Navigating tipping points in complex dynamical systems. This project aims to use applied mathematics to investigate the onset of tipping points in dynamical systems. Working with clinicians and practicing engineers, the project aims to contribute to the development of new treatment regimes for dynamical diseases and develop improved management strategies for resource focussed engineering industries. This should provide significant benefit to many areas, including the personalised treatment of di ....Navigating tipping points in complex dynamical systems. This project aims to use applied mathematics to investigate the onset of tipping points in dynamical systems. Working with clinicians and practicing engineers, the project aims to contribute to the development of new treatment regimes for dynamical diseases and develop improved management strategies for resource focussed engineering industries. This should provide significant benefit to many areas, including the personalised treatment of disease.Read moreRead less
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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Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims ....Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims to determine how the Bak inhibitors function and to provide valuable insights into the normal mechanisms regulating Bak activity.Read moreRead less
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
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
Quantitative multi-modal optical imaging of deep tissue. This project aims to create new tools to quantify the structural and functional properties of tissue. Combining multiple optical imaging technologies (multi-modal) into a single, miniaturised probe, these tools could enable physiologists and biomedical researchers to obtain new insight into disease. Encasing the highly miniaturised probe within a medical needle is aimed to allow insertion of the 'needle probe' deep into tissue, extending o ....Quantitative multi-modal optical imaging of deep tissue. This project aims to create new tools to quantify the structural and functional properties of tissue. Combining multiple optical imaging technologies (multi-modal) into a single, miniaturised probe, these tools could enable physiologists and biomedical researchers to obtain new insight into disease. Encasing the highly miniaturised probe within a medical needle is aimed to allow insertion of the 'needle probe' deep into tissue, extending optical imaging to areas not previously accessible. The project could develop novel quantification models to allow longitudinal assessment and comparison between subjects. Validating the tools with specific biomarkers, it could provide outcomes in breast and liver cancer, and a framework to explore other diseases.Read moreRead less
High-resolution elastography – Using optical micro-imaging of tissue mechanics to identify disease. Optical elastography, the probing of tissue’s micro-mechanical properties using optical imaging, offers new tools in surgery and pathology to improve differentiation of tissues. This project lays the groundwork for optical elastography to become a new medical micro-imaging modality by removing impediments to progress in this rapidly emerging field. On the micro-scale, between the scales of cells a ....High-resolution elastography – Using optical micro-imaging of tissue mechanics to identify disease. Optical elastography, the probing of tissue’s micro-mechanical properties using optical imaging, offers new tools in surgery and pathology to improve differentiation of tissues. This project lays the groundwork for optical elastography to become a new medical micro-imaging modality by removing impediments to progress in this rapidly emerging field. On the micro-scale, between the scales of cells and organs. This project will elucidate the origins of tissue mechanical contrast and determine limits on its measurement. It will develop a suite of probes: noncontact, endoscopic and needle, to enable access to all tissues in the body. To progress toward a new modality and inform our research, the project will test our tools on breast cancer tissues and burn scars.Read moreRead less
Supercritical-microfluidics technology for targeted delivery to the colon. This research will develop nanosystems to target delivery of drugs to the colon. Our nanosystems will permit the combination of clinically used chemotherapy drugs within a single dosage form. This will improve the efficiency of delivery to the colon while reducing unwanted side-effects. A novel supercritical microfluidics system will be developed to produce therapeutic nano-carriers in a continuous mode with lower labour ....Supercritical-microfluidics technology for targeted delivery to the colon. This research will develop nanosystems to target delivery of drugs to the colon. Our nanosystems will permit the combination of clinically used chemotherapy drugs within a single dosage form. This will improve the efficiency of delivery to the colon while reducing unwanted side-effects. A novel supercritical microfluidics system will be developed to produce therapeutic nano-carriers in a continuous mode with lower labour requirement, higher production rate and better quality control than conventional production methods. The new process will combine benefits from both supercritical fluid technology (green process) and microfluidics (high mass & heat transfer).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