Discovery Early Career Researcher Award - Grant ID: DE120101550
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Understanding multidrug resistance: identifying the molecular basis of substrate and inhibitor transport by P-glycoprotein. Chemotherapy resistance causes 90 per cent of cancer deaths and is commonly triggered by the increased activity of P-glycoprotein, which controls the cellular clearance of drugs. This project will determine how P-glycoprotein recognises and transports drugs, essential knowledge for the design of anticancer agents that can stop chemotherapy resistance.
Evolution of halophytes: a phyloinformatic approach to understanding and exploiting the traits underlying salt-tolerance in plants. Salinity is an increasing burden on the Australian economy & environment, with >2 million ha of salt-affected land, at an annual cost to agriculture over $187 million. One solution is to exploit naturally salt-tolerant plants to increase productive agricultural land and restore salt-affected environments. To do this, we must increase basic knowledge of the diversity ....Evolution of halophytes: a phyloinformatic approach to understanding and exploiting the traits underlying salt-tolerance in plants. Salinity is an increasing burden on the Australian economy & environment, with >2 million ha of salt-affected land, at an annual cost to agriculture over $187 million. One solution is to exploit naturally salt-tolerant plants to increase productive agricultural land and restore salt-affected environments. To do this, we must increase basic knowledge of the diversity & distribution of salt-tolerance. This project is the first to use DNA sequences from thousands of species to understand the evolution of salt-tolerance in order to provide the foundation for the development of new crop varieties, selection of species that can be developed for bioremediation, and identification of traits that will be profitable targets for breeding programs. Read moreRead less
Gain from pain: new tools from venomous animals for exploring pain pathways. This project aims to explore animal venoms for new pain-causing toxins, to determine their structure and mechanism of action. Many venomous animals use their venom defensively and envenomation is frequently associated with rapid and often excruciating pain. In most cases the molecular mechanisms by which they achieve this is unknown. Using biochemical, pharmacological and biophysical techniques, this project expects to ....Gain from pain: new tools from venomous animals for exploring pain pathways. This project aims to explore animal venoms for new pain-causing toxins, to determine their structure and mechanism of action. Many venomous animals use their venom defensively and envenomation is frequently associated with rapid and often excruciating pain. In most cases the molecular mechanisms by which they achieve this is unknown. Using biochemical, pharmacological and biophysical techniques, this project expects to uncover toxins that employ new mechanisms of pain signalling, leading to new insights into pain physiology.Read moreRead less
Pharmacology Of Potential Anti-Tumour Agents: Iron Chelators Of The BpT Class
Funder
National Health and Medical Research Council
Funding Amount
$585,455.00
Summary
Pharmacology of Potential Anti-Tumour Agents: Iron Chelators of the BpT Class Cancer cells have a high iron requirement for DNA synthesis and many clinical trials showed Fe chelators are effective anti-cancer drugs. Their potential to act as anti-tumour agents has been confirmed by the entrance of Triapine into widespread NCI clinical trials. In this NHMRC Renewal, we will perform pharmacological and preclinical studies to promote the development of BpT chelators as novel anti-tumour agents.
The use of molecular sponges to inhibit small Ribonucleic acid activity in plants. The deletion of gene activity is the most powerful way to understand gene function; however for genes encoding small Ribonucleic acids (RNAs) no current methodology can efficiently achieve this. Here, we aim to develop a gene silencing technology for small RNA encoding genes, which can be utilised to determine their function and used for biotechnological applications.
Methods for Protein Structure Analysis by Electron Paramagnetic Resonance. This highly interdisciplinary project aims to establish new tools to analyse the structure and motions of proteins that are otherwise difficult to study. A combination of advanced biochemistry, modern magnetic spectroscopy methods, and high-performance computing techniques will be applied to study proteins at physiological concentrations and in complex environments. New techniques will be developed and tested on proteins ....Methods for Protein Structure Analysis by Electron Paramagnetic Resonance. This highly interdisciplinary project aims to establish new tools to analyse the structure and motions of proteins that are otherwise difficult to study. A combination of advanced biochemistry, modern magnetic spectroscopy methods, and high-performance computing techniques will be applied to study proteins at physiological concentrations and in complex environments. New techniques will be developed and tested on proteins of high biochemical or biomedical importance, and the approach will be applied to established drug targets.Read moreRead less
ARC Centre of Excellence in Synthetic Biology. The ARC Centre of Excellence in Synthetic Biology (CoESB) will provide the technical innovation critical for Australia to develop a vibrant bioeconomy building on the nation’s strengths in agriculture. For thousands of years we have used microbes to create bread, wine, cheese. Now, our Centre will pioneer new approaches to the design of synthetic microbes, enabling the development of custom-designed microbial communities, synthetic organelles and ne ....ARC Centre of Excellence in Synthetic Biology. The ARC Centre of Excellence in Synthetic Biology (CoESB) will provide the technical innovation critical for Australia to develop a vibrant bioeconomy building on the nation’s strengths in agriculture. For thousands of years we have used microbes to create bread, wine, cheese. Now, our Centre will pioneer new approaches to the design of synthetic microbes, enabling the development of custom-designed microbial communities, synthetic organelles and new to nature biological pathways and enzymes. CoESB will combine engineering with molecular biology to design and construct novel biological systems that can convert biomass from agriculture or waste streams to biofuel, bioplastics and other high-value chemicals.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
Molecular mechanisms of signalling by plant immune receptors. This project aims to understand how resistance proteins function and to find new sources of these proteins. Plant diseases account for 15% loss of global crop production, representing a threat to food security. Fungicides, one key form of protection, represent environmental concerns. The other key form of protection corresponds to resistance gene breeding, which is limited by lengthy breeding processes, restricted choice of genes from ....Molecular mechanisms of signalling by plant immune receptors. This project aims to understand how resistance proteins function and to find new sources of these proteins. Plant diseases account for 15% loss of global crop production, representing a threat to food security. Fungicides, one key form of protection, represent environmental concerns. The other key form of protection corresponds to resistance gene breeding, which is limited by lengthy breeding processes, restricted choice of genes from sexually compatible species and short effective time spans in the field. Building on previous research, this project aims to characterise the molecular basis of the Toll/interleukin-1 receptor domain-mediated nicotinamide adenine dinucleotide (NAD+) cleavage and the structural architecture of plant NLR complexes. This knowledge will support the long-term objective of protecting crops from pathogens.Read moreRead less
Understanding the molecular function of plant disease resistance proteins, pathogen effectors and their interaction to protect Australian agriculture. This project aims to understand the processes that enable resistant plants to detect and respond to pathogen attack. The acquired knowledge will form the foundation for durable plant disease resistance measures that can be applied to a wide range of crop diseases in an environmentally sustainable manner.