflammatory agent. Some airway inflammatory diseases such as emphysema may involve a critical loss of lung zinc. We believe that cigarette smoke causes the loss of zinc and this prevents the lung macrophages from working properly to clear bacteria and dead cells. This will provide a foundation for our long term goals of better clinical management of emphysema.
Airway Epithelial IAPs And Their Interaction With Zn Ions
Funder
National Health and Medical Research Council
Funding Amount
$260,779.00
Summary
The air we breathe contains a variety of harmful substances. Damage to the lining involves death of the ciliated cells that line the airways. We have shown that zinc protects these cells from premature death. This application focuses on a family of proteins called IAPs which bind zinc and regulate cell death in other tissues. This project focusses on how the IAPs and Zn may act together to mainitain healthy airways and how abnormalities of these may occur in people with asthma.
Role Of Zinc In The Respiratory Epithelium And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$224,250.00
Summary
This project will use a panel of Zinquin-derived Zn fluorophores developed in our laboratory, as well as probes for the mammalian family of vesicular ZnT transporters, to carry out a study of the normal physiology of Zn in the respiratory system and potential abnormalities of this in patients with chronic inflammatory respiratory disease (asthma, COPD, chronic smoking). Chronic inflammatory diseases of the respiratory tract affect a significant proportion of the Australian community. For example ....This project will use a panel of Zinquin-derived Zn fluorophores developed in our laboratory, as well as probes for the mammalian family of vesicular ZnT transporters, to carry out a study of the normal physiology of Zn in the respiratory system and potential abnormalities of this in patients with chronic inflammatory respiratory disease (asthma, COPD, chronic smoking). Chronic inflammatory diseases of the respiratory tract affect a significant proportion of the Australian community. For example, asthma affects 12% of adults and amongst these, 15% waken weekly or more often with their asthma while 6% are hospitalized annually. There is a need to understand the basic mechanisms underlying these diseases so that new strategies can be developed to modify bronchocondtriction and inflammation. The project will provide new knowledge concerning the physiology of Zn in the respiratory epithelium and interactions between Zn deficiency and oxidants on injury in the respiratory tract. The usefulness of easily accessible nasal epithelial cells as a measure of Zn and Zn transporter levels deeper in the respiratory tract will be assessed. The project encompasses a number of fields and utilizes in vitro cellular and animal models, as well as tissues from human subjects.Read moreRead less
Characterising Signals Important For Lymphangiogenesis During Development And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$604,938.00
Summary
Lymphatic vessels are a vital component of the cardiovascular system. Abnormalities in the growth and development of lymphatic vessels are associated with human disorders including cancer, lymphoedema and inflammatory diseases. The focus of this application is to characterise signals that direct the construction of lymphatic vessels, with the aim of identifying targets to which novel therapeutics for the treatment of lymphatic vascular diseases could be generated.
Defining The Role Of GATA2 In Lymphatic Vascular Development As A Means To Understanding How GATA2 Mutations Predispose To Human Lymphedema.
Funder
National Health and Medical Research Council
Funding Amount
$718,890.00
Summary
We have discovered that mutations in the transcription factor GATA2 result in human primary lymphedema, a debilitating disorder resulting from the failure of lymphatic vessels to return tissue fluid to the bloodstream. The goal of this application is to define the role of GATA2 in lymphatic vessels, in order to understand how GATA2 mutations cause lymphedema. Ultimately, we aim to identify targets to which desperately needed therapeutics for the treatment of lymphedema could be generated.
Deciphering The Transcriptional Program That Instructs Lymphatic Endothelial Cell Fate.
Funder
National Health and Medical Research Council
Funding Amount
$541,950.00
Summary
Lymphatic vessels are essential to maintain fluid balance in most tissues of the human body. Further the lymphatic vasculature plays a central role during cancer and contributes to tumour metastasis. Despite this integral function in health and disease little is known about the molecular programs that coordinate gene expression to build a functional vasculature. This research project will address this gap in our knowledge and will open up new therapeutic avenues for lymphatic vascular disorders
Regulation Of VEGFR Trafficking And Signal Transduction By The Ubiquitin Ligase Nedd4
Funder
National Health and Medical Research Council
Funding Amount
$388,347.00
Summary
Our recent work has discovered that the Nedd4 gene is crucial for the growth and development of blood vessels and lymphatic vessels. Our data suggest that Nedd4 controls vessel growth by regulating the levels and signalling activity of the key vascular growth factor receptors VEGFR-2 and VEGFR-3. The goals of this proposal are to define precisely how Nedd4-1 regulates the activity of these receptors and how VEGFR signalling could be better targeted to treat vascular disorders.
Brain Repair Following Stroke: The Role Of Npas4, A Neural-specific Transcription Factor
Funder
National Health and Medical Research Council
Funding Amount
$611,053.00
Summary
Stroke is the #1 cause of adult disability in Australia and #2 cause of death. About 60,000 Australians suffer a stroke each year while about 250,000 live with the disabilities of stroke, costing over $2B/year. The Queen Elizabeth Hospital and University of Adelaide will study why the Npas4 gene switches on after stroke and the role it plays in brain repair. Future health benefits may be tests to help improve stroke outcome in patients and therapy to decrease loss of brain cells after stroke.
Development Of Engineered Novel Growth Factors For Infertility Treatment
Funder
National Health and Medical Research Council
Funding Amount
$410,439.00
Summary
Infertility comes at an enormous social and financial cost to Australian society. The aim of this proposal is to improve the success rate of an innovative technology that matures eggs in the laboratory and so eliminates the need for the hormones normally used in IVF. To achieve this a newly discovered egg-secreted protein first has to be produced in the laboratory.