Macrophage Uncoupling Protein-2 Regulation And Expression In Inflammatory Joint Disease And Hyperoxic Lung Damage
Funder
National Health and Medical Research Council
Funding Amount
$270,013.00
Summary
Oxygen radicals (OR) are made by white blood cells (WBC) when they protect against microbes and cancer cells. However, excessive production also damages normal tissue, for example in lungs that receive too much oxygen (hyperoxic lung damage) or in inflamed joints. One type of WBC, the macrophage has a protein named UCP2, that limit the amount of OR formation. This project aims to find out how macrophages activate UCP2 and whether they do so in inflammatory arthritis and hyperoxic lung damage.
Pharmacological Strategy For Blocking Lung Cell Damage By Toxic Smoke Constituents.
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
People retrieved from burning buildings or other hazardous situations involving fires are often at risk of death due to the effects of inhaled smoke. This reflects the presence of some very toxic substances in smoke that are products of the combustion of wood, vegetation and synthetic building materials. The most toxic substance present within smoke is acrolein, a very reactive chemical that attacks cells in the lining of the lung. This can result in a life-threatening condition known as oedema, ....People retrieved from burning buildings or other hazardous situations involving fires are often at risk of death due to the effects of inhaled smoke. This reflects the presence of some very toxic substances in smoke that are products of the combustion of wood, vegetation and synthetic building materials. The most toxic substance present within smoke is acrolein, a very reactive chemical that attacks cells in the lining of the lung. This can result in a life-threatening condition known as oedema, where the lung is flooded with fluids and is unable to perform its respiratory function. At present, the clinical approaches used to treat smoke inhalation victims are mostly directed against offsetting the symptoms of lung injury and do not take into account the role of lung cell injury by toxic substances in smoke such as acrolein. This project will provide a better understanding of the chemical events underlying the injury caused by smoke to lung cells, and also into possible drug strategies for treating victims of smoke inhalation. The work will explore the ability of a range of compounds that are chemically related to a blood pressure-lowering medicine (hydralazine) to protect lung cells against such smoke-induced damage. The work will employ a range of modern research techniques to understand the events occurring in lung cells exposed to smoke. Once this is understood, these approaches will be used to test the various drug compounds for their abilities to prevent the death of cells exposed to smoke or its toxic constutuent acrolein. This work will yield new information on a series of compounds concerning their ability to block the toxicity of smoke to lung cells. The goal is to identify one or two molecules that can be carried forward to testing in smoke-exposed animals.Read moreRead less
Optimisation Of The Supportive Care Of Adults With Severe Falciparum Malaria
Funder
National Health and Medical Research Council
Funding Amount
$239,346.00
Summary
In the last two decades the care of patients with severe malaria has been revolutionised by the discovery of new drugs that reduce the chance of dying by 30% when compared to the previous standard treatments. However even with the use of these drugs, up to 30% of adults and 10% of children with severe malaria will still die from the disease. We need a greater understanding of how malaria harms people so that we might develop new drugs and treatment strategies to improve outcomes.
An In-vivo Model Of Acquired Chemoresistance In Small Cell Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$363,827.00
Summary
Lung cancer is a common and lethal disease in our community. In this project, we explore how a very aggressive form of lung cancer becomes resistant to chemotherapy. To do this, we use a new mouse model of lung cancer in which we can study how human lung cancer cells develop resistance to chemotherapy in vivo. Understanding these pathways will help us to better treat lung cancer with chemotherapy.
Mechanisms Of Epithelial Damage By The Noxious Smoke Constituent Acrolein
Funder
National Health and Medical Research Council
Funding Amount
$668,813.00
Summary
Due to increasing use of reactive chemicals by terrorists (e.g. chlorine gas), their effects on the lung are receiving increasing attention in the global toxicology community. This project focusses on acrolein, the major cytotoxic substance present in smoke produced on combustion of organic matter. We will explore the mechanisms whereby acrolein and high doses of smoke cause the lung to lose its watertight properties, and also test ways of preventing such damage with drugs.
NEURAL MODULATION OF HEARING LOSSES INDUCED BY LOUD SOUND
Funder
National Health and Medical Research Council
Funding Amount
$290,500.00
Summary
Loud sounds, from occupational and recreational sources, are the most common threat to hearing and can result in temporary hearing losses (as might be experienced after an evening at a noisy pub or concert) or permanent hearing losses (after prolonged or multiple loud sounds, as for example in a noisy work environment). Noise reduction programs are either not always possible or effectively applied. A parallel strategy is the study of biological mechanisms that may ameliorate hearing damage, with ....Loud sounds, from occupational and recreational sources, are the most common threat to hearing and can result in temporary hearing losses (as might be experienced after an evening at a noisy pub or concert) or permanent hearing losses (after prolonged or multiple loud sounds, as for example in a noisy work environment). Noise reduction programs are either not always possible or effectively applied. A parallel strategy is the study of biological mechanisms that may ameliorate hearing damage, with a view to optimising such mechanisms. I propose to build on seminal Australian work to examine how one such system, nerves from the brain to the inner ear (the site of most damage from loud sounds), modulates hearing losses caused by loud sounds. Early studies indicated these nerves could protect from damage induced by short-lasting loud sound and this has led to international interest in functional applications of such protection to reduce hearing damage suffered by humans. However, my recent work indicates the nerves exert complex protective and exacerbative effects to loud sounds similar to common trauma or occurring under conditions similar to common trauma. They even exacerbate hearing losses due to loud sound, especially when there is an imbalance in hearing sensitivity in the two ears (bilateral) similar to what is common in humans. These findings make it critical that functional application be delayed until the full range of effects exerted by the nerves is understood. I propose to elucidate the novel complex effects of these nerves to loud sound. Specific aims are: (1) To understand effects of these pathways to loud sounds like those encountered by humans, (2) To investigate how chronic imbalanced bilateral hearing sensitivity, like that common in humans, alters effects of the nerves and when they change from being protective to exacerbative, (3) To adduce how an atraumatic sound affects hearing losses due to later loud sound and the role played by these nerves.Read moreRead less
Allergen-sensitzation And Environmental Exposures In Early Life Interact Synergistically To Alter Lung Growth
Funder
National Health and Medical Research Council
Funding Amount
$425,088.00
Summary
Asthma develops as the result of complex interactions between genetic susceptibilities and environmental exposures. Approximately 40% of 6-year-old children in Perth are sensitized to inhaled allergens, however, only half of these have asthma. Allergic sensitization per se is therefore insufficient for the development of persistent asthma. A second hit, associated with lung inflammation in early life, increases this risk several fold. This second hit could come from viral infection or from other ....Asthma develops as the result of complex interactions between genetic susceptibilities and environmental exposures. Approximately 40% of 6-year-old children in Perth are sensitized to inhaled allergens, however, only half of these have asthma. Allergic sensitization per se is therefore insufficient for the development of persistent asthma. A second hit, associated with lung inflammation in early life, increases this risk several fold. This second hit could come from viral infection or from other inflammatory stimuli such as exposure to cigarette smoke, air pollutants and vehicle exhaust emissions. The timing of this second hit may well be important, particularly if it is early while the lungs are still growing and developing. The aim of this project is to examine interactions between allergen sensitization and exposure to environmental hazards in early life using a mouse model of allergic inflammation. We will test the hypothesis that the combination of allergic sensitization and viral infections in early life alter lung growth, airway function and airway hyperresponsiveness, however, exposure to air pollutants can not provide the 'second hit required to induce persistent asthma. Determining the role viral infection and environmental pollution have early in life may provide us with a strategy for intervention that could prevent life-long changes in respiratory function and airway hyperresponsiveness.Read moreRead less
Circulatory Biomarkers For Idiopathic Pulmonary Fibrosis: Improving Patient Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$841,625.00
Summary
We are going to find molecules in the blood that would improve the diagnosis and treatment of a lung condition called Idiopathic Pulmonary Fibrosis (IPF). The project brings together well characterized patients from the Australian IPF registry, blood samples we have collected from them and cutting edge technologies to complete this project.
A Novel Strategy For The Treatment Of Chronic Skeletal Joint Defects
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Skeletal joint injuries often heal poorly with current treatment approaches and lead to the onset of osteoarthritis. This project will produce a synthetic graft with unique properties to mimic the complex structure of joint tissues, and high bioactivity to induce optimal healing of the joint. This graft will constitute a viable alternative for the treatment of skeletal joint defects, resulting in significant healthcare benefits and improved long-term outcomes.