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
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
Pathophysiological mechanisms in equine dyschondroplasia (osteochondrosis). Dyschondroplasia (osteochondrosis) is a developmental orthopaedic disease of horses, which causes significant wastage within the Thoroughbred racing industry. The disease affects growth cartilage beneath joint surfaces in such a way that cartilage fails to be replaced by bone, resulting in defects in the joint surface and lameness. This project will identify differences in gene expression between normal cartilage and ea ....Pathophysiological mechanisms in equine dyschondroplasia (osteochondrosis). Dyschondroplasia (osteochondrosis) is a developmental orthopaedic disease of horses, which causes significant wastage within the Thoroughbred racing industry. The disease affects growth cartilage beneath joint surfaces in such a way that cartilage fails to be replaced by bone, resulting in defects in the joint surface and lameness. This project will identify differences in gene expression between normal cartilage and early dyschondroplastic lesions, in order to identify the sequence of molecular events leading to induction of disease. The basic understanding of joint development obtained from this work will assist in the development of strategies to prevent and diagnose dyschondroplasia in horses.Read moreRead less
Metabolic Profiling of Human Embryonic Stem Cells. Stem cell therapies are becoming a commercial reality. Stem cell products have an estimated value of US$ 87 million this year and are predicted to be worth US$ 8.5 billion within a decade. Development of stem cell products will be an international research effort with many contributing to the final products. Research described here will augment this effort, strengthening Australia's contribution by developing novel intellectual property and appl ....Metabolic Profiling of Human Embryonic Stem Cells. Stem cell therapies are becoming a commercial reality. Stem cell products have an estimated value of US$ 87 million this year and are predicted to be worth US$ 8.5 billion within a decade. Development of stem cell products will be an international research effort with many contributing to the final products. Research described here will augment this effort, strengthening Australia's contribution by developing novel intellectual property and applications. The training of individuals skilled in stem cell research will add to Australia's pool of stem cell researchers. Individuals trained in this area will be paramount to maintaining Australia's research effort and in the application of these technologies into the Australian health sector.Read moreRead less
Mechanisms controlling enteroendocrine hormone secretion in human duodenum. This project aims to gain a deeper understanding of nutrient sensing pathways present in enteroendocrine cells within the human intestine. These cells control digestive function, blood glucose levels and food intake and are thus critical to digestion. This project will endeavour to be the first to assess the biology of human enteroendocrine cells and will use innovative approaches to deeply assess function from the level ....Mechanisms controlling enteroendocrine hormone secretion in human duodenum. This project aims to gain a deeper understanding of nutrient sensing pathways present in enteroendocrine cells within the human intestine. These cells control digestive function, blood glucose levels and food intake and are thus critical to digestion. This project will endeavour to be the first to assess the biology of human enteroendocrine cells and will use innovative approaches to deeply assess function from the level of the individual to isolated enteroendocrine cells.Read moreRead less
A proteomic approach to the identification of novel targets for allergy treatment. Eosinophils are involved in parasite immunity and in the pathology of allergic diseases including asthma. Eosinophil recruitment and activation is critical to their functional activity, but the relevant molecular mechanisms have not been fully elucidated. In the present proposal, a unique resource of eosinophils, at different stages of recruitment and activation, will be used for detailed proteomic analysis to ide ....A proteomic approach to the identification of novel targets for allergy treatment. Eosinophils are involved in parasite immunity and in the pathology of allergic diseases including asthma. Eosinophil recruitment and activation is critical to their functional activity, but the relevant molecular mechanisms have not been fully elucidated. In the present proposal, a unique resource of eosinophils, at different stages of recruitment and activation, will be used for detailed proteomic analysis to identify molecules and molecular pathways involved in eosinophil migration and activation. These studies may lead to novel anti-inflammatory strategies and more targeted drug treatments that will generate significant intellectual property and be of enormous benefit to allergy patients worldwide.Read moreRead less
Understanding platinum dissolution in biomedical stimulating electrodes. Platinum is the main material used in electrodes for neurostimulators like the cochlear implant. Platinum electrodes can experience dissolution during implantation, which can impact on their function. The mechanisms governing this dissolution process are complex and still not fully understood. This research aims to understand the chemical, electrical and biological factors that impact on platinum dissolution in electrodes. ....Understanding platinum dissolution in biomedical stimulating electrodes. Platinum is the main material used in electrodes for neurostimulators like the cochlear implant. Platinum electrodes can experience dissolution during implantation, which can impact on their function. The mechanisms governing this dissolution process are complex and still not fully understood. This research aims to understand the chemical, electrical and biological factors that impact on platinum dissolution in electrodes. It will also develop new 3D models to simulate conditions in the human body for more rapid testing of electrodes. The new knowledge generated will improve the accuracy of predictions of platinum dissolution, develop new approaches for minimising dissolution, and contribute to reducing need for animal experimentation.Read moreRead less
Identification of nuclear reprogramming factors in oocyte cytoplasm. The mature oocyte contains dominant factors that are capable of erasing tissue specific gene expression profiles of somatic cells. These reprogramming factors would be valuable for dedifferentiation of cells and for nuclear transfer in animal cloning. The research involves determination of reprogramming factors present in active cytoplasm following enucleation of the germinal vesicle, blockage of transcription and translation, ....Identification of nuclear reprogramming factors in oocyte cytoplasm. The mature oocyte contains dominant factors that are capable of erasing tissue specific gene expression profiles of somatic cells. These reprogramming factors would be valuable for dedifferentiation of cells and for nuclear transfer in animal cloning. The research involves determination of reprogramming factors present in active cytoplasm following enucleation of the germinal vesicle, blockage of transcription and translation, and timed cultures. The assays will involve maintenance of reprogramming ability and erasure of somatic gene transcription. By subtractive elimination the function of isolated proteins which are involved in reprogramming will be identified for potential recombinant production.Read moreRead less
Application of direct protein transduction of Stem Cell Factors to reprogram mouse and human somatic cells into pluripotent stem cells. This project aims to generate embryonic stem cell-like cells from human somatic cells, using direct protein transduction of defined factors, rather than through retroviral delivery. This will bring stem cell application closer to a therapeutic setting. The cells produced will be free from genetic modification and will yield products for patient-specific cell-ba ....Application of direct protein transduction of Stem Cell Factors to reprogram mouse and human somatic cells into pluripotent stem cells. This project aims to generate embryonic stem cell-like cells from human somatic cells, using direct protein transduction of defined factors, rather than through retroviral delivery. This will bring stem cell application closer to a therapeutic setting. The cells produced will be free from genetic modification and will yield products for patient-specific cell-based therapies that will be accepted by recipients without the need for immunosuppressant therapy. This development is expected to revolutionize the current approach to treating disease and injury, and is likely to result in the generation of highly marketable potent cell reprogramming therapeutics.Read moreRead less
Red Cell Polymorphisms and Malaria. Certain red blood cell disorders have been associated with innate protection against malaria infection. However many early studies were inconclusive. We intend to carry out a comprehensive study to investigate the effect of red blood cell differences on the invasion and/or growth of Plasmodium falciparum in vitro using improved techniques. Identification of red cell components involved in interaction with P.falciparum would give a better understanding of host ....Red Cell Polymorphisms and Malaria. Certain red blood cell disorders have been associated with innate protection against malaria infection. However many early studies were inconclusive. We intend to carry out a comprehensive study to investigate the effect of red blood cell differences on the invasion and/or growth of Plasmodium falciparum in vitro using improved techniques. Identification of red cell components involved in interaction with P.falciparum would give a better understanding of host parasite interactions which may in turn suggest novel approaches or pathways to persue. This may eventually lead to the development of novel therapeutics.
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