Discovery Early Career Researcher Award - Grant ID: DE120101331
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Fundamental electromagnetic modelling of light-biological tissue interactions: a platform for future medical microscopy. Methods for modelling the fundamental electromagnetic interaction of light with biological tissue will be developed. This will allow a range of biomedical optical images to be properly interpreted ultimately leading to the holy grail of quick and minimally invasive methods for detecting cancer.
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
Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specifi ....Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specific key genes deregulated in cancer, to correct their expression and stably reprogram the phenotype of the tumour cell in a normal-like state. It outlines the engineering of novel synthetic agents to block specific protein-protein interactions in cancer cells and to induce potent tumour cell death. This work will generate novel and selective therapeutics to treat un-curable forms of tumours.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
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