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
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
Beyond linear source-filter theory: how does the vocal tract affect the motion of the vocal folds? The human voice lies at the very core of human culture. Yet the way in which the vocal folds ('vocal cords') vibrate is only partly understood and the way in which sound waves within the vocal tract affect this vibration is almost unknown, beyond the fact that it is sometimes important. Using new and unique non-invasive techniques, we shall conduct acoustic experiments to measure properties of the ....Beyond linear source-filter theory: how does the vocal tract affect the motion of the vocal folds? The human voice lies at the very core of human culture. Yet the way in which the vocal folds ('vocal cords') vibrate is only partly understood and the way in which sound waves within the vocal tract affect this vibration is almost unknown, beyond the fact that it is sometimes important. Using new and unique non-invasive techniques, we shall conduct acoustic experiments to measure properties of the vocal folds and their interaction with the sound they produce in the vocal tract. This knowledge will solve some of the remaining puzzles about the voice. Practical applications will include exercises in voice control (especially for singers and orators) and potential applications in clinical diagnosis techniques.Read moreRead less
Verification of a theoretical model of the dynamical genesis of brain electrical activity. The physiological basis for the rhythmic scalp electrical activity known as the alpha rhythm has remained elusive despite being first recorded over eighty years ago. However, one of the applicants (DTJL) has developed a novel theory of the electroencephalogram (EEG) that theoretically articulates the necessary physiological conditions required for the genesis of this activity that is subject to rigorous e ....Verification of a theoretical model of the dynamical genesis of brain electrical activity. The physiological basis for the rhythmic scalp electrical activity known as the alpha rhythm has remained elusive despite being first recorded over eighty years ago. However, one of the applicants (DTJL) has developed a novel theory of the electroencephalogram (EEG) that theoretically articulates the necessary physiological conditions required for the genesis of this activity that is subject to rigorous experimental test. Empirical verification of this theory will pave the way to elucidating the functional importance of large scale brain electrical activity in neural information processing as well as enabling the rational use of the EEG for drug design and diagnosis.Read moreRead less
Multiscale and multimodal modelling of brain dynamics. This project aims to understand dynamics of how several brain regions work together to process information. This project will generate new knowledge in brain sciences by using state of the art computational modelling and neuroimaging methods like functional and diffusion magnetic resonance imaging and electromagnetic measurements. This project will develop technologies to compute multiscale, multimodal and directed connectivity in the brain. ....Multiscale and multimodal modelling of brain dynamics. This project aims to understand dynamics of how several brain regions work together to process information. This project will generate new knowledge in brain sciences by using state of the art computational modelling and neuroimaging methods like functional and diffusion magnetic resonance imaging and electromagnetic measurements. This project will develop technologies to compute multiscale, multimodal and directed connectivity in the brain. Expected outcomes of this project will enhance our understanding of the brain’s functional organization and dynamics. The benefits of this project will include breakthroughs in development of new neuro-technologies like brain-machine interfaces and neuroscience inspired artificial intelligence. Read moreRead less
Understanding aerobic respiration: Models for the catalytic centre in proton-pumping heme-copper oxidases. This project tackles ?head on? a key challenge in contemporary biological inorganic chemistry, understanding how at the atomic level aerobic life uses oxygen. All life we see is aerobic, and thus the conceptual advances from this research will progress understanding of our world and ourselves? an important cultural goal. Advancing knowledge of such fundamental processes sits firmly in the a ....Understanding aerobic respiration: Models for the catalytic centre in proton-pumping heme-copper oxidases. This project tackles ?head on? a key challenge in contemporary biological inorganic chemistry, understanding how at the atomic level aerobic life uses oxygen. All life we see is aerobic, and thus the conceptual advances from this research will progress understanding of our world and ourselves? an important cultural goal. Advancing knowledge of such fundamental processes sits firmly in the area of the Research Priority Goal: Breakthrough Science. Postgraduate research students will be trained in sophisticated state-of-the-art theoretical and synthetic chemical methodologies. The project will enhance Australia's research capability in biological (inorganic) chemistry and promote Australia's standing in the International research community.Read moreRead less
Biomolecular activity modulated by interaction with nanostructures. Nanotechnological methods are able to reliably fabricate artificial nanostructures with dimensions similar to those of large biomolecules (a few to tens of nanometers). This study focuses on the interaction of artificial nanostructures with biomolecules such as proteins and DNA, and will enable scientists to better understand biomolecular recognition and binding events, which are central to all biological processes. The underst ....Biomolecular activity modulated by interaction with nanostructures. Nanotechnological methods are able to reliably fabricate artificial nanostructures with dimensions similar to those of large biomolecules (a few to tens of nanometers). This study focuses on the interaction of artificial nanostructures with biomolecules such as proteins and DNA, and will enable scientists to better understand biomolecular recognition and binding events, which are central to all biological processes. The understanding gained can then be used to design biomimetic surfaces for use in health monitoring and medical diagnostic devices with improved sensitivity, robustness and portability, thereby providing significant benefits to the health sector.Read moreRead less
Physiology of oxygen transport in the mammalian kidney. This project aims to improve understanding of oxygen regulation in renal tissue and knowledge of the physiology of the kidney. The mammalian kidney receives more oxygen than it uses or needs, and yet renal tissue is commonly found to be hypoxic. This project proposes that oxygen transport to the renal tissue is limited by blood vessel surface area. The project expects to generate anatomical data currently missing from the renal physiology c ....Physiology of oxygen transport in the mammalian kidney. This project aims to improve understanding of oxygen regulation in renal tissue and knowledge of the physiology of the kidney. The mammalian kidney receives more oxygen than it uses or needs, and yet renal tissue is commonly found to be hypoxic. This project proposes that oxygen transport to the renal tissue is limited by blood vessel surface area. The project expects to generate anatomical data currently missing from the renal physiology community, and potentially change the accepted story of oxygen homeostasis in the kidney. This will provide significant benefits, such as the provision of the foundational physiological science behind a determinant of kidney health and its flow-on impact to quality of life.Read moreRead less