Epilepsy: Molecular Basis And Mechanisms In The Era Of Functional Genomics
Funder
National Health and Medical Research Council
Funding Amount
$12,062,533.00
Summary
The team comprises of neurologists with a special interest in epilepsy (both adult and child) molecular geneticists, physiologists and brain imaging specialists. The team leads the world in the discovery of the genetic causes of epilepsy and epilepsy associated with intellectual disability. The team will continue to identify the genes underlying epilepsy, and study how genetic variations result in the development of seizures and will continue to develop advanced imaging techniques for these stud ....The team comprises of neurologists with a special interest in epilepsy (both adult and child) molecular geneticists, physiologists and brain imaging specialists. The team leads the world in the discovery of the genetic causes of epilepsy and epilepsy associated with intellectual disability. The team will continue to identify the genes underlying epilepsy, and study how genetic variations result in the development of seizures and will continue to develop advanced imaging techniques for these studies. This will include extensive laboratory studies, including the development of mice with the exact mutations that we find in the human condition. Stateof-the-art imaging techniques with magnetic resonance and positron emission tomography are used in human subjects to further understand the effects of the mutations on the structure and function of the brain. This will allow deep understanding of how seizures develop and may lead to new diagnostic methods and treatments. The laboratory and clinical aspects of the research are tightly integrated in this internationally leading collaborative program.Read moreRead less
Targeting NDM-producing ‘superbugs’: Optimising Novel Combinations With ‘old’ Polymyxins Using Pharmacological, Molecular Imaging And Systems Biology Approaches
Funder
National Health and Medical Research Council
Funding Amount
$582,732.00
Summary
Rapid global spread of so-called NDM-producing bacterial ‘superbugs’ is presenting a major medical challenge. Without new antibiotics under development, polymyxin is becoming the only effective antibiotic. Unfortunately we recently revealed that treatment with polymyxin alone can rapidly lead to resistance in NDM-producing ‘superbugs’. This project will employ new tools to optimise rational polymyxin combinations, thereby providing urgently needed information to clinicians for treating these ver ....Rapid global spread of so-called NDM-producing bacterial ‘superbugs’ is presenting a major medical challenge. Without new antibiotics under development, polymyxin is becoming the only effective antibiotic. Unfortunately we recently revealed that treatment with polymyxin alone can rapidly lead to resistance in NDM-producing ‘superbugs’. This project will employ new tools to optimise rational polymyxin combinations, thereby providing urgently needed information to clinicians for treating these very problematic infections.Read moreRead less
Single Shot X-ray Tomography For Real-Time Functional X-ray Imaging
Funder
National Health and Medical Research Council
Funding Amount
$322,641.00
Summary
Computed Tomography (CT) scanners produce three-dimensional images of vital organs that cannot be obtained by conventional two-dimensional (single projection) x-ray radiographs. However, the radiation exposure is hundreds of times higher than conventional radiography. We will develop the world’s first CT scanner that uses no more radiation than a single conventional x-ray image that will provide four-dimensional reconstructions of a patient’s moving internal organs.
Atomic scale imaging with high coherence electrons and ions. This project aims to combine a cold atom electron-ion source with a commercial microscope column for atomic-scale imaging in biosciences and materials science. Nanoscale imaging with electron and ion microscopy are tools for investigating the world at the atomic scale, underpinning development in modern technologies from semiconductor devices to medical treatments. This project will use ideas from laser cooling of atoms and atom optics ....Atomic scale imaging with high coherence electrons and ions. This project aims to combine a cold atom electron-ion source with a commercial microscope column for atomic-scale imaging in biosciences and materials science. Nanoscale imaging with electron and ion microscopy are tools for investigating the world at the atomic scale, underpinning development in modern technologies from semiconductor devices to medical treatments. This project will use ideas from laser cooling of atoms and atom optics to achieve new imaging modalities for time-lapse imaging of fundamental processes at the nano-scale. It will allow increasingly small scale resolution of fundamental processes at the nano-scale.Read moreRead less
Novel advances in sub-nanometer imaging. After two decades of research the first wave of applications in nanotechnology and nanobiology is breaking. Immediately key to further progress in both areas is the ability to characterise the structure of such systems and also their evolution on very short time scales. This research project places Australia at the forefront in this endeavour.
Visualising chromatin changes in 3 dimensions: super to ultra resolution. Packaging of genomic information into the nucleus of a cell necessitates the formation of tightly compacted and highly organized genomic structures within the nucleus, a configuration that is inherently repressive for gene transcription. Hence, mechanisms that alter the spatial organisation of DNA are critical to enable a variety of genome functions, including DNA transcription. This proposal will utilise novel adaptations ....Visualising chromatin changes in 3 dimensions: super to ultra resolution. Packaging of genomic information into the nucleus of a cell necessitates the formation of tightly compacted and highly organized genomic structures within the nucleus, a configuration that is inherently repressive for gene transcription. Hence, mechanisms that alter the spatial organisation of DNA are critical to enable a variety of genome functions, including DNA transcription. This proposal will utilise novel adaptations of super resolution microscopy to visualise in 3 dimensions how changes in chromatin modifications impact genome spatial organisation within the nucleus, and how this then links to cellular differentiation. This will provide a picture of how spatial organisation within the nucleus supports general cell differentiation.
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Discovery Early Career Researcher Award - Grant ID: DE240100992
Funder
Australian Research Council
Funding Amount
$448,237.00
Summary
New methods to capture protein dynamics of the TSC-mTOR signalling axis. Protein flexibility, the way proteins move, has a major role in how they function. However, we still do not have the tools to analyse this flexibility. Our cells have evolved many complex and flexible systems to sense and respond to their environment. For example, the TSC-mTOR system is found across life, from baker’s yeast to humans, however it remains poorly understood. This proposal will study TSC as an exemplar to devel ....New methods to capture protein dynamics of the TSC-mTOR signalling axis. Protein flexibility, the way proteins move, has a major role in how they function. However, we still do not have the tools to analyse this flexibility. Our cells have evolved many complex and flexible systems to sense and respond to their environment. For example, the TSC-mTOR system is found across life, from baker’s yeast to humans, however it remains poorly understood. This proposal will study TSC as an exemplar to develop novel machine-learning approaches to capture protein flexibility and shape. This proposal will advance fundamental understanding of the TSC-mTOR pathway and build transformative methodologies to study flexible proteins more broadly.Read moreRead less
Developing Interpretable Machine Learning Models For Clinical Imaging And Single-cell Genomics
Funder
National Health and Medical Research Council
Funding Amount
$1,312,250.00
Summary
Machine learning methods will be vital to make best use of the deluge of data generated by high-throughput technologies in biomedical science. To get the most out of these models, however, we need to be able to unpack the 'black box'. I will use curated clinical and public research data to benchmark and develop interpretable deep learning models and software tools. These models will be used for breast cancer screening programs and for analysis of complex, large-scale single-cell genomics data.
In depth characterisation of the gamma delta T cell immune synapse. This project aims to comprehensively characterise the activation principles of gamma delta T cells. These cells have an understudied but central role in vertebrate immunity and development. A missing piece of the puzzle is how gamma delta T cells sense stress and how this signal leads to activation. Expected outcomes include the generation of fundamental knowledge in immunology and structural biology. This proposal uses high-ski ....In depth characterisation of the gamma delta T cell immune synapse. This project aims to comprehensively characterise the activation principles of gamma delta T cells. These cells have an understudied but central role in vertebrate immunity and development. A missing piece of the puzzle is how gamma delta T cells sense stress and how this signal leads to activation. Expected outcomes include the generation of fundamental knowledge in immunology and structural biology. This proposal uses high-skilled techniques, including cryo-electron microscopy and single-molecule imaging and holds ancillary benefits to postgraduate students. Anticipated outcomes include influential publications, building a critical mass of expertise in Australia and fostering international collaborations with Australia at the epicentre.Read moreRead less
From The Synchrotron To The Clinic: Translation Of A Novel Functional Lung Imaging Technology
Funder
National Health and Medical Research Council
Funding Amount
$891,834.00
Summary
Our team has recently developed a synchrotron technology with a startling capacity for dynamic functional imaging that can act as a sensitive regional indicator of lung disease. We will demonstrate that this technology can be translated from the synchrotron to the lab and eventually the clinic. We will provide proof of this concept by the application of this technology to emphysema, asthma, lung cancer, cystic fibrosis lung disease and neonatal resuscitation.