Rare isotopes as tracers of prosthesis debris. The incidence of knee replacement surgery in Australia is 30,000 per year. Limited by wear debris, the lifespan of knee implants is only 10-15 years and can be much shorter. Due to increasing life expectancy, many patients need several surgical procedures. As a multi-disciplinary team of materials-, isotope-tracing- and medical-experts, we aim to understand and monitor wear debris in prostheses. Knee replacement surgery alone imposes a high burden o ....Rare isotopes as tracers of prosthesis debris. The incidence of knee replacement surgery in Australia is 30,000 per year. Limited by wear debris, the lifespan of knee implants is only 10-15 years and can be much shorter. Due to increasing life expectancy, many patients need several surgical procedures. As a multi-disciplinary team of materials-, isotope-tracing- and medical-experts, we aim to understand and monitor wear debris in prostheses. Knee replacement surgery alone imposes a high burden of annually half a billion dollars on the Australian health budget. Controlling and reducing wear debris in prosthesis joints would reduce these costs and improve patients' quality of life.Read moreRead less
Neurons isolated from embryonic stem cells as functional models for drug discovery. By using gene expression-based selection criteria embryonic stem cells can be driven to differentiate into specific neuronal lineages which show many of the morphological characteristics and immunocytochemical features of neurons in culture. There is, however, comparatively little evidence indicating that these stem cell-derived neurons actually behave as neurons. Our aim is to characterise and contrast four ne ....Neurons isolated from embryonic stem cells as functional models for drug discovery. By using gene expression-based selection criteria embryonic stem cells can be driven to differentiate into specific neuronal lineages which show many of the morphological characteristics and immunocytochemical features of neurons in culture. There is, however, comparatively little evidence indicating that these stem cell-derived neurons actually behave as neurons. Our aim is to characterise and contrast four neuronal cell cultures established with gene-based selection criteria. These cultures will be characterised by gene expression, immunocytochemistry, radiolabelled neurotransmitter release, electrophysiology and Ca2+ imaging studies. This study will highlight the functional effects of gene selection procedures upon stem cell-derived neurons.Read moreRead less
Why is the photosynthetic CO2-fixing enzyme, Rubisco, so inefficient? Dissection of the catalytic chemistry by computational simulation and experimental testing. Fixation of CO2 by the enzyme Rubisco during photosynthesis produces organic compounds which feed all life. Despite this critical role, Rubisco catalyses its reaction sluggishly and, worse, discriminates poorly between CO2 and O2, leading to useless products. Our combined expertise equips us to analyse Rubisco's mechanism using quantum- ....Why is the photosynthetic CO2-fixing enzyme, Rubisco, so inefficient? Dissection of the catalytic chemistry by computational simulation and experimental testing. Fixation of CO2 by the enzyme Rubisco during photosynthesis produces organic compounds which feed all life. Despite this critical role, Rubisco catalyses its reaction sluggishly and, worse, discriminates poorly between CO2 and O2, leading to useless products. Our combined expertise equips us to analyse Rubisco's mechanism using quantum-chemical methods and then test predictions experimentally. We will capitalise on our previous successful studies of Rubisco by addressing emergent issues which are the keys to understanding catalytic efficiency and CO2/O2 selectivity: the roles of a carbamylated lysine; the way CO2 addition is rendered irreversible; and the spin inversion inherent in O2 addition.Read moreRead less
New Techniques for Structural Biology and Directed Molecular Evolution. This PhD program will equip an Australian graduate with advanced training in techniques in molecular genetics and protein chemistry that are currently in high demand by the biotechnology industry, and also provide him/her with direct experience of an industrial R&D laboratory environment. Moreover, it will establish a basis for further collaboration between a leading University-based research laboratory and an established R& ....New Techniques for Structural Biology and Directed Molecular Evolution. This PhD program will equip an Australian graduate with advanced training in techniques in molecular genetics and protein chemistry that are currently in high demand by the biotechnology industry, and also provide him/her with direct experience of an industrial R&D laboratory environment. Moreover, it will establish a basis for further collaboration between a leading University-based research laboratory and an established R&D company that will lead to development of new techniques for use in biotechnology in Australia and overseas.Read moreRead less
Regulation of large artery stiffness by endothelium-derived mediators and effects on the arterial pressure waveform. Stiffening of arteries is an important cardiovascular risk factor and increases with age, high blood pressure, high cholesterol and diabetes. Cells that line the blood vessels (endothelial cells), become damaged and this reduces the available amount of a dilator substance, nitric oxide, and increases the activity of a constrictor substance, endothelin-1. We have shown that nitric ....Regulation of large artery stiffness by endothelium-derived mediators and effects on the arterial pressure waveform. Stiffening of arteries is an important cardiovascular risk factor and increases with age, high blood pressure, high cholesterol and diabetes. Cells that line the blood vessels (endothelial cells), become damaged and this reduces the available amount of a dilator substance, nitric oxide, and increases the activity of a constrictor substance, endothelin-1. We have shown that nitric oxide regulates large artery stiffness and we believe that other endothelial mediators are also important regulators. Therefore, we aim to explore this in a series of studies. Regulation of stiffness of large arteries will improve treatment of age-related cardiovascular disease (eg isolated systolic hypertension)Read moreRead less
Elucidation of genetic and physiological factors controlling biosynthesis of sesquiterpenoids in sandalwood, Santalum spp. Plantation sandalwood removes pressure from natural populations and is a profitable long term investment. Australia is in a highly competitive position with regards to market supply but this cannot be taken for granted. This research seeks to understand the complex biology of sandalwood using the latest genomic and molecular technologies. This knowledge will be applied thro ....Elucidation of genetic and physiological factors controlling biosynthesis of sesquiterpenoids in sandalwood, Santalum spp. Plantation sandalwood removes pressure from natural populations and is a profitable long term investment. Australia is in a highly competitive position with regards to market supply but this cannot be taken for granted. This research seeks to understand the complex biology of sandalwood using the latest genomic and molecular technologies. This knowledge will be applied through directed, marker-assisted tree selection and improved plantation management. Ultimately we are developing a highly advanced production system with which Australia can lead Sandalwood production. Sandalwood plantations use a variety of native perennial hosts, increase biodiversity, help manage underground water resources and address carbon sequestration demands.Read moreRead less
Multipurpose separation platforms for protein purification. Over the next decades, many new therapies and products will be needed to enhance the quality of human life. Biopharmaceuticals and other protein-based products will thus be increasingly in demand. This will require significant improvements in biotechnological procedures, particularly sophisticated purification technologies. Through the development of a novel technology, this project is anticipated to significantly contribute to these so ....Multipurpose separation platforms for protein purification. Over the next decades, many new therapies and products will be needed to enhance the quality of human life. Biopharmaceuticals and other protein-based products will thus be increasingly in demand. This will require significant improvements in biotechnological procedures, particularly sophisticated purification technologies. Through the development of a novel technology, this project is anticipated to significantly contribute to these societal needs and provide a new way to purify these important molecules. National and community benefits will accrue from this scientific innovation and from its application, which is expected to provide more efficient manufacturing opportunities for key biotechnology industries.Read moreRead less
Novel Technologies for the Purification of Recombinant Proteins. Availability of enabling technologies for the large-scale purification of recombinant proteins is an essential requirement of the biotechnology industry. This project aims to integrate two concepts in molecular biorecognition. New modalities of immobilised metal ion affinity chromatography will be linked with the selection of new types of peptide affinity handles that can be inserted by genetic engineering methods into proteins pro ....Novel Technologies for the Purification of Recombinant Proteins. Availability of enabling technologies for the large-scale purification of recombinant proteins is an essential requirement of the biotechnology industry. This project aims to integrate two concepts in molecular biorecognition. New modalities of immobilised metal ion affinity chromatography will be linked with the selection of new types of peptide affinity handles that can be inserted by genetic engineering methods into proteins produced by biotechnological procedures. The approach followed then allows these handles to be removed following isolation of the target protein. This project could thus lead to a considerable advance in the manufacture of recombinant proteins intended for human therapy.Read moreRead less
Functional characterisation of neurons derived from embryonic stem cells and NS cells. The ability to obtain specific neurons from NS cells will revolutionise the study of nerve function, will allow the establishment of much-improved models for discovery of new drugs, and will define how enriched populations of neural cells can be obtained for applications in treatment of neurodegenerative diseases. The project will provide vital data for the emerging biotechnology industry associated will appl ....Functional characterisation of neurons derived from embryonic stem cells and NS cells. The ability to obtain specific neurons from NS cells will revolutionise the study of nerve function, will allow the establishment of much-improved models for discovery of new drugs, and will define how enriched populations of neural cells can be obtained for applications in treatment of neurodegenerative diseases. The project will provide vital data for the emerging biotechnology industry associated will applications of stem cell biology, and will stimulate clinical researchers to investigate the therapeutic potential of cell derived from NS cells.Read moreRead less
Indian Sandalwood: genetic and oil diversity, and oil biochemistry of the Australian germplasm collection. The main aim is to improve the commerciality of the sandalwood industry in tropical Australia through smarter tree selection and breeding by development of knowledge of oil quality and quantity, oil biochemistry and DNA marker-assisted selection of the germplasm collection available in Australia.