Probing Anaesthetic Effects with New Functional Imaging Paradigms. This project seeks new insights into the effects of anaesthetics on brain function and repair. Anaesthesia is used in small-animal imaging to immobilise the animal, but in many cases the anaesthesia itself affects the neurophysiological parameters under study. It has also been shown that many anaesthetics enhance recovery after brain injury in small animals. This project plans to exploit a novel functional brain-imaging technique ....Probing Anaesthetic Effects with New Functional Imaging Paradigms. This project seeks new insights into the effects of anaesthetics on brain function and repair. Anaesthesia is used in small-animal imaging to immobilise the animal, but in many cases the anaesthesia itself affects the neurophysiological parameters under study. It has also been shown that many anaesthetics enhance recovery after brain injury in small animals. This project plans to exploit a novel functional brain-imaging technique for conscious animals to gain new insights into the effects of anaesthetics on brain function and recovery from injury. The knowledge gained is expected to improve knowledge of anaesthetic action, guide future anaesthetic use in small animal imaging to improve the accuracy of image-derived research data, and help to clarify how anaesthetics confer neuroprotective effects in brain injury.Read moreRead less
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.
Development of prodrug strategies for achieving increased penetration and selective activation in solid tumours. A primary cause of cancer deaths is relapse following treatment resulting from the drug failing to penetrate and destroy all parts of the tumour. The project aims to develop anticancer agents that are better able to reach all parts of the tumour and have toxicities low enough to enable sufficient doses to be used to kill all cancer cells.
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
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
Synthetic Endonucleases: Novel DNA Cleaving Agents for Cancer Chemotherapy. Cancer is a common disease in our society, with more than 1 in 4 of us dieing from it. The current survival rate is 50%, and has been so for the past 5 decades. Thus, there is clearly an urgent need for better forms of therapy. Chemotherapy is the mainstay of treatment once the disease has spread from its original site. The National Benefits from the development of a new class of effective cancer drug are two-fold. Firs ....Synthetic Endonucleases: Novel DNA Cleaving Agents for Cancer Chemotherapy. Cancer is a common disease in our society, with more than 1 in 4 of us dieing from it. The current survival rate is 50%, and has been so for the past 5 decades. Thus, there is clearly an urgent need for better forms of therapy. Chemotherapy is the mainstay of treatment once the disease has spread from its original site. The National Benefits from the development of a new class of effective cancer drug are two-fold. Firstly, much relief will come to people suffering from cancer, as some will live longer, and some will be cured. Secondly, the economic benefits are extensive, since the world market in cancer drugs is measured in billions $US, and significant monies will flow to those who hold the intellectual property rights. Read moreRead less
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
Profiling tissue protein, elemental ions and nanoparticle distributions. This project aims to investigate protein-protein interactions that are crucial to homeostatic cell signalling and viability in a changing tissue environment. The central goal is to develop and validate protocols to combine cutting-edge tissue imaging modalities to map and characterise tissue distributions of native and modified proteins, elemental ions and pharmacological agents including nanoparticles and nanovehicles. The ....Profiling tissue protein, elemental ions and nanoparticle distributions. This project aims to investigate protein-protein interactions that are crucial to homeostatic cell signalling and viability in a changing tissue environment. The central goal is to develop and validate protocols to combine cutting-edge tissue imaging modalities to map and characterise tissue distributions of native and modified proteins, elemental ions and pharmacological agents including nanoparticles and nanovehicles. The aim is to use novel tissue scanning mass spectrometry techniques in conjunction with X-ray-based microprobe spectroscopy and advanced multi-parameter cytometry to identify spatial distributions of proteins, ions and drugs in tissues. This approach may provide new information about the maintenance of homeostatic control and the content, distribution and potential metabolism of drugs or nanoparticles within biological tissues.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