This application will investigate the potential for nanomaterials to have adverse effects on human health and to formulate approaches to screen nanomaterials for potential health risks, particularly those with a high likelihood for human exposure in Australia. Understanding how existing nanomaterials interact with biological systems will help determine the risk of adverse effects in the human population and identify those nanoparticles with little or no risk.
DAMAGE TO SPECIFIC MITOCHONDRIAL MEMBRANE PROTEINS DURING OXIDATIVE STRESS AND THE AGEING PROCESS
Funder
National Health and Medical Research Council
Funding Amount
$195,982.00
Summary
During the ageing process and exposure to certain drugs or chemicals, oxygen radicals are produced within cells and tissues. If unchecked, these cause damage to a number of cell components, resulting in tissue death. One target for oxygen radicals are proteins in mitochondria, the powerhouses of the cell that are responsible for meeting cell energy needs. It is well known that the ability of mitochondria to maintain energy supplies decreases in old age. Over the past decade, research has shown t ....During the ageing process and exposure to certain drugs or chemicals, oxygen radicals are produced within cells and tissues. If unchecked, these cause damage to a number of cell components, resulting in tissue death. One target for oxygen radicals are proteins in mitochondria, the powerhouses of the cell that are responsible for meeting cell energy needs. It is well known that the ability of mitochondria to maintain energy supplies decreases in old age. Over the past decade, research has shown that this is partly due to mutation of genes in the DNA which is found in mitochondria. However it is also very likely that the loss of function in mitochondria during the ageing process is also due to the accumulation of protein damage. Recent work in insects has shown that specific proteins in mitochondria are extensively damaged during the ageing process and-or exposure to oxygen radicals. In higher organisms such as mice, however, exactly which mitochondrial proteins are targeted by oxygen radicals is unknown. This work will investigate the likelihood that proteins located in membranes of mitochondria are targets for damage by oxygen radicals and during the ageing process. Furthermore, since oxygen radicals readily attack polyunsaturated fatty acids in cell membranes, we are investigating the likelihood that toxic substances (unsaturated aldehydes) formed during membrane damage contribute to the damage to mitochondrial proteins during the ageing process.Read moreRead less
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.
Structure, Function And Regulation Of Human Cytosolic Sulfotransferases
Funder
National Health and Medical Research Council
Funding Amount
$265,500.00
Summary
The sulfotransferase family of enzymes serve an important role in the metabolism of drugs and foreign chemicals. They also metabolise a range of chemicals that are normally present in the body such as hormones and substances that are involved in brain function (neurotransmitters). Observations from clinical studies suggest that differences in sulfotransferases activities may be a causal factor in the incidence of certain types of cancer and neurodegenerative diseases. Recent advances in understa ....The sulfotransferase family of enzymes serve an important role in the metabolism of drugs and foreign chemicals. They also metabolise a range of chemicals that are normally present in the body such as hormones and substances that are involved in brain function (neurotransmitters). Observations from clinical studies suggest that differences in sulfotransferases activities may be a causal factor in the incidence of certain types of cancer and neurodegenerative diseases. Recent advances in understanding the molecular biology of these enzymes have shown us that multiple forms of sulfotransferase existed within the body. In this area my laboratory has been at the forefront of the cloning and characterisation of these enzymes. Indeed, we were the first laboratory to clone the major human sulfotransferase (SULT1A3) responsible for the metabolism of brain neurotransmitters. We have also used new technology to determine the shape of this important enzyme. At the time of writing my laboratory has characterised a total seven human sulfotransferases but unlike SULT1A3, our knowledge of the functional significance of the other six sulfotransferase is poorly understood. Further, our knowledge of what regulates the amount of sulfotransferase in different tissues is practically nonexistent. The thrust of this project is to extend our studies on the physiological function of these enzymes and also through the use of molecular biology techniques understand what controls the level of their expression in different human tissues. This knowledge will provide a basis for understanding the role of sulfotransferases play in drug and chemical metabolism. It will also aid our understanding of their role in hormone and neurotransmitter metabolism and help determine whether they are involved in such diseases as cancer and neurodegenerative diseases.Read moreRead less