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Novel kinases: How do they regulate epithelial ion transport, and what is their role in epithelial function? The project will produce the knowledge of fundamental physiology that will lead to novel approaches for treating respiratory and gastrointestinal infections and cystic fibrosis, as well as for the accumulation of fluid in the lungs and abdomen that accompany many advanced malignancies. It thus has the potential to have a significant economic and social impact in Australia and internation ....Novel kinases: How do they regulate epithelial ion transport, and what is their role in epithelial function? The project will produce the knowledge of fundamental physiology that will lead to novel approaches for treating respiratory and gastrointestinal infections and cystic fibrosis, as well as for the accumulation of fluid in the lungs and abdomen that accompany many advanced malignancies. It thus has the potential to have a significant economic and social impact in Australia and internationally. Furthermore, it will provide advanced training in research methods to Australian scientists, equipping them to undertake challenging and interesting positions in the medical and life sciences and beyond.Read moreRead less
Environmental control of genetic/phenotypic interactions in lung development: An evolutionary perspective. Vertebrate lungs all contain morphologically and functionally similar lung lining cells. However, the cellular arrangement (i.e. lung morphology) and the function of the surfactant these cells produce, differs dramatically between species. Hence, a subset of highly conserved lung-specific genes coincides with spectacular phenotypic diversity. How has this diversity evolved? Do environmental ....Environmental control of genetic/phenotypic interactions in lung development: An evolutionary perspective. Vertebrate lungs all contain morphologically and functionally similar lung lining cells. However, the cellular arrangement (i.e. lung morphology) and the function of the surfactant these cells produce, differs dramatically between species. Hence, a subset of highly conserved lung-specific genes coincides with spectacular phenotypic diversity. How has this diversity evolved? Do environmental conditions, birth strategy or phylogenetic relationships determine lung phenotype? We will experimentally manipulate developing lungs and cells to demonstrate how environmental conditions (temperature, oxygen, lung-fluid regulation and neuro-hormonal input) promote evolutionary processes by altering gene expression, protein/lipid synthesis, cellular differentiation and hence lung morphology/function in animals with different birth strategies.Read moreRead less
A new paradigm for surfactant composition and function - how do lungs cope with stress? Our research will increase the understanding of the scope of change and precise molecular interactions occurring in the surfactant lipids and proteins of animals under physiological stress. The novel insights will improve the treatment of lung diseases (such as chronic obstructive pulmonary disease and acute lung injury). We have formed a team of international surfactant researchers all experts in state-of-th ....A new paradigm for surfactant composition and function - how do lungs cope with stress? Our research will increase the understanding of the scope of change and precise molecular interactions occurring in the surfactant lipids and proteins of animals under physiological stress. The novel insights will improve the treatment of lung diseases (such as chronic obstructive pulmonary disease and acute lung injury). We have formed a team of international surfactant researchers all experts in state-of-the-art chemical and biophysical technologies relating to surfactant. These collaborations will bring new technological applications to Australia and provide outstanding cross-disciplinary training for postgraduate students and research staff at the interface between animal physiology, biophysical chemistry and respiratory medicine.Read moreRead less
Structural determination of respiratory membrane protein complexes by X-ray crystallography. Membrane proteins form only 0.3% of the available protein structures in the protein data bank (PDB), yet 30% of the proteins in the human genome and 50% of human drug targets are membrane proteins. We have managed to increase the success rate through rational screening and development of new crystallization screens, with downstream implications for basic and medical research. Results from this proposal w ....Structural determination of respiratory membrane protein complexes by X-ray crystallography. Membrane proteins form only 0.3% of the available protein structures in the protein data bank (PDB), yet 30% of the proteins in the human genome and 50% of human drug targets are membrane proteins. We have managed to increase the success rate through rational screening and development of new crystallization screens, with downstream implications for basic and medical research. Results from this proposal will receive international recognition and will encourage more research in this field, attracting international funding, and create new research opportunities. 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