Rational Optimisation of the Uptake of Metal-Based Anti-Cancer Agents by Tumours. In this project will develop an understanding of how anticancer drugs are taken up, distributed and modified in tumours. The information gathered will be of value to all those developing new anticancer drugs and we will then use it to develop new drugs that more selectively target tumours and therefore have reduced side effects. Successful development of less toxic anticancer agents would lead to less debilitating ....Rational Optimisation of the Uptake of Metal-Based Anti-Cancer Agents by Tumours. In this project will develop an understanding of how anticancer drugs are taken up, distributed and modified in tumours. The information gathered will be of value to all those developing new anticancer drugs and we will then use it to develop new drugs that more selectively target tumours and therefore have reduced side effects. Successful development of less toxic anticancer agents would lead to less debilitating treatment, more effective treatment, and an increase in the number of patients effectively treated. Effective anticancer drugs can also be very large income earners for Australia.Read moreRead less
Novel insecticidal neurotoxins from Australian spider venoms. Insecticidal toxins have considerable potential as novel biopesticides to combat the evolution of widespread insect resistance to classical chemical pesticides. This problem is increasing both in Australia and internationally. This study aims to isolate and pharmacologically characterise potent and selective insecticidal neurotoxins from Australian arachnids. Our laboratories will isolate neurotoxins from spider venoms, determine thei ....Novel insecticidal neurotoxins from Australian spider venoms. Insecticidal toxins have considerable potential as novel biopesticides to combat the evolution of widespread insect resistance to classical chemical pesticides. This problem is increasing both in Australia and internationally. This study aims to isolate and pharmacologically characterise potent and selective insecticidal neurotoxins from Australian arachnids. Our laboratories will isolate neurotoxins from spider venoms, determine their selectivity in insect and mammal bioassays, determine their primary and tertiary structures, and investigate their structure-function relationships by electrophysiological techniques. These functional and structural data will allow the future engineering, by molecular or synthetic procedures, of viral biopesticide analogues with increased potency, stability and selectivity.Read moreRead less
Characterisation of two-pore domain potassium channels: structure-function studies of the M1-P1 loops of TASK channels. TWIK-related Acid Sensitive K+ (TASK) channels are members of the novel class of two-pore domain potassium channel family. They are potently inhibited by local anaesthetics and have been implicated as having important roles in many pathophysiological conditions such as heart arrythmias, stroke, epilepsy, breast and other cancers. The in depth structural and functional character ....Characterisation of two-pore domain potassium channels: structure-function studies of the M1-P1 loops of TASK channels. TWIK-related Acid Sensitive K+ (TASK) channels are members of the novel class of two-pore domain potassium channel family. They are potently inhibited by local anaesthetics and have been implicated as having important roles in many pathophysiological conditions such as heart arrythmias, stroke, epilepsy, breast and other cancers. The in depth structural and functional characterisation of this class of potassium channels is of great importance as they are interesting targets for new therapeutic developments. Advancement of knowledge in the structure and function of these channels will underpin drug targeting that will aid preventative healthcare, allowing Australians to age well and age productively.Read moreRead less
Treating tuberculosis: targeted delivery of multidrug nano-suspensions. Tuberculosis (TB) is a lung disease of worldwide prevalence. Treatment times are long and mortality is high in children and the elderly. Current treatments are ineffective and drug resistant TB is a real pandemic threat. The project will develop a cost-effective nano-particle system that can be incorporated into conventional nebulisers for use worldwide.
Investigating the mechanisms of flavonoid actions on glycine receptors. The research to be conducted in this project will use state-of-the-art electrophysiological and molecular biological approaches to carefully characterise the actions of certain flavonoid compounds on the glycine-receptor channel. These compounds have recently been reported to act as modulators of ligand-gated ion channels, proteins integral to brain function and disease. However, no-one has studied in any detail the mechan ....Investigating the mechanisms of flavonoid actions on glycine receptors. The research to be conducted in this project will use state-of-the-art electrophysiological and molecular biological approaches to carefully characterise the actions of certain flavonoid compounds on the glycine-receptor channel. These compounds have recently been reported to act as modulators of ligand-gated ion channels, proteins integral to brain function and disease. However, no-one has studied in any detail the mechanisms by which these compounds act. By discovering their site and mechanisms of action we will further our understanding of these important proteins and their modulation, maintain Australia's significant expertise in this field and provide leads for future development of drugs with potential therapeutic value.Read moreRead less
Age-dependent effects of cannabinoids on emotion, cognition and vulnerablity to addiction. Cannabis is the most widely used illicit drug in Australia so understanding the effects of this drug is of great importance. There is little of no basic research on cannabis currently occurring in Australia. Yet such research is critical in resolving the ambiguities and difficulties inherent in our understanding of the drug. The importance of increasing our understanding of the long-term effects of the dr ....Age-dependent effects of cannabinoids on emotion, cognition and vulnerablity to addiction. Cannabis is the most widely used illicit drug in Australia so understanding the effects of this drug is of great importance. There is little of no basic research on cannabis currently occurring in Australia. Yet such research is critical in resolving the ambiguities and difficulties inherent in our understanding of the drug. The importance of increasing our understanding of the long-term effects of the drug on young developing brains is particularly evident. The information gained in the current project will serve to inform medical and scientific communities, government policy makers, as well as the broader Australian community. Read moreRead less
Radiolabelled MMP binding agents for the identification, quantification, and targeting of MMPs in central nervous system (CNS) disorders and tumours. Cancer and diseases of the central nervous system (CNS) represent two of the major health challenges facing Australia because of the aging population. In order to address these challenges we need to develop methods for identifying tumours and CNS diseases using non-invasive technologies and at an early stage so that treatments can be applied when t ....Radiolabelled MMP binding agents for the identification, quantification, and targeting of MMPs in central nervous system (CNS) disorders and tumours. Cancer and diseases of the central nervous system (CNS) represent two of the major health challenges facing Australia because of the aging population. In order to address these challenges we need to develop methods for identifying tumours and CNS diseases using non-invasive technologies and at an early stage so that treatments can be applied when they are most likely to work. In this project, we are developing new radiolabelled compounds that will enable the imaging of tumours, tumour metastases and CNS diseases states.Read moreRead less
Defining mechanisms of action of novel alpha-conotoxins at nicotinic receptor-channels. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a gr ....Defining mechanisms of action of novel alpha-conotoxins at nicotinic receptor-channels. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a greater understanding of how the nervous system functions. This knowledge will help in the design of new drugs to treat a variety of diseases and disorders. Essentially we will use a chemical armoury developed by the cone snail to design state-of-the-art mini-protein drugs.Read moreRead less
Particle transport in the human upper airway. This project aims to determine the fundamental mechanisms that drive particle transport in physiologically realistic human airways. Through use of novel magnetic resonance imaging and laser diagnostic techniques, the project expects to transform our ability to develop effective and validated predictive capabilities for particle transport in physiologically accurate geometries. The project outcomes are expected to enable unprecedented definition of ho ....Particle transport in the human upper airway. This project aims to determine the fundamental mechanisms that drive particle transport in physiologically realistic human airways. Through use of novel magnetic resonance imaging and laser diagnostic techniques, the project expects to transform our ability to develop effective and validated predictive capabilities for particle transport in physiologically accurate geometries. The project outcomes are expected to enable unprecedented definition of how particles are transported in human airways as a function of breathing profiles, particle properties and morphology.Read moreRead less
Enabling aerosol delivery of phages to defeat antibiotic-resistant bacteria. This project aims to explore the use of bacteriophages towards producing a safe, natural, and highly effective alternative to traditional antibiotics. Respiratory infections caused by multidrug-resistant Gram-negative bacteria are a major health problem worldwide, and cost Australia over $150 million annually. Some 5,000 Australians die each year from antibiotic resistant infections. The project aims to produce efficac ....Enabling aerosol delivery of phages to defeat antibiotic-resistant bacteria. This project aims to explore the use of bacteriophages towards producing a safe, natural, and highly effective alternative to traditional antibiotics. Respiratory infections caused by multidrug-resistant Gram-negative bacteria are a major health problem worldwide, and cost Australia over $150 million annually. Some 5,000 Australians die each year from antibiotic resistant infections. The project aims to produce efficacious and stable formulations of bacteriophages for easy delivery by inhalation as aerosols with a long shelf-life, making them a commercially viable product. The expected research outcome can lead to an economic and efficient technology to produce phage powders for novel treatment strategies of infections by inhalation.Read moreRead less