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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.
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
Metal-Based Anti-inflammatory Drugs with High Efficacy and Low Side-Effects. Non-steroidal anti-inflammatory drugs (NSAIDs) have widespread human and veterinary applications for the treatment of arthritis and other inflammatory diseases, but their utility is limited by often severe gastrointestinal, renal and cardiac side-effects. The recently heralded COX-2 inhibitors have not lived up to their expectations in terms of efficacy and side-effects, therefore, there is a need to develop new potent ....Metal-Based Anti-inflammatory Drugs with High Efficacy and Low Side-Effects. Non-steroidal anti-inflammatory drugs (NSAIDs) have widespread human and veterinary applications for the treatment of arthritis and other inflammatory diseases, but their utility is limited by often severe gastrointestinal, renal and cardiac side-effects. The recently heralded COX-2 inhibitors have not lived up to their expectations in terms of efficacy and side-effects, therefore, there is a need to develop new potent, but safer, NSAIDs. This project is aimed at using the results from new lead compounds to design NSAIDs with much greater efficacy and much less side effects than those currently available.Read moreRead less
Characterization Of The Novel Drug And Xenobiotic Metabolizing UGT3A Enzyme Family
Funder
National Health and Medical Research Council
Funding Amount
$578,352.00
Summary
The elimination of chemicals made in the body or from environmental sources is essential for the maintenance of good health and the prevention of debilitating diseases. We have discovered two enzymes that use glucose and other sugars to detoxify fat-soluble chemicals. In this project we will study how these enzymes work and how they are regulated in the body. With this knowledge, we may be able to target the processes of drug and chemical detoxification to make them more efficient.
I am a molecular pharmacologist investigating how the body eliminates fat-soluble chemicals, including drugs, toxins, steroids and waste products of metabolism.
Using a battery of tests to evaluate the potential toxicity of remediated and unremediated soils and dusts contaminated with metals. An in vitro model simulating the intact and immature infant intestinal epithelium will be used to determine the changes in solubility and uptake of metals following in situ remediation processes. The earthworm and bacterial luminescence toxicity tests indicate the ecotoxicity of contaminated soils.
Many garden soils, household dusts, and industrial sites are conta ....Using a battery of tests to evaluate the potential toxicity of remediated and unremediated soils and dusts contaminated with metals. An in vitro model simulating the intact and immature infant intestinal epithelium will be used to determine the changes in solubility and uptake of metals following in situ remediation processes. The earthworm and bacterial luminescence toxicity tests indicate the ecotoxicity of contaminated soils.
Many garden soils, household dusts, and industrial sites are contaminated with lead, cadmium, and other metals. These pose a risk to human health, especially of children, and ecosystem health
These tests will be applied to prioritise sites where metal contamination exists and to evaluate the effectiveness of remediation techniques in reducing metal uptake and toxicity.Read moreRead less
Micro- and nano-particulate delivery systems for chemical and biological weapons: physical characterisation and risk assessment. Inert solid powder has been used as a carrier for chemical and biologically-active agents to increase their effectiveness in a range of applications such as chemical weapons, pesticides and insecticides. The aim of this research is to determine the influence of the physical characteristics of particulate delivery systems on their ability to deliver potentially toxic s ....Micro- and nano-particulate delivery systems for chemical and biological weapons: physical characterisation and risk assessment. Inert solid powder has been used as a carrier for chemical and biologically-active agents to increase their effectiveness in a range of applications such as chemical weapons, pesticides and insecticides. The aim of this research is to determine the influence of the physical characteristics of particulate delivery systems on their ability to deliver potentially toxic substances to exposed skin and through protective clothing. This data will provide the first step in the design and development of effective protective clothing/products and safety protocols to safeguard the health of Australians involved in the defence of Australia.Read moreRead less
Does Fresh Frozen Plasma In Russells Viper Bite Coagulopathy Reduce The Dose And Duration Of Antivenom Therapy?
Funder
National Health and Medical Research Council
Funding Amount
$622,344.00
Summary
This proposal seeks funding to undertake a trial of clotting factor replacement with low dose antivenom therapy in snake bite coagulopathy in Sri Lanka. The aim is to determine if factor replacement will result in a rapid return of clotting function, allow a smaller dose of antivenom and therefore reduce the potential risk of major bleeding and reactions to antivenom. This study will have international implications because globally snakebite coagulopathy is a major cause of morbidity and death .
Pharmacological and biochemical characterisation of Australian mygalomorph spider venoms. This project will increase our limited knowledge of Australian mygalomorph venoms by isolation, identification and characterisation of novel toxins in theraphosid and Northern mouse-spider venoms. Thereby, the scientific basis for the treatment of mygalomorph spider bites might be improved. Secondly, new insights into pharmacology and the potential development of novel therapeutics and molecular probes of t ....Pharmacological and biochemical characterisation of Australian mygalomorph spider venoms. This project will increase our limited knowledge of Australian mygalomorph venoms by isolation, identification and characterisation of novel toxins in theraphosid and Northern mouse-spider venoms. Thereby, the scientific basis for the treatment of mygalomorph spider bites might be improved. Secondly, new insights into pharmacology and the potential development of novel therapeutics and molecular probes of target molecules might be expected.Read moreRead less