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
Unified Model For Group A Streptococcal Invasive Disease Initiation.
Funder
National Health and Medical Research Council
Funding Amount
$605,221.00
Summary
Streptococcus pyogenes (group A streptococcus; GAS) is a bacterium that causes human skin and throat infections as well as highly invasive diseases including necrotising fasciitis and streptococcal toxic shock-like syndrome. We have recently discovered the trigger mechanism for GAS invasive disease. We hypothesise that the initial host response at the site of infection selects for a GAS invasive phenotype. We propose to examine the chain of events which result in tissue invasion in order to unde ....Streptococcus pyogenes (group A streptococcus; GAS) is a bacterium that causes human skin and throat infections as well as highly invasive diseases including necrotising fasciitis and streptococcal toxic shock-like syndrome. We have recently discovered the trigger mechanism for GAS invasive disease. We hypothesise that the initial host response at the site of infection selects for a GAS invasive phenotype. We propose to examine the chain of events which result in tissue invasion in order to understand these disease processes and allow the development of future therapeutic interventions.Read moreRead less
Role Of Bacteriophage-encoded Streptodornase In Invasive Disease Caused By Diverse Group A Streptococcal M Serotypes.
Funder
National Health and Medical Research Council
Funding Amount
$832,544.00
Summary
Streptococcus pyogenes (group A streptococcus, GAS) is estimated to cause ~700 million cases of self-limited throat or skin infection each year worldwide. Invasive GAS disease occurs in approximately 1-1000 cases, with associated mortality of 25%. We have recently discovered that a viral infection can reprogram GAS for invasive disease propensity. We will investigate whether this phenomenon is widespread, in order to understand this process and develop future therapeutics.
Immunotoxic Effects Of Engineered Nanomaterials Used In The Australian Workplace
Funder
National Health and Medical Research Council
Funding Amount
$586,816.00
Summary
Certain engineered nanomaterials are more toxic than their bulk material forms. We urgently need the ability to re-engineer these nanomaterials to reduce their toxicity and potential health risks, but lack the necessary knowledge. This project directly addresses the NHMRC Strategic Initiative on Nanotechnology and Health, by providing essential information for designing safer nanomaterials from systemically studying the immune effects of metal oxide nanoparticles used in Australian industry.
Understanding And Preventing Secondary Degeneration Following CNS Injury
Funder
National Health and Medical Research Council
Funding Amount
$409,147.00
Summary
After neurotrauma, tissue escaping initial injury undergoes secondary degeneration; tissue loss spreads, function worsens. In the complex brain and spinal cord it is difficult to distinguish vulnerable tissue. Using the visual system as a model I will precisely identify cells and processes of secondary degeneration, determine if vulnerable tissue can be rescued by drugs stopping toxic calcium influx and if rescued circuits work properly. The work has implications for neurotrauma and glaucoma.
ALCOHOL AND IMPAIRED LIVER REGENERATION: EFFECTS ON MITOGENIC SIGNALING PATHWAYS
Funder
National Health and Medical Research Council
Funding Amount
$365,295.00
Summary
Patients who regularly consume alcohol are slow to recover from liver injury because alcohol poisons the liver's capacity to regenerate itself (grow back). Hence patients with alcohol-induced liver disease have a high mortality and prolonged hospital stays. The applicants have been supported by NHMRC to study how alcohol impairs liver regeneration. They found that the effect is at the level of cell surface receptors for the growth factors that control liver regeneration. Alcohol alters the funct ....Patients who regularly consume alcohol are slow to recover from liver injury because alcohol poisons the liver's capacity to regenerate itself (grow back). Hence patients with alcohol-induced liver disease have a high mortality and prolonged hospital stays. The applicants have been supported by NHMRC to study how alcohol impairs liver regeneration. They found that the effect is at the level of cell surface receptors for the growth factors that control liver regeneration. Alcohol alters the function of these receptors. One major discovery has been that it damages the capacity to generate a rise in calcium within the cell, something that is fundamentally required for any cell to divide and reproduce itself. Thus when a rise in calcium was produced artificially (with chemicals to unlock the internal calcium stores), liver cells from alcohol-fed rats once more responded normally under the influence of growth factors and replicated themselves. The present work isdesigned to find out where this effect of calcium is exerted. The investigators believe that it is related to how other types of signals work, the so-called protein kinase pathways. These are cascades of one protein turning on (activating) the next down the line to ultimately switch on the genes that control cell growth. They will manipulate liver cells from alcohol-fed rats in culture to establish which of these pathways is most affected, and which is the most critical for the control of cell division genes. These studies will greatly advance our understanding about how alcohol impairs liver regeneration. They will give new insight into the control of liver cell growth and division that is such a crucial response of the liver to injury, vital for survival of the liver. This kind of knowledge will open the door for new treatments to be designed that can control liver growth - turn it back on when it has been poisoned, or turn it off when it is inappropriately vigorous and predisposing to liver cancer.Read moreRead less