The mechanism of membrane disruption by antimicrobial peptides. Bacterial resistance to antibiotics is a growing crisis in modern medicine. Antibacterial peptides from Australian frogs represent a new class of potent and selective antibacterial agents. Understanding how these peptides kill bacteria but not vertebrate cells could lead to the design of new drugs for pharmaceutical and/or clinical purposes.
Multifunctional biodegradable nanoparticles for enhanced DNA vaccine delivery. DNA vaccine, which shows better immunological and economic merits than conventional vaccines, suffers clinical failure due to the difficulty of delivering intact DNA molecules to relevant cells. This project seeks to develop smart polymer nanospheres to protect the DNA molecules from premature degradation in order to improve its efficacy.
A microbiological platform for the production of complex small molecules with important biological activities. Currently making complex chemicals such as medicines relies on harvesting rare natural resources or using complicated, energy intensive laboratory-based processes. This project will overcome these limitations by using a natural biological system to produce these chemicals, returning significant health and economic benefits to the nation.
Total Synthesis of Myxobacteria Metabolites and Analogues. This project will investigate the total chemical synthesis of complex myxobacteria metabolites. In addition, the synthesis of new analogues of some of these natural products will also be investigated. The project endeavours to develop new methods for chemical synthesis and also to produce new therapeutic products which may possess greater efficacy and superior biological activities than the natural compounds. Most significantly, this pro ....Total Synthesis of Myxobacteria Metabolites and Analogues. This project will investigate the total chemical synthesis of complex myxobacteria metabolites. In addition, the synthesis of new analogues of some of these natural products will also be investigated. The project endeavours to develop new methods for chemical synthesis and also to produce new therapeutic products which may possess greater efficacy and superior biological activities than the natural compounds. Most significantly, this project will deliver natural and new compounds for analysis of anti-cancer activity. The rewards of the development of new synthetic methods are enormous for the community and in the education of our scientists.Read moreRead less
Nicotinic receptor structure and function probed with conotoxins. Nicotinic receptors are intrinsic membrane proteins that play a role in communication in excitable cells, particularly in the nervous system. The primary goals of this project are to define the structural and functional determinants of nicotinic-conotoxin interactions at a molecular level, and develop new selective probes that advance neurophysiological research. The diversity and distribution of nicotinic receptor subtypes being ....Nicotinic receptor structure and function probed with conotoxins. Nicotinic receptors are intrinsic membrane proteins that play a role in communication in excitable cells, particularly in the nervous system. The primary goals of this project are to define the structural and functional determinants of nicotinic-conotoxin interactions at a molecular level, and develop new selective probes that advance neurophysiological research. The diversity and distribution of nicotinic receptor subtypes being uncovered through molecular biology and selective conotoxin probes presents an exciting opportunity for the discovery of new therapeutic agents.Read moreRead less
Atomic details of antimicrobial peptides at work in live cells. This project aims to develop methods to determine the detailed structure of biologically important molecules in live cells to better understand how biomolecular structure is related to disease. The structure at the atomic level of the molecules of life is usually characterised by crystal or solution studies in model systems. However, the structure of many biologically important molecules depends on their environment. Using new instr ....Atomic details of antimicrobial peptides at work in live cells. This project aims to develop methods to determine the detailed structure of biologically important molecules in live cells to better understand how biomolecular structure is related to disease. The structure at the atomic level of the molecules of life is usually characterised by crystal or solution studies in model systems. However, the structure of many biologically important molecules depends on their environment. Using new instrumentation and labelling schemes, the project plans to use nuclear magnetic resonance methods to study antibiotics and antimicrobial peptides in live bacteria and human cells. The goal is to resolve how these molecules cross cell membranes and how biomolecular structure is related to activity, which may advance development in biotechnology and therapeutic treatments against drug-resistant infections.Read moreRead less
Using chemistry to illuminate sulfoglycolysis, a major organosulfur pathway. This project aims to develop a detailed molecular description of the sulfoglycolysis pathway, a major pathway involved in cycling an abundant sulfolipid. The project will use an integrated chemical, biochemical and structural approach to illuminate how sulfoglycolysis degrades sulfolipid to access its elemental and energy constituents. Expected outcomes include an advanced understanding of the biosulfur cycle, the devel ....Using chemistry to illuminate sulfoglycolysis, a major organosulfur pathway. This project aims to develop a detailed molecular description of the sulfoglycolysis pathway, a major pathway involved in cycling an abundant sulfolipid. The project will use an integrated chemical, biochemical and structural approach to illuminate how sulfoglycolysis degrades sulfolipid to access its elemental and energy constituents. Expected outcomes include an advanced understanding of the biosulfur cycle, the development of new chemical approaches to manipulate sulfur cycling for agricultural and biotechnology applications, and deepened ties to leading international researchers. Potential benefits include new strategies to reduce dependence on agricultural fertilisers, promote gut wellbeing, and control insect pests.Read moreRead less
Chemical probes for the study of a unique enzyme from Mycobacterium tuberculosis. The design and chemical synthesis of molecules that selectively inhibit pathogen-specific enzymes is a validated approach toward new therapeutic agents. Mycobacterium tuberculosis contains a unique cytochrome P450 enzyme that catalyses an unusual chemical transformation to generate the product mycocyclosin. This research project will synthesise chemical probes to study the mechanism of this enzyme and the biologica ....Chemical probes for the study of a unique enzyme from Mycobacterium tuberculosis. The design and chemical synthesis of molecules that selectively inhibit pathogen-specific enzymes is a validated approach toward new therapeutic agents. Mycobacterium tuberculosis contains a unique cytochrome P450 enzyme that catalyses an unusual chemical transformation to generate the product mycocyclosin. This research project will synthesise chemical probes to study the mechanism of this enzyme and the biological role of mycocyclosin. Selective inhibitors of the enzyme will be developed, which will provide a foundation for the exploitation of these molecules in cellular research and medicine.Read moreRead less
Biogenesis inspired total synthesis of natural products. The project will study the chemical synthesis of a number of novel natural products. Most significantly, this project will deliver new methods for organic synthesis of complex molecules. The rewards from the total synthesis of bioactive compounds are enormous for the community and in the education and training of scientists.
Developing new tools for chemical biology. We will develop new synthetic strategies to support the development of small molecule chemical probes that bind with high affinity and specificity to a target protein. Such chemical probes are invaluable in elucidating the role of specific proteins in biological pathways. Our novel strategy aims to be rapid, efficient in its use of materials and widely applicable to a range of different protein targets. The core of our approach involves using biophysica ....Developing new tools for chemical biology. We will develop new synthetic strategies to support the development of small molecule chemical probes that bind with high affinity and specificity to a target protein. Such chemical probes are invaluable in elucidating the role of specific proteins in biological pathways. Our novel strategy aims to be rapid, efficient in its use of materials and widely applicable to a range of different protein targets. The core of our approach involves using biophysical binding assays to characterise compounds that are produced on small scale using parallel chemistry. This approach will enable better chemical probes to be developed more rapidly at lower cost than is currently possible.Read moreRead less