Mechanisms maintaining mitochondrial copper homeostasis. This project aims to define the molecular mechanisms by which copper is trafficked and balanced within mitochondria. The project will employ an integrated biological, biochemical, biophysical and structural approach to examine the proteins which underpin the balance between the essentiality for copper and its toxicity, within this organelle. This project will deliver fundamental insights into how mitochondria contribute to and achieve cell ....Mechanisms maintaining mitochondrial copper homeostasis. This project aims to define the molecular mechanisms by which copper is trafficked and balanced within mitochondria. The project will employ an integrated biological, biochemical, biophysical and structural approach to examine the proteins which underpin the balance between the essentiality for copper and its toxicity, within this organelle. This project will deliver fundamental insights into how mitochondria contribute to and achieve cellular metal homeostasis, in addition to molecular explanations for how faults in this process result in mitochondrial defects. Major benefits include research training, strengthened international linkages and fundamental insights into mitochondrial biochemistry.Read moreRead less
Genetic code expansion of a eukaryotic in vitro translation system. The genetic code programs biosynthesis of polypeptides with efficiency vastly superior to chemical engineering. As the chemical diversity of natural amino acids in proteins is limited, finding ways to include “unnatural” amino acids can supercharge biology with a range of new protein activities. While the genetic code can be expanded to make space for unnatural amino acids, the rarity of free codons and reliance on prokaryotic ....Genetic code expansion of a eukaryotic in vitro translation system. The genetic code programs biosynthesis of polypeptides with efficiency vastly superior to chemical engineering. As the chemical diversity of natural amino acids in proteins is limited, finding ways to include “unnatural” amino acids can supercharge biology with a range of new protein activities. While the genetic code can be expanded to make space for unnatural amino acids, the rarity of free codons and reliance on prokaryotic organisms limit the applicability of this approach. We will develop a new higher-organism cell-free protein production system that can incorporate multiple unnatural amino acids into defined points of proteins. This, enabling and broadly applicable technology, will be tested by constructing opioid biosensors.Read moreRead less
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
Biologically inert probes to unravel nutrient directed cellular processing . In this project we will develop novel compounds that can act as probes of the pathways present in cells for the uptake of nutrients and other essential molecules and show how to generate new agents for identifying and targeting specific populations of cells. The project will generate new tools for understanding biological processes including cell transport and processing. The insights gained from this work are expected ....Biologically inert probes to unravel nutrient directed cellular processing . In this project we will develop novel compounds that can act as probes of the pathways present in cells for the uptake of nutrients and other essential molecules and show how to generate new agents for identifying and targeting specific populations of cells. The project will generate new tools for understanding biological processes including cell transport and processing. The insights gained from this work are expected to help guide the development of new agents for selectively delivering imaging and biologically active agents to cells.Read moreRead less
Reverse chemical proteomics: harnessing yeast display for drug discovery. This project aims to develop a technique that can rapidly identify the cellular protein targets of biologically active natural products. This project expects to provide fundamental biological and chemical insights into Australia's unique biodiversity that will facilitate the development of new therapeutic agents and agrochemicals based on leads provided by Nature. Expected outcomes of this project include an optimised and ....Reverse chemical proteomics: harnessing yeast display for drug discovery. This project aims to develop a technique that can rapidly identify the cellular protein targets of biologically active natural products. This project expects to provide fundamental biological and chemical insights into Australia's unique biodiversity that will facilitate the development of new therapeutic agents and agrochemicals based on leads provided by Nature. Expected outcomes of this project include an optimised and validated platform technology for accelerating drug discovery and development. This should substantially reduce the costs associated with fighting human and animal diseases, leading to improved health, productivity and quality of life.Read moreRead less
Glycan-based prebiotic approaches to increase food safety in Australia. Since the launch of the first Australian Animal Sector National Antimicrobial Resistance Plan (2018) several approaches have been suggested to reduce the use antibiotics in agriculture, however no alternatives to antibiotics have been suggested or trialled. In this proposal we aim to develop a novel glycan-based prebiotic strategy to reduce Campylobacter jejuni colonisation in chicken and poultry by disrupting important glyc ....Glycan-based prebiotic approaches to increase food safety in Australia. Since the launch of the first Australian Animal Sector National Antimicrobial Resistance Plan (2018) several approaches have been suggested to reduce the use antibiotics in agriculture, however no alternatives to antibiotics have been suggested or trialled. In this proposal we aim to develop a novel glycan-based prebiotic strategy to reduce Campylobacter jejuni colonisation in chicken and poultry by disrupting important glycan-glycan interactions. Outcomes of this proposal is a cost-effective antibiotic- and vaccine-independent animal feed supplement strategy that will decrease the risk of human food-borne illness and therefore promoting food safety and public health in Australia. Read moreRead less
Molecular mechanisms of mechanosensation and shape regulation in cells. This project aims to explore how cells physically sense and respond to the surrounding environment on a molecular level. Physical distortion of erythrocytes doubles their glucose consumption and increases cation membrane flux five-fold. This mechanism involves opening of the mechanosenstive ion channel Piezo1. This project will include a kinetic description of these phenomena, with a goal to establish a predictive mathematic ....Molecular mechanisms of mechanosensation and shape regulation in cells. This project aims to explore how cells physically sense and respond to the surrounding environment on a molecular level. Physical distortion of erythrocytes doubles their glucose consumption and increases cation membrane flux five-fold. This mechanism involves opening of the mechanosenstive ion channel Piezo1. This project will include a kinetic description of these phenomena, with a goal to establish a predictive mathematical model of the regulation of cell-shape and volume. The project will provide an understanding of mechanisms operating when cells and tissues are succumbing to trauma and invasion, and how to control these processes on a molecular level.Read moreRead less
A novel platform for the biosynthesis of commercially valuable saxitoxins. Saxitoxins are potent microbial toxins, which pose a significant threat to food and water quality. Highly pure saxitoxins are required for environmental monitoring and studies of cell physiology. Certain analogues have also shown promise as long-lasting and non-addictive pain blockers. However, the procurement of these compounds from natural sources is convoluted and unsustainable. This project aims to use the latest synt ....A novel platform for the biosynthesis of commercially valuable saxitoxins. Saxitoxins are potent microbial toxins, which pose a significant threat to food and water quality. Highly pure saxitoxins are required for environmental monitoring and studies of cell physiology. Certain analogues have also shown promise as long-lasting and non-addictive pain blockers. However, the procurement of these compounds from natural sources is convoluted and unsustainable. This project aims to use the latest synthetic biology techniques to characterise, modify and express saxitoxin biosynthesis pathways, thereby providing a sustainable source of toxin analogues of value to industry and research. This novel 'green technology' will benefit the environment, human health and the Australian economy.Read moreRead less