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
Differential Isotope Proteome Mapping of Transforming Growth Factor Beta Cell Signalling. Our research will capitalise on Australia's expertise and prior infrastructure investments in frontier, proteomic technologies to elucidate novel intracellular signalling pathways that contribute to the development of cancer. New approaches will be developed using isotopes to provide sensitive and accurate measurements of changes in protein expression levels. This technology will allow us to define complex ....Differential Isotope Proteome Mapping of Transforming Growth Factor Beta Cell Signalling. Our research will capitalise on Australia's expertise and prior infrastructure investments in frontier, proteomic technologies to elucidate novel intracellular signalling pathways that contribute to the development of cancer. New approaches will be developed using isotopes to provide sensitive and accurate measurements of changes in protein expression levels. This technology will allow us to define complex intracellular signalling networks. This is an important step towards identifying new drug targets that are responsible for tumour growth. Australian science will benefit from the training of new scientists in modern, post-genome technologies where there is currently a world shortage of experienced personnel.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
Molecular Mechanisms of Biochemical Regulation: Neutron and X-ray Scattering Studies. This project will develop and use novel neutron and x-ray scattering methods to study the molecular mechanisms by which nature regulates biochemical processes. Healthy function requires cells to tightly control and coordinate a myriad of molecular activities. My research focuses on a set of interdependent molecular networks inside cells whose behavior is controlled by the so-called 'second messengers' that tr ....Molecular Mechanisms of Biochemical Regulation: Neutron and X-ray Scattering Studies. This project will develop and use novel neutron and x-ray scattering methods to study the molecular mechanisms by which nature regulates biochemical processes. Healthy function requires cells to tightly control and coordinate a myriad of molecular activities. My research focuses on a set of interdependent molecular networks inside cells whose behavior is controlled by the so-called 'second messengers' that translate external signals into the right cellular responses. The proposed experiments will provide a unique structural framework by which we can understand how these signals are transmitted. Such knowledge is an important foundation for advances in biomedical research and biotechnology applications.Read moreRead less
Molecular mechanisms of two-component signal transduction in bacteria. The focus of this research is on the protein complexes that transmit signals in bacteria to elicit the desired responses to environmental stimuli. Like many dynamic processes in cells, signaling requires proteins that are flexible and hence resistant to high-resolution structural analysis using crystallography. We will make use of new research infrastructure at the Australian synchrotron and OPAL research reactor to overcom ....Molecular mechanisms of two-component signal transduction in bacteria. The focus of this research is on the protein complexes that transmit signals in bacteria to elicit the desired responses to environmental stimuli. Like many dynamic processes in cells, signaling requires proteins that are flexible and hence resistant to high-resolution structural analysis using crystallography. We will make use of new research infrastructure at the Australian synchrotron and OPAL research reactor to overcome the challenges of flexibility in these systems. The proteins we will study are not found in humans, and hence our research will provide important structural data on potential targets for the design of novel antibiotics to fight bacterial infection.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882855
Funder
Australian Research Council
Funding Amount
$900,000.00
Summary
High-resolution imaging of live cells and tissue. Understanding the machinery of life and developing technologies that support life's processes requires biological and physical scientists and engineers to monitor molecular events in living systems. The aim is to take advantage of very recent developments in light microscopy to enable the non-invasive imaging of live cells and tissue at a previously unreachable level of detail. The instruments will form the nucleus of a new imaging facility. Sign ....High-resolution imaging of live cells and tissue. Understanding the machinery of life and developing technologies that support life's processes requires biological and physical scientists and engineers to monitor molecular events in living systems. The aim is to take advantage of very recent developments in light microscopy to enable the non-invasive imaging of live cells and tissue at a previously unreachable level of detail. The instruments will form the nucleus of a new imaging facility. Significant advances in research areas including vascular research, cancer, immunology, cell and molecular biology, functional genomics, biotechnology, nanotechnology and material engineering will be of major benefit both nationally and globally.Read moreRead less
O-GlcNAc-phosphorylation: a novel post-translational modification regulating vesicle recycling. We will determine a biological role for our discovery of a hybrid protein modification (both carbohydrate and phosphate) on a brain protein that is involved in nerve cell communication. If this modification is more widespread, then we will have discovered a new level of cellular regulation. This discovery is likely to have a broad benefit. It will advance the understanding of carbohydrate and phosphat ....O-GlcNAc-phosphorylation: a novel post-translational modification regulating vesicle recycling. We will determine a biological role for our discovery of a hybrid protein modification (both carbohydrate and phosphate) on a brain protein that is involved in nerve cell communication. If this modification is more widespread, then we will have discovered a new level of cellular regulation. This discovery is likely to have a broad benefit. It will advance the understanding of carbohydrate and phosphate modified proteins. For example, there may be consequences for the model of hyperphosphorylated and carbohydrate modified proteins involved in neurodegeneration. There will also be a targeted benefit. An improved understanding of the mechanism of neurotransmission will benefit in designing compounds to fight diseases of neurotransmission.Read moreRead less
The Design of New Integrase Inhibitors Targeting HIV-1. There is still no cure in sight for the worldwide HIV pandemic and the worsening viral resistance problem creates a need to find new and novel compounds for therapeutic use. This project aims to design and synthesize new anti-HIV drugs by targeting two separate enzymes within the HIV life-cycle. This 'dual-action' approach of designing a single molecular scaffold to target separate enzymes would enable a synergistic effect while minimizing ....The Design of New Integrase Inhibitors Targeting HIV-1. There is still no cure in sight for the worldwide HIV pandemic and the worsening viral resistance problem creates a need to find new and novel compounds for therapeutic use. This project aims to design and synthesize new anti-HIV drugs by targeting two separate enzymes within the HIV life-cycle. This 'dual-action' approach of designing a single molecular scaffold to target separate enzymes would enable a synergistic effect while minimizing development costs. The expected outcomes from this medicinal chemistry project include the discovery of new compounds with the potential for further development as therapeutic agents against HIV.Read moreRead less
Synthetic derivatives of capsaicin and gingerols as analgesics acting at the vanilloid receptor. This project aims to prepare alpha-hydroxyketones and gingerol derivatives acting at vanilloid (VR1) receptor with potential analgesic activity. These compounds will be tested for their ability to activate the VR1 receptor, desensitize the receptor and release neuropeptides associated with pain pathways. The development of these novel compounds will contribute towards understanding the mechanisms of ....Synthetic derivatives of capsaicin and gingerols as analgesics acting at the vanilloid receptor. This project aims to prepare alpha-hydroxyketones and gingerol derivatives acting at vanilloid (VR1) receptor with potential analgesic activity. These compounds will be tested for their ability to activate the VR1 receptor, desensitize the receptor and release neuropeptides associated with pain pathways. The development of these novel compounds will contribute towards understanding the mechanisms of VR1 receptor activation and provide information on how the VR1 receptor is regulated. We will determine and compare neurotoxicity of these compounds to capsaicin which is known to possess neurotoxic activity. The outcome of this project may result in effective agents for better pain management.
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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