Fluorine-labelled proteins for NMR spectroscopy. The technique developed in this project has direct impact on pharmaceutical research: NMR spectroscopy is used routinely to identify chemical compounds that bind to protein targets. This project includes the development of novel assignment techniques of 19F-labelled proteins, so that 19F-NMR can be used to detect specific binding interactions. One of the methods proposed here is designed to reveal structural information about the binding mode in s ....Fluorine-labelled proteins for NMR spectroscopy. The technique developed in this project has direct impact on pharmaceutical research: NMR spectroscopy is used routinely to identify chemical compounds that bind to protein targets. This project includes the development of novel assignment techniques of 19F-labelled proteins, so that 19F-NMR can be used to detect specific binding interactions. One of the methods proposed here is designed to reveal structural information about the binding mode in solution with atomic detail. This knowledge can significantly accelerate drug development. It is otherwise only available from crystal structures that can not always be determined.Read moreRead less
Cross-Entropy Methods in Complex Biological Systems. The Cross-Entropy method provides a powerful new way to find superior solutions to complicated optimisation problems in biology, ranging from better design and implementation of medical treatments to an increased understanding of complex ecosystems.
Function and evolution of optical structures in nature. Designing optical structures that simultaneously satisfy multiple and conflicting criteria and satisfy difficult manufacturing constraints is technologically challenging. However, Nature has been doing this for millions of years. This project is a systematic study of optical structures in one of Nature's most diverse range of species: butterflies. The microstructures inside butterfly scales have an amazing diversity of geometries that produ ....Function and evolution of optical structures in nature. Designing optical structures that simultaneously satisfy multiple and conflicting criteria and satisfy difficult manufacturing constraints is technologically challenging. However, Nature has been doing this for millions of years. This project is a systematic study of optical structures in one of Nature's most diverse range of species: butterflies. The microstructures inside butterfly scales have an amazing diversity of geometries that produce structural colour and are amongst the most complex naturally occurring optical structures produced by a single cell.Read moreRead less
Computational Reconstruction of Cardiac Pacemaker Activation and Atrial Propagation. This study seeks to develop accurate computer models of electrical activity in pacemaker and atrial cells of the heart, in order to understand how the heartbeat originates and propagates across the atria during normal and abnormal rhythms. In Australia, atrial fibrillation represents the most common form of chronic cardiac arrhythmia encountered in clinical practice, as well as being a major risk factor in strok ....Computational Reconstruction of Cardiac Pacemaker Activation and Atrial Propagation. This study seeks to develop accurate computer models of electrical activity in pacemaker and atrial cells of the heart, in order to understand how the heartbeat originates and propagates across the atria during normal and abnormal rhythms. In Australia, atrial fibrillation represents the most common form of chronic cardiac arrhythmia encountered in clinical practice, as well as being a major risk factor in stroke. Accurate computer modelling of normal and abnormal heart rhythms will provide greater insights into the development of antiarrythmic drugs as well as advancing knowledge of key electrical phenomena in the heart.Read moreRead less
Conserving our native carnivores: the application of molecular genetics to the conservation management of quolls. Quolls, the largest native mammalian predators on mainland Australia, occupy a pivotal ecological niche. All species are declining and are threatened by a variety of interacting environmental processes. This program brings together seven wildlife agencies in a nationwide partnership for understanding and protecting quolls. We will provide new genetic data to test current populatio ....Conserving our native carnivores: the application of molecular genetics to the conservation management of quolls. Quolls, the largest native mammalian predators on mainland Australia, occupy a pivotal ecological niche. All species are declining and are threatened by a variety of interacting environmental processes. This program brings together seven wildlife agencies in a nationwide partnership for understanding and protecting quolls. We will provide new genetic data to test current population and conservation theories using four species of quolls as model taxa to inform us about past histories of populations and to measure parameters of importance to on-ground managers. Results of these projects will help guide management practices for both short- and long-term conservation of these species.Read moreRead less
Inbreeding and Amphibian Decline: from an Individual to a Global Perspective. Amphibian decline is not a phenomenon unique to overseas continents and countries. In the long line of research papers addressing this issue in the best science journals (e.g., Nature and Science), Australian frog decline has even been singled out for specific coverage. This project targets the interplay between habitat fragmentation, loss of genetic variation (inbreeding), and its effects on UV and pathogen resistance ....Inbreeding and Amphibian Decline: from an Individual to a Global Perspective. Amphibian decline is not a phenomenon unique to overseas continents and countries. In the long line of research papers addressing this issue in the best science journals (e.g., Nature and Science), Australian frog decline has even been singled out for specific coverage. This project targets the interplay between habitat fragmentation, loss of genetic variation (inbreeding), and its effects on UV and pathogen resistance in a laboratory model system. It integrates three disciplines (immunobiology, evolutionary genetics, and conservation biology) to resolve fundamental aspects of the drastic, ongoing disappearance of the most significant ecological indicator taxa known today (amphibians). Read moreRead less
Diversity out of a hybrid zone: the interplay of reinforcement and sexual selection in the formation of new species. How are there so many different species? Understanding how new species arise is a fundamental question because it explains current biodiversity and reveals the processes that will continue to give rise to new species in the future. An integral part of any animal species is who they choose to mate with, but how mate choice evolves to create new species remains poorly understood. He ....Diversity out of a hybrid zone: the interplay of reinforcement and sexual selection in the formation of new species. How are there so many different species? Understanding how new species arise is a fundamental question because it explains current biodiversity and reveals the processes that will continue to give rise to new species in the future. An integral part of any animal species is who they choose to mate with, but how mate choice evolves to create new species remains poorly understood. Here I will be studying the processes that affect the evolution of mate choice in an Australian rainforest frog hybrid zone. This system is uniquely suitable for providing internationally important insights into the evolutionary processes that form new species.Read moreRead less
The roles of relatedness and reproductive success in complex social systems of dolphins. Theories of the role of genetic relatedness and reproductive success in mammalian social behaviour have mostly been restricted to primates and carnivores. Coexisting alternative strategies within one population of bottlenose dolphins (Shark Bay WA) offer unprecedented opportunities for such investigations. The male alliances? complexity is unparalleled outside humans, and may require new theory. Some femal ....The roles of relatedness and reproductive success in complex social systems of dolphins. Theories of the role of genetic relatedness and reproductive success in mammalian social behaviour have mostly been restricted to primates and carnivores. Coexisting alternative strategies within one population of bottlenose dolphins (Shark Bay WA) offer unprecedented opportunities for such investigations. The male alliances? complexity is unparalleled outside humans, and may require new theory. Some female lineages show tool-use - rare outside humans, and virtually unknown in marine species. Our behavioural and genetic database has exceptional size, detail and duration for marine mammals, and is most valuable if continued while known individuals' offspring reach a stage where they can be sampled.Read moreRead less
Elucidating the mechanisms by which Scribble, Discs Large and Lethal Giant Larvae regulate epithelial polarity. Discs Large (Dlg) and Scribble are proteins that regulate cell shape by concentrating at particular regions within the cell and recruiting other proteins to that region. It is thought that the two proteins interact with each other, and with other proteins involved in protein trafficking and cell architecture, but it is not known how these events coordinate to produce a net outcome on ....Elucidating the mechanisms by which Scribble, Discs Large and Lethal Giant Larvae regulate epithelial polarity. Discs Large (Dlg) and Scribble are proteins that regulate cell shape by concentrating at particular regions within the cell and recruiting other proteins to that region. It is thought that the two proteins interact with each other, and with other proteins involved in protein trafficking and cell architecture, but it is not known how these events coordinate to produce a net outcome on cell shape. To answer these questions, the dynamic events involved in localization of Dlg, Scribble, and associated proteins will be determined, in mammalian cells and in whole organs of the vinegar fly.Read moreRead less
Zinc finger domains as scaffolds for protein engineering. While great advances have been made in pharmaceutical design and discovery, it is clear that new types of drugs are needed for the better management of a wide range of diseases (e.g. cancers, autoimmune diseases, viral infections). Many of these diseases arise from inappropriate interactions between intracellular biological macromolecules. My aim is to develop a range of novel therapeutic proteins based on naturally existing zinc-binding ....Zinc finger domains as scaffolds for protein engineering. While great advances have been made in pharmaceutical design and discovery, it is clear that new types of drugs are needed for the better management of a wide range of diseases (e.g. cancers, autoimmune diseases, viral infections). Many of these diseases arise from inappropriate interactions between intracellular biological macromolecules. My aim is to develop a range of novel therapeutic proteins based on naturally existing zinc-binding protein domains with the goal of selectively blocking these inappropriate interactions. Additionally, these engineered proteins have potential uses as biochemical tools such as to help delineate the functions of natural proteins with no known functions.Read moreRead less