Structure and dynamics of a multiprotein-mRNA complex involved in the regulation of gene expression. RNA/protein interactions are now recognised as a major control point in the regulation of gene-expression. Proteins such as HuR and the poly(C)-binding proteins (PCBPs) act to stabilise and transport specific messenger (m)RNAs, and thus determine their translation levels. In contrast to such an important function, very little is known about these protein/mRNA interactions at an atomic level. The ....Structure and dynamics of a multiprotein-mRNA complex involved in the regulation of gene expression. RNA/protein interactions are now recognised as a major control point in the regulation of gene-expression. Proteins such as HuR and the poly(C)-binding proteins (PCBPs) act to stabilise and transport specific messenger (m)RNAs, and thus determine their translation levels. In contrast to such an important function, very little is known about these protein/mRNA interactions at an atomic level. The current study will investigate the structural and biophysical properties of a recently discovered HuR/PCBP/mRNA complex implicated in the regulation of androgen receptor expression. This information has the potential to assist in the development of drugs to reduce AR expression in prostate cancer.Read moreRead less
Guarding and evolving the genome: interactions between DNA-repair enzymes and damaged DNA. The application of structural biology techniques to the area of DNA repair allows us to understand the full implications linking genes and proteins to the molecular mechanisms of diseases such as cancer and hereditory conditions. Studies in this highly internationally competitive area are already established in the Bond laboratory, which has recently relocated to Australia. The use of forward-thinking stru ....Guarding and evolving the genome: interactions between DNA-repair enzymes and damaged DNA. The application of structural biology techniques to the area of DNA repair allows us to understand the full implications linking genes and proteins to the molecular mechanisms of diseases such as cancer and hereditory conditions. Studies in this highly internationally competitive area are already established in the Bond laboratory, which has recently relocated to Australia. The use of forward-thinking structural biology approaches to solve difficult technical problems will foster collaborations within Australia and with leading laboratories abroad, providing excellent up-to-date research training for students and postdoctoral researchers.
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Imaging of properties of coherent elastic light scattering from turbid biological media. Imaging with coherent, elastically-scattered light for visualisation of thick-tissue morphology in vivo, or of cells buried deep in a turbid medium, remains a major challenge. We adopt an alternative approach of imaging of properties of light scattering based on regarding cellular tissue as a spatially-varying refractive-index continuum which encodes scattered light. We propose new methodologies to infer t ....Imaging of properties of coherent elastic light scattering from turbid biological media. Imaging with coherent, elastically-scattered light for visualisation of thick-tissue morphology in vivo, or of cells buried deep in a turbid medium, remains a major challenge. We adopt an alternative approach of imaging of properties of light scattering based on regarding cellular tissue as a spatially-varying refractive-index continuum which encodes scattered light. We propose new methodologies to infer tissue state and morphology indirectly based on phase delay, speckle, and angle-resolved scattering. We will break new ground in correlating the structure and function of in situ epithelial tissue and cells to light scattering enabling, e.g., the detection of mitosis and apoptosis in cells buried in thick, turbid media, and of cancers and precancers in vivo.Read moreRead less
To implement and evaluate flexible models of palliative care service delivery for terminally ill people living alone at home. Provision of evaluated services for this growing population group will lead to better planning and implementation of care being delivered at home, improved quality of life, increased capacity to die at home, and a reduction in hospitalisations and other health care costs.
Techniques for probing biological media with holographic angular scattering spectroscopy. Huge effort in the biological and medical sciences is spent in using simple software to laboriously mark, count and measure cells and structures in microscope images of samples. We could replace this incredibly inefficient process in many instances with single-shot size-map images of unstained samples. If depth selectivity can be added, we could perform non-invasive measurements on animals, making a huge re ....Techniques for probing biological media with holographic angular scattering spectroscopy. Huge effort in the biological and medical sciences is spent in using simple software to laboriously mark, count and measure cells and structures in microscope images of samples. We could replace this incredibly inefficient process in many instances with single-shot size-map images of unstained samples. If depth selectivity can be added, we could perform non-invasive measurements on animals, making a huge reduction in their usage. We could assess thick tissues enabling early noninvasive diagnosis of malignancy in tumours in situ or muscle characterization for meat quality or muscular dystrophy. These benefits impact on research, animal ethics, and on health, and have commercial potential in life and medical sciences, and the meat industry.Read moreRead less
Advances in optical coherence tomography. We propose to continue our research into the biomedical imaging technique of optical coherence tomography by making substantial new advances in the key areas of ultra-broad bandwidth operation, coincident confocal gate scanning, and dispersion compensation. These advances are aimed at improving resolution to the 1-5 micron range, which should allow a breakthrough to sub-cellular in vivo imaging, making visible sample histology in situ, which is currentl ....Advances in optical coherence tomography. We propose to continue our research into the biomedical imaging technique of optical coherence tomography by making substantial new advances in the key areas of ultra-broad bandwidth operation, coincident confocal gate scanning, and dispersion compensation. These advances are aimed at improving resolution to the 1-5 micron range, which should allow a breakthrough to sub-cellular in vivo imaging, making visible sample histology in situ, which is currently not possible. We also plan to make advances in the key area of scanning delay line technology by employing acousto-optics in OCT for the first time. Acousto-optics conveys advantages in no-moving-parts, scan-speed and accuracy.Read moreRead less
Optical coherence elastography - High-resolution medical imaging of tissue mechanical properties. This project brings together an international, multi-disciplinary team to develop innovative, high-resolution techniques to identify diseased tissue. Success will result in a new medical imaging technique allowing clinicians to quantify the mechanical properties of tissue, effectively creating a high-resolution image of what the tissue 'feels' like. This may help them to more accurately identify can ....Optical coherence elastography - High-resolution medical imaging of tissue mechanical properties. This project brings together an international, multi-disciplinary team to develop innovative, high-resolution techniques to identify diseased tissue. Success will result in a new medical imaging technique allowing clinicians to quantify the mechanical properties of tissue, effectively creating a high-resolution image of what the tissue 'feels' like. This may help them to more accurately identify cancerous tissue during surgery and reduce rates of recurrence. It could aid in tissue engineering and regeneration and will provide a new database of tissue mechanical properties. The project will position Australia as a leader in this newly developing medical imaging technology, with significant potential for commercialisation.Read moreRead less
Development of a prime-boost anti-cancer vaccine. New vaccination strategies are urgently needed for a variety of diseases, including cancer. The problem with cancer vaccines is that it is difficult to trigger a response to a self protein. We propose that a prime-boost vaccination, using yellow fever virus and modified vaccinia virus ankara, could create very strong responses against tumor antigens. This approach can be patented and can revive that field of tumor vaccination, which is currently ....Development of a prime-boost anti-cancer vaccine. New vaccination strategies are urgently needed for a variety of diseases, including cancer. The problem with cancer vaccines is that it is difficult to trigger a response to a self protein. We propose that a prime-boost vaccination, using yellow fever virus and modified vaccinia virus ankara, could create very strong responses against tumor antigens. This approach can be patented and can revive that field of tumor vaccination, which is currently restrained by the difficulty of breaking immunological tolerance. We envisage the construction of a anti-cancer vaccine vector with obvious market potential. An exciting prospect is that this approach could be used as a prophylactic vaccine and possibly also as a therapeutic vaccine.Read moreRead less
Terahertz and optical coherence tomography for improved cancer imaging. This project aims to improve cancer imaging by combining two complimentary, novel techniques. Its success will create an internationally leading position for Australia in cutting-edge research in optical and terahertz biomedical imaging. This innovative, fundamental research will expand Australia's research capacity in imaging sciences. The nation will benefit from new medical diagnostic techniques that will improve the dete ....Terahertz and optical coherence tomography for improved cancer imaging. This project aims to improve cancer imaging by combining two complimentary, novel techniques. Its success will create an internationally leading position for Australia in cutting-edge research in optical and terahertz biomedical imaging. This innovative, fundamental research will expand Australia's research capacity in imaging sciences. The nation will benefit from new medical diagnostic techniques that will improve the detection and treatment of cancer; as well as aid the clinical assessment of burns. This multidisciplinary, internationally collaborative research has additional wide ranging benefits in biology, medicine, pharmaceutical science and national security.Read moreRead less
Magnetic Nanoparticles for Biomedical Applications. This project will develop biocompatible magnetic nanoparticles for future generations of therapeutic and diagnostic applications. Applications include the reduction in overall toxicity of chemo- and radio- therapy by magnetic target drug delivery, enhanced ability to detect and diagnose diseases using magnetic binding/sorting techniques and an enhanced ability to repair detached retinas. The development of these products provides the potential ....Magnetic Nanoparticles for Biomedical Applications. This project will develop biocompatible magnetic nanoparticles for future generations of therapeutic and diagnostic applications. Applications include the reduction in overall toxicity of chemo- and radio- therapy by magnetic target drug delivery, enhanced ability to detect and diagnose diseases using magnetic binding/sorting techniques and an enhanced ability to repair detached retinas. The development of these products provides the potential for the development of new commercial opportunities in biotechnology and biomedical science in which Australia has an excellent track record. The project will also enhance Australia's capabilities in both nanotechnologiocal and biotechnological sciences.Read moreRead less