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.
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.
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
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.
Investigating The Antimicrobial Activity Of Zinc At The Host-pneumococcal Interface
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Streptococcus pneumoniae is a human-only bacterium that is responsible for killing more than one million people every year. This project will analyse how the human immune system fights this bacterium, and subsequently, how the bacteria manages to subvert these attacks and survive in the human host. This will provide crucial information for developing new drugs against this pathogen, in an attempt to combat the ever-increasing problem of antibiotic resistance.
Exploiting Increased Autophagy In Bronchial Epithelial Cells: A New Therapeutic Approach For Chronic Obstructive Pulmonary Disease (COPD)
Funder
National Health and Medical Research Council
Funding Amount
$724,161.00
Summary
COPD is incurable, a leading cause of death, and new therapies are urgently needed. Autophagy is a cell response to cell stress conditions, however increased autophagy is harmful. We will investigate the association of increased autophagy with COPD and smoking and evaluate therapies that can reduce autophagy, including zinc-related drugs and novel antibiotics that have been modified to lose their anti-bacterial activity.
Extreme temperature monitoring for minerals and metals processing. This project aims to extend the capabilities of the optical fibre temperature sensor technology developed by the research team, based on microstructured optical fibres and femtosecond laser ablation fibre Bragg gratings, to conduct a range of measurements inside industrial furnace environments that are impossible using existing technology. This device will also be validated within the furnaces located at the minerals and metals p ....Extreme temperature monitoring for minerals and metals processing. This project aims to extend the capabilities of the optical fibre temperature sensor technology developed by the research team, based on microstructured optical fibres and femtosecond laser ablation fibre Bragg gratings, to conduct a range of measurements inside industrial furnace environments that are impossible using existing technology. This device will also be validated within the furnaces located at the minerals and metals processing facility operated by Nyrstar in Port Pirie. This project is designed to enable smelter operators to improve production efficiency, reduce energy consumption, and minimise equipment failure.Read moreRead less
Epilepsy: Molecular Basis And Mechanisms In The Era Of Functional Genomics
Funder
National Health and Medical Research Council
Funding Amount
$12,062,533.00
Summary
The team comprises of neurologists with a special interest in epilepsy (both adult and child) molecular geneticists, physiologists and brain imaging specialists. The team leads the world in the discovery of the genetic causes of epilepsy and epilepsy associated with intellectual disability. The team will continue to identify the genes underlying epilepsy, and study how genetic variations result in the development of seizures and will continue to develop advanced imaging techniques for these stud ....The team comprises of neurologists with a special interest in epilepsy (both adult and child) molecular geneticists, physiologists and brain imaging specialists. The team leads the world in the discovery of the genetic causes of epilepsy and epilepsy associated with intellectual disability. The team will continue to identify the genes underlying epilepsy, and study how genetic variations result in the development of seizures and will continue to develop advanced imaging techniques for these studies. This will include extensive laboratory studies, including the development of mice with the exact mutations that we find in the human condition. Stateof-the-art imaging techniques with magnetic resonance and positron emission tomography are used in human subjects to further understand the effects of the mutations on the structure and function of the brain. This will allow deep understanding of how seizures develop and may lead to new diagnostic methods and treatments. The laboratory and clinical aspects of the research are tightly integrated in this internationally leading collaborative program.Read moreRead less
I am a molecular geneticist with a main research focus in the identification and characterisation of genes and molecular pathways involved in intellectual disability and epilepsy.
Identifying Target Genes For Novel Anti-epileptic Therapies In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$469,802.00
Summary
Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not respo ....Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not responding to current therapy. This project is designed to identify new biologic pathways which may be interrupted with drugs to prevent seizures in people with epilepsy. This project uses a procedure to induce mutations into genes in mice and then screens for mice which do not seize when challenged with a drug which generates seizures in mice. Genetic studies will identify the mutated genes and these will be used as potential targets for new therapies or will identify new biological pathway which should expand the use of future anti-epileptic drugs.Read moreRead less