Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100157
Funder
Australian Research Council
Funding Amount
$600,000.00
Summary
Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information th ....Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information that is not easily obtainable with other approaches. The project will enable Australian researchers to image and analyse the full complexity of biological systems, potentially transforming cell biology, drug development and understanding the molecular basis of disease. It will also demonstrate how the capacity of microscopy facilities can be enhanced and bias in imaging data reduced by automating data acquisition and mining of image-based data.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0237729
Funder
Australian Research Council
Funding Amount
$735,000.00
Summary
A proteomics facility for Queensland researchers. The successful completion of sequencing of the genomes of many organisms, including man, has thrown emphasis back on the identification of proteins involved in the complex events that sustain cellular life. Our aim is to set up a world-class facility for proteomics research which will allow a large cohort of scientists at several institutions to identify individual proteins in vanishingly small samples of very complex mixtures. This facility wi ....A proteomics facility for Queensland researchers. The successful completion of sequencing of the genomes of many organisms, including man, has thrown emphasis back on the identification of proteins involved in the complex events that sustain cellular life. Our aim is to set up a world-class facility for proteomics research which will allow a large cohort of scientists at several institutions to identify individual proteins in vanishingly small samples of very complex mixtures. This facility will enable investigation of the control of gene expression, the intricate organisation of proteins within cells, and proteins which are potential drug targets. This equipment is an essential resource for Queensland research groups.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0454052
Funder
Australian Research Council
Funding Amount
$733,595.00
Summary
Tandem Matrix-Assisted Laser Desorption/Ionisation Time-Of-Flight Mass Spectrometer and Robots for High Throughput Proteomics Analysis. This proposal seeks to establish the capacity to perform high-energy tandem mass spectrometry on a high throughput basis, through purchase and coordinated operation of a Matrix-Assisted Laser Desorption/Ionisation - Time of Flight / Time of Flight - Mass Spectrometer and ancillary equipment, to enhance the proteomics expertise, infrastructure and research plans ....Tandem Matrix-Assisted Laser Desorption/Ionisation Time-Of-Flight Mass Spectrometer and Robots for High Throughput Proteomics Analysis. This proposal seeks to establish the capacity to perform high-energy tandem mass spectrometry on a high throughput basis, through purchase and coordinated operation of a Matrix-Assisted Laser Desorption/Ionisation - Time of Flight / Time of Flight - Mass Spectrometer and ancillary equipment, to enhance the proteomics expertise, infrastructure and research plans of a network of institutions from Queensland and New South Wales and their collaborators. Access to such instrumentation is critical to high level achievement in proteomics, a key platform technology for National Research Priorities relating to Frontier Technologies. No comparable instrument currently exists in Australia.Read moreRead less
Examination Of The Molecular Pharmacology Of Anthracyclines Induced Via Their Interaction With Iron
Funder
National Health and Medical Research Council
Funding Amount
$618,401.00
Summary
Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and ....Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and haem synthesis. Hence, this effect probably contributes to the cytotoxic activity of anthracyclines on the heart. We showed that novel drugs developed in my lab that bind Fe called chelators show high activity in animals (DR4) and prevent anthracycline-mediated Fe accumulation in ferritin. Importantly, Fe chelators have been shown to inhibit anthracycline-mediated cardiotoxicity. Indeed, the clinically used cardioprotective agent, ICRF-187, is actually an Fe chelator (5, DR6). However, ICRF-187 is not totally successful in terms of its cardioprotective effects and can cause myelosuppression (5, DR6). While the clinically used chelator, desferrioxamine (DFO), can prevent anthracycline-mediated cardiotoxicity, its poor membrane permeability limits its effectiveness. Our chelators are highly permeable and overcome the disadvantages of DFO (DR4). Thus, they are vital to examine for preventing anthracycline-mediated cardiotoxicity. In this proposal we will examine the changes in Fe metabolism induced by anthracyclines and test the hypothesis that novel Fe chelators may prevent the cardiotoxicity of these agents. We also aim to be the first to assess if preparation of anthracyclines which cannot bind iron prevents their cardiotoxicity. This will be done by preparing metal complexes of these drugs which prevent Fe-binding eg. anthracycline-zinc complexes. These studies are important for the development of less cardiotoxic forms of these very useful anti-tumour agents.Read moreRead less
Protein biosensors for detecting smoke exposure of grapes. Bush fires and controlled burns that take place in the vicinity of vineyards can lead to grape contamination with tasteless phenolic glucosides. Their hydrolysis during wine making leads to “smoke taint” – an unpleasant medicinal taste that can render wine undrinkable. We will apply a combination of organic synthesis, protein engineering and directed evolution to develop protein-based biosensors of phenolic glucosides. These biosensors w ....Protein biosensors for detecting smoke exposure of grapes. Bush fires and controlled burns that take place in the vicinity of vineyards can lead to grape contamination with tasteless phenolic glucosides. Their hydrolysis during wine making leads to “smoke taint” – an unpleasant medicinal taste that can render wine undrinkable. We will apply a combination of organic synthesis, protein engineering and directed evolution to develop protein-based biosensors of phenolic glucosides. These biosensors will be used to devise a simple portable colorimetric test that can be performed in the vineyard or the winery. The ability to rapidly determine the level of grape contamination with phenolic glucosides would give Australian wine growers and wine makers a powerful tool to mitigate the effects of bushfires.Read moreRead less
Industrial Transformation Training Centres - Grant ID: IC210100047
Funder
Australian Research Council
Funding Amount
$5,000,000.00
Summary
ARC Training Centre for Accelerated Future Crop Development . The Centre will create a new generation of leaders in the implementation of advanced gene and field technologies for the benefit of the Australian agriculture industry. We will build the workforce and foundations that will drive translation of breakthroughs in advanced breeding, phenotyping and genetic technologies into higher-yielding crops. This will increase productivity across the sector and create new markets. Our technical trai ....ARC Training Centre for Accelerated Future Crop Development . The Centre will create a new generation of leaders in the implementation of advanced gene and field technologies for the benefit of the Australian agriculture industry. We will build the workforce and foundations that will drive translation of breakthroughs in advanced breeding, phenotyping and genetic technologies into higher-yielding crops. This will increase productivity across the sector and create new markets. Our technical training programs for graduates, trainees and industry will interface with best evidence-based practices in the wider socio-economic, regulatory and environmental contexts. Coupled with community and stakeholder engagement, the Centre will redefine and secure Australia’s future in agriculture. Read moreRead less
Protein Structure and Dynamics by Electron/Nuclear Paramagnetic Resonance. This interdisciplinary project aims to establish new magnetic resonance methods for the analysis of protein structure and motion at low concentrations and in physiological conditions that are otherwise difficult or impossible to study. It brings together four different research groups with expertise in advanced biochemistry, modern magnetic spectroscopy and high-performance computing. The project expects to develop tools ....Protein Structure and Dynamics by Electron/Nuclear Paramagnetic Resonance. This interdisciplinary project aims to establish new magnetic resonance methods for the analysis of protein structure and motion at low concentrations and in physiological conditions that are otherwise difficult or impossible to study. It brings together four different research groups with expertise in advanced biochemistry, modern magnetic spectroscopy and high-performance computing. The project expects to develop tools to study protein structure, protein-protein association and protein-ligand interactions of established drug-targets. Expected outcomes include new techniques that quickly inform how drugs work, providing significant benefits to many researchers studying biomolecules, and supporting Australia’s growing biotechnology sector. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE170100021
Funder
Australian Research Council
Funding Amount
$2,168,000.00
Summary
Australian Metabolic Phenotyping Centre (AMPC). This project aims to establish a centre for targeted and exploratory metabolic phenotyping. Metabolic phenotyping quantitatively measures the precursors, intermediates and products of metabolism interacting within a biological system. This project will use high-resolution spectrometry and spectroscopy to generate comprehensive, multi-parameter metabolite data sets for biological samples at the population level, at unprecedented throughput and low c ....Australian Metabolic Phenotyping Centre (AMPC). This project aims to establish a centre for targeted and exploratory metabolic phenotyping. Metabolic phenotyping quantitatively measures the precursors, intermediates and products of metabolism interacting within a biological system. This project will use high-resolution spectrometry and spectroscopy to generate comprehensive, multi-parameter metabolite data sets for biological samples at the population level, at unprecedented throughput and low cost, to address biological and biomedical research needs. This project is expected to make Australian scientists globally competitive in the life sciences including biological, clinical and biomedical, plant and crop sciences, analytical chemistry, toxicology, agriculture, wildlife conservation and sports science, and to drive advances in the data sciences for systems biology.Read moreRead less
Selectively targeting cancer and infectious disease with fragment-based drug discovery. Finding better compounds as starting points is one of the major challenges for drug discovery research. Fragments are small, weak binding molecules that can be upsized into drug leads with better properties when compared to starting with larger molecules. This project addresses two weaknesses of current fragment based drug discovery (FBDD) methods: first, the limitations associated with screening fragments; a ....Selectively targeting cancer and infectious disease with fragment-based drug discovery. Finding better compounds as starting points is one of the major challenges for drug discovery research. Fragments are small, weak binding molecules that can be upsized into drug leads with better properties when compared to starting with larger molecules. This project addresses two weaknesses of current fragment based drug discovery (FBDD) methods: first, the limitations associated with screening fragments; and second, the quality of commercial fragment libraries. This project anticipates that the findings will establish a commanding role for both mass spectrometry and three-dimensional fragments in advancing FBDD approaches. It also expects to identify fragments with favourable development prospects towards the next generation of therapeutics.Read moreRead less