Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100125
Funder
Australian Research Council
Funding Amount
$330,000.00
Summary
Oxidative stress bioanalytical facility. The primary national benefit of this application is that it will provide a currently unavailable, state-of-the-art facility for Australian scientists to define precisely how changes in cellular redox state contribute to biological processes relevant to health and diseases. The facility will uniquely complement, and in many cases integrate with existing facilities in this area of research in Australia. It will act as a platform for major national and inter ....Oxidative stress bioanalytical facility. The primary national benefit of this application is that it will provide a currently unavailable, state-of-the-art facility for Australian scientists to define precisely how changes in cellular redox state contribute to biological processes relevant to health and diseases. The facility will uniquely complement, and in many cases integrate with existing facilities in this area of research in Australia. It will act as a platform for major national and international research collaborations, develop cutting-edge technology and unique local skills, and contribute to Australia maintaining a leading position in redox-related research in biology and medicine. In doing so, the facility will increase the likelihood of gaining future, value-adding funding.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
Is transport of miRNAs essential for plant development? This project will provide knowledge of how a new class of biologically active molecule (micro RNA) regulates expression of genes at sites in the plant that are critical for growth and development. MicroRNAs are believed to influence the size and shape of plants, how rapidly they grow and how well they produce and fill seeds. These molecules are part of a group of bioactive signals that move throughout the plant, functioning like hormones bu ....Is transport of miRNAs essential for plant development? This project will provide knowledge of how a new class of biologically active molecule (micro RNA) regulates expression of genes at sites in the plant that are critical for growth and development. MicroRNAs are believed to influence the size and shape of plants, how rapidly they grow and how well they produce and fill seeds. These molecules are part of a group of bioactive signals that move throughout the plant, functioning like hormones but directly influencing how well critical genes work. Their exploitation holds great promise for manipulating plant performance and enhancing crop yields. 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
Special Research Initiatives - Grant ID: SR1101002
Funder
Australian Research Council
Funding Amount
$21,000,000.00
Summary
Stem Cells Australia. Despite progress in stem cell research, scientists do not understand how stem cells “decide” what to become. Stem Cells Australia will draw upon strengths within Australia’s premier stem cell research universities and institutes. This collaboration between leading bioengineering, nanotechnology, stem cell and advanced molecular analysis experts, will fast-track efforts to deliver a fundamental understanding of the mechanisms of stem cell regulation and differentiation, and ....Stem Cells Australia. Despite progress in stem cell research, scientists do not understand how stem cells “decide” what to become. Stem Cells Australia will draw upon strengths within Australia’s premier stem cell research universities and institutes. This collaboration between leading bioengineering, nanotechnology, stem cell and advanced molecular analysis experts, will fast-track efforts to deliver a fundamental understanding of the mechanisms of stem cell regulation and differentiation, and the ability to control and influence this process. Stem Cells Australia will deliver new methods for stem cell propagation and manipulation, new translational technologies for therapeutic applications, and will prepare Australia’s future stem cell scientific leaders.Read moreRead less
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
Genome Approaches to Investigate Metabolic Coordination in Plant Cells. Metabolism of C and N in legume nodules requires interaction between the symbiotic bacteria and plant organelles, particularly metabolism in plastids and mitochondria. Fixed N is assimilated through the de novo synthesis of purines in both plastids and mitochondria. However, each of the nine pathway enzymes is encoded by a single gene, indicating each protein is targeted to both organelles. Purine metabolism will provide ....Genome Approaches to Investigate Metabolic Coordination in Plant Cells. Metabolism of C and N in legume nodules requires interaction between the symbiotic bacteria and plant organelles, particularly metabolism in plastids and mitochondria. Fixed N is assimilated through the de novo synthesis of purines in both plastids and mitochondria. However, each of the nine pathway enzymes is encoded by a single gene, indicating each protein is targeted to both organelles. Purine metabolism will provide a model to assess the more general occurrence of dual-targeted proteins in plants. The aim is to identify and eventually exploit the signalling mechanism(s) that mediate communication between plastids and mitochondria.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0346892
Funder
Australian Research Council
Funding Amount
$689,000.00
Summary
Protein Over-Expression/Purification and Macromolecular Structure Determination by X-Ray Diffraction. This proposal seeks funds for state-of-the-art facilities for protein over-expression and macromolecular X-ray diffraction. This will build upon recent initiatives within the collaborating institutions in the field of Structural Biology. It will enable research groups in Perth to pursue the large-scale production of important proteins and to conduct high-resolution structural studies using X-ray ....Protein Over-Expression/Purification and Macromolecular Structure Determination by X-Ray Diffraction. This proposal seeks funds for state-of-the-art facilities for protein over-expression and macromolecular X-ray diffraction. This will build upon recent initiatives within the collaborating institutions in the field of Structural Biology. It will enable research groups in Perth to pursue the large-scale production of important proteins and to conduct high-resolution structural studies using X-ray crystallographic techniques. This technology, which is one of the most important tools in modern biology, provides unique insights into the chemical mechanisms of biological macromolecules and will significantly enhance a great breadth of biological research in Western Australia.Read moreRead less
Targeting the undruggable: epitope mapping using Phylomers peptides to modulate activity of Transcription Factors. This project aims at expanding the pool of drug targets, by extending drug screening to protein-protein interaction networks. This project aims to assemble a novel technical platform to detect binding between proteins, using a combination of cell-free protein expression, AlphaScreen and single-molecule fluorescence. This pipeline has great potential to accelerate the exploration of ....Targeting the undruggable: epitope mapping using Phylomers peptides to modulate activity of Transcription Factors. This project aims at expanding the pool of drug targets, by extending drug screening to protein-protein interaction networks. This project aims to assemble a novel technical platform to detect binding between proteins, using a combination of cell-free protein expression, AlphaScreen and single-molecule fluorescence. This pipeline has great potential to accelerate the exploration of protein networks, and provides also a generic platform for drug screening on difficult targets. The project intends to screen Phylogica's libraries of peptides called Phylomers to discover tight binders to a Transcription Factor, Sox18. The objective of this project is to determine which Phylomers can disrupt specific interactions between Sox18 and its binding partners involved in lymphangiogenesis.Read moreRead less
A microfluidic array of phylomers for rapid discovery of peptide probes and biomarkers. This project, through an alliance with Phylogica, aims at exploiting a unique source of structural diversity for drug discovery, harvesting the creativity of nature in its most exotic places. The project will develop a novel approach to validate design and validate drug candidates, by gathering them on a single screening chip for a powerful discovery platform.