The combined use of proteomics and small molecules for target identification and pathway analysis. This project intends to investigate how a series of new small molecules identified from our research to improve the metabolic effects of insulin. This project will integrate medicinal chemistry with proteomics and metabolic biology to identify the cellular targets and their mechanism of action.
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
Cytorefractometry - a new technique for refractive index tomography of living cells. An ultrahigh-resolution bifocal optical coherence refractometry is proposed, and will result to micron-scale-resolution refractive index tomography of living cells, termed cytorefractometry. This technique represents an extension from bifocal optical coherence refractometry that has recently shown a remarkable promise for direct, several-frames-per-second, motion-artifact-free determination of refractive index ....Cytorefractometry - a new technique for refractive index tomography of living cells. An ultrahigh-resolution bifocal optical coherence refractometry is proposed, and will result to micron-scale-resolution refractive index tomography of living cells, termed cytorefractometry. This technique represents an extension from bifocal optical coherence refractometry that has recently shown a remarkable promise for direct, several-frames-per-second, motion-artifact-free determination of refractive index in turbid media, including biological tissue in vivo. We propose to apply our novel technique to study tissue calcification, a serious problem in cardiology, by making use of the refractive index contrast mechanism. Calcification of smooth muscle cells and aorta subdermal implant models will be studied aiming for prevention of calcification-associated pathologies.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
Binary regression with additive predictors: new statistical theory with healthcare applications. This project will develop new statistical analysis techniques for predicting whether someone is at risk of adverse health outcomes. The project will then apply the new techniques to a large database on heart attacks, leading to new insights into how patient characteristics and treatments affect the chance of dying from a heart attack.
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
Microwave Differential Imaging of Myocardium for Assessment and Therapeutic Monitoring of Transcatheter Cardiac Ablation. We propose to develop Microwave Imaging techniques for cardiovascular disease diagnosis at 2.45 GHz. Firstly, we aim to image the contrast in the complex dielectric constants of healthy and ischaemic heart tissue. The second aim is to image the extent and efficacy of therapeutic lesion formation due to cardiac ablation modalities. We propose to develop a cylindrical antenna ....Microwave Differential Imaging of Myocardium for Assessment and Therapeutic Monitoring of Transcatheter Cardiac Ablation. We propose to develop Microwave Imaging techniques for cardiovascular disease diagnosis at 2.45 GHz. Firstly, we aim to image the contrast in the complex dielectric constants of healthy and ischaemic heart tissue. The second aim is to image the extent and efficacy of therapeutic lesion formation due to cardiac ablation modalities. We propose to develop a cylindrical antenna array for near field microwave imaging using novel wire antenna elements. Fast and iterative reconstruction algorithms based on electromagnetic scattering and computational techniques will also be developed.Read moreRead less