Visualising vascular adaptation at the micro-scale in humans. The project aims to investigate fundamental issues in the mechanisms underlying vascular remodelling. It plans to develop novel optical scanning techniques to acquire high-resolution images of the cutaneous microvasculature, alongside absolute blood flow quantification. These novel tools would allow us to visualise and quantify functional and structural adaptations in the microvasculature in response to physiological stimuli such as h ....Visualising vascular adaptation at the micro-scale in humans. The project aims to investigate fundamental issues in the mechanisms underlying vascular remodelling. It plans to develop novel optical scanning techniques to acquire high-resolution images of the cutaneous microvasculature, alongside absolute blood flow quantification. These novel tools would allow us to visualise and quantify functional and structural adaptations in the microvasculature in response to physiological stimuli such as heat exposure and exercise. The non-invasive tool aims to enable us to assess adaptations in microvasculature health, improving our understanding of cardiovascular diseases and type 2 diabetes and potentially reducing the impact of costly and debilitating morbidities such as nephropathy, neuropathy, retinopathy, impotence and skin ulceration.Read moreRead less
A microfluidic approach to study the mechanobiology of ageing blood vessels. This project aims to study the effect of the stiffening of ageing arteries in endothelial cells. It explores the changes that occur in endothelial cells using a unique microfluidic technology with tuneable wall stiffness to mimic the biophysical and biochemical properties of ageing arteries. The expected outcome is the identification of the cellular mechanisms that control endothelial responses to arterial stiffening. T ....A microfluidic approach to study the mechanobiology of ageing blood vessels. This project aims to study the effect of the stiffening of ageing arteries in endothelial cells. It explores the changes that occur in endothelial cells using a unique microfluidic technology with tuneable wall stiffness to mimic the biophysical and biochemical properties of ageing arteries. The expected outcome is the identification of the cellular mechanisms that control endothelial responses to arterial stiffening. This should provide the fundamental knowledge required to assist in the development of new therapies to tackle age-related conditions such as cardiovascular disease and dementia.Read moreRead less
Molecular Interactions of Chemical Agents with Ion-Channel Proteins. With a minimal number of functional units (proteins) viruses are able to replicate. All of these proteins are possible antiviral targets. In this project we wil1 focus on a short protein called Vpu found in membranes of the HIV-1 virus and aim to analyse the interaction of potential pore blocking compounds. It is essential to know exactly where they sit and how the overall structure of Vpu is affected. For this enterprise we wi ....Molecular Interactions of Chemical Agents with Ion-Channel Proteins. With a minimal number of functional units (proteins) viruses are able to replicate. All of these proteins are possible antiviral targets. In this project we wil1 focus on a short protein called Vpu found in membranes of the HIV-1 virus and aim to analyse the interaction of potential pore blocking compounds. It is essential to know exactly where they sit and how the overall structure of Vpu is affected. For this enterprise we will use nuclear magnetic resonance (NMR) spectroscopy. This information will serve as a springboard for future investigations of virus membrane proteins.
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Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775660
Funder
Australian Research Council
Funding Amount
$500,000.00
Summary
A National Biomedical Electron Paramagnetic Resonance and Molecular Imaging Centre. Multifrequency continuous wave and pulsed electron paramagnetic resonance spectroscopy and molecular imaging instrumentation will provide forefront technologies in identifying, characterising, quantifying, visualising and manipulating fundamental chemical and biologically relevant processes involving free radicals, metalloproteins and metal ions. This technology is crucial in validating these functional processes ....A National Biomedical Electron Paramagnetic Resonance and Molecular Imaging Centre. Multifrequency continuous wave and pulsed electron paramagnetic resonance spectroscopy and molecular imaging instrumentation will provide forefront technologies in identifying, characterising, quantifying, visualising and manipulating fundamental chemical and biologically relevant processes involving free radicals, metalloproteins and metal ions. This technology is crucial in validating these functional processes at the cellular and tissue level and for providing invaluable and unique biomedical information under physiological conditions. This synergistic and highly integrative approach will make available new techniques for identifying major disease mechanisms such as cardiovascular disease with a potential to improve and maintain health. Read moreRead less
Electric field induced surface attachment and detachment of proteins. Microarrays are revolutionising the diagnosis of disease by enabling large amounts of data on genetics and protein expression to be obtained from one sample. Biosensors for diseases and toxins rely on the same mechanism, namely attachment of biological macromolecules to a surface. We propose a new method for controlling the attachment by micromachining an electrode system to apply an electric field to chosen sites. Ultimately ....Electric field induced surface attachment and detachment of proteins. Microarrays are revolutionising the diagnosis of disease by enabling large amounts of data on genetics and protein expression to be obtained from one sample. Biosensors for diseases and toxins rely on the same mechanism, namely attachment of biological macromolecules to a surface. We propose a new method for controlling the attachment by micromachining an electrode system to apply an electric field to chosen sites. Ultimately microelectronic engineering methods will be used. This will give control over the attachment process with potential benefits of orienting attaching molecules, minimising non-specific attachment and enriching diagnostics by enabling interrogation of the force of attachment.Read moreRead less
Sinusoidal voltage protocols for characterisation of ion channel kinetics. This project aims to implement an innovative approach to modelling ion channel behaviour that employs short, information-rich datasets and parameter inference. Using the hERG potassium channel as a test case, the project will show that this approach is more efficient than current methods and outperforms all published models in independent validations. The project aims to extend on initial implementation to probe the therm ....Sinusoidal voltage protocols for characterisation of ion channel kinetics. This project aims to implement an innovative approach to modelling ion channel behaviour that employs short, information-rich datasets and parameter inference. Using the hERG potassium channel as a test case, the project will show that this approach is more efficient than current methods and outperforms all published models in independent validations. The project aims to extend on initial implementation to probe the thermodynamics and pharmacology of ion channel gating. The anticipated outcomes are to grow fundamental knowledge of ion channel biophysics and ability to probe ion channel function in silico. The project will build on an emerging collaboration between international leaders in physiology, pharmacology, mathematics and computer modelling. The methodology and fundamental knowledge generated will significantly advance our understanding of the physiology and biophysics of ion channels, while the application of the method will have direct impact in the pharmaceutical industry and regulatory science.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE130101393
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Neurobiological mechanisms of decision under uncertainty. The purpose of this project is to understand the behavioural and brain mechanisms underlying decision under uncertainty. This research will uncover the effect that normal variation in brain networks has on choice and contribute to a better understanding of disorders linked to intolerance of uncertainty.
The Bcl-2 family of proteins is crucial for apoptosis (a form of programmed cell death) regulation. They target the mitochondrial outer membrane where they interact to determine cell fate. We will evaluate the membrane interactions of the Bcl-2 proteins in complementary biophysical and cellular experiments to redefine our understanding of the mechanism of apoptosis and provide new avenues for the development of compounds to selectively modulate diseases in which apoptosis is unregulated.