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Determining Fundamental Mechanisms Compromised In Kir-linked Disease States
Funder
National Health and Medical Research Council
Funding Amount
$600,040.00
Summary
The human nervous system and organs are reliant on precisely controlled transmission of electrical currents through sodium and potassium channels. Their core functions are compromised when currents fail to switch on and off normally. Faulty potassium channels are implicated in diabetes, epilepsy and heart failure. This project re-examines the mechanisms controlling potassium channels, with a view to scientific and therapeutic discrimination between the different classes present in human cells.
Behavioural responses to transport congestion: peak spreading and the more efficient usage of transport infrastructure. Transport networks in cities such as Sydney are at or near capacity. It is no longer socially, environmentally or financially sustainable to continue supplying additional transport infrastructure to meet increased demand. An alternative is to make better use of existing infrastructure by spreading demand more evenly across the day. This project will test behavioural responses t ....Behavioural responses to transport congestion: peak spreading and the more efficient usage of transport infrastructure. Transport networks in cities such as Sydney are at or near capacity. It is no longer socially, environmentally or financially sustainable to continue supplying additional transport infrastructure to meet increased demand. An alternative is to make better use of existing infrastructure by spreading demand more evenly across the day. This project will test behavioural responses to increased congestion and quantify the phenomenon of peak spreading. It will assess economic costs and benefits of using congestion as a signal to encourage more efficient network usage, and examine other tools (e.g. time-based transport pricing) to encourage more efficient use of transport infrastructure.Read moreRead less
Multidimensional evaluation of the overall benefits of voluntary travel behaviour change programs. Voluntary Travel Behaviour Programs (VTBC) offer considerable promise for the management of traffic congestion and reduction in greenhouse gas and air quality emissions from road transport. Research to date has identified two outstanding issues: (1) measurement and evaluation of actual behaviour change and (2) identification of the full benefits and impacts of VTBC. Empirical studies indicate that ....Multidimensional evaluation of the overall benefits of voluntary travel behaviour change programs. Voluntary Travel Behaviour Programs (VTBC) offer considerable promise for the management of traffic congestion and reduction in greenhouse gas and air quality emissions from road transport. Research to date has identified two outstanding issues: (1) measurement and evaluation of actual behaviour change and (2) identification of the full benefits and impacts of VTBC. Empirical studies indicate that many of the benefits fall outside the transport area, including a wide range of socio-economic benefits to individuals and the community. This project will develop a survey tool for assessing benefits and impacts of VTBC within a properly designed and tested evaluation framework.Read moreRead less
Promoting active travel and public transport for a post-pandemic world. In many major cities, COVID-19 stimulated the provision of open streets, pop up bike lanes and widened pedestrian access, prompting unprecedented increases cycling and walking. While this type of infrastructure has always been supported by urban planners and designers, the pandemic has served as a vital inflection point, enabling cities to pursue long-term sustainable transport initiatives, including investment in Active Tra ....Promoting active travel and public transport for a post-pandemic world. In many major cities, COVID-19 stimulated the provision of open streets, pop up bike lanes and widened pedestrian access, prompting unprecedented increases cycling and walking. While this type of infrastructure has always been supported by urban planners and designers, the pandemic has served as a vital inflection point, enabling cities to pursue long-term sustainable transport initiatives, including investment in Active Travel (AT). There is an opportunity to promote AT as part of an integrated transport strategy, and to develop tools for the robust evaluation of AT impacts to inform future investment strategies. This proposal will provide our partner organisation Transport for New South Wales (with the knowledge required to achieve this.
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The Role Of Force-sensing Ion Channels In Melanoma Migration
Funder
National Health and Medical Research Council
Funding Amount
$553,848.00
Summary
Metastasis of melanoma cells away from the primary tumour site carries a very poor patient prognosis.This research aims to characterise a novel signalling pathway that can regulate the migration (movement) of melanoma cells. This signalling pathway depends on force-sensing platforms that can rapidly convert physical inputs from the environment into an electrical signal within the cell. We are working to understand how these force-sensors function.
The cells that produce and maintain our cartilage, known as chondrocytes, do so by sensing changes in the mechanical environment, but precisely how chondrocytes detect these changes is not known. We are investigating the role of ion channels that are opened in direct response to mechanical movements within the cartilage.This project plans to identify the specific molecules that are participating in this process and to determine if they are therapeutic targets for treatment of osteoarthritis
Structure-function Studies Of Ion Permeation And Selectivity In Recombinant Glycine Receptor Channels
Funder
National Health and Medical Research Council
Funding Amount
$331,300.00
Summary
Ligand-gated ion channels (LGICs) are members of a superfamily of receptor channels, with very significant structural and functional similarities, which play a major role in fast synaptic neurotransmission within the brain and spinal cord, and underlying the complex behaviour of the nervous system, but when dysfunctional can result in major neurological problems. Glycine is one of the two most important inhibitory neurotransmitters in the central nervous system. Impaired glycine-mediated neurotr ....Ligand-gated ion channels (LGICs) are members of a superfamily of receptor channels, with very significant structural and functional similarities, which play a major role in fast synaptic neurotransmission within the brain and spinal cord, and underlying the complex behaviour of the nervous system, but when dysfunctional can result in major neurological problems. Glycine is one of the two most important inhibitory neurotransmitters in the central nervous system. Impaired glycine-mediated neurotransmission underlies a range of inherited neurological diseases and already, it has been shown that the human disorder, familial Startle disease (hyperekplexia) occurs because of point mutations that have impaired the permeation and activation of the glycine receptor (GlyR). Similarly, certain epilepsies are now known to be caused by mutations in, or close to, the channel region in the excitatory acetylcholine receptors (AChRs), which affect channel activation and ion permeation. However, because of their very significant structural and functional similarities, information obtained in one member of the LGIC family of receptors has strong potential application to the other members and the GlyR with its simpler structure has certain advantages for investigation. The first aim of this project is to investigate how the molecular biological structure of these ion channels controls permeation, how it affects how different ions are selectively allowed to move through it and how it affects channel activation. A second related aim is to learn more about the process of desensitization of GlyR receptors, whereby a sustained presence of a high concentration of agonist can cause a reduction in receptor response. A third aim is to specifically investigate the mechanisms underlying the mode of molecular disruption resulting from two new Startle disease mutations, which, in addition to their own inherent clinical value, can also give general information about receptor function.Read moreRead less
Prediction and control of fluid-structure interactions. Fluid-flows create a pressure that can deform the surface of a structure or cause it to vibrate; an extreme example is the fluttering of a flag. Flow-induced vibration of the external panels of vehicles causes damage, noise and can adversely affect performance. This project will develop a wholly new approach for the analysis of these interactions. The versatility and completeness of the approach permits a step-change in the design of panels ....Prediction and control of fluid-structure interactions. Fluid-flows create a pressure that can deform the surface of a structure or cause it to vibrate; an extreme example is the fluttering of a flag. Flow-induced vibration of the external panels of vehicles causes damage, noise and can adversely affect performance. This project will develop a wholly new approach for the analysis of these interactions. The versatility and completeness of the approach permits a step-change in the design of panels, reducing material and manufacturing costs without compromise to safety and performance - an immense benefit for the myriad engineered products or structures that feature flow over a deformable surface. Read moreRead less
Taming turbulence: Hydrodynamic stability and flow-structure interaction using grid-free computation. Turbulence is characterized as seemingly disordered fluctuations that impede the progress of an object through a fluid by creating increased frictional or drag forces. Using a new type of fluid-flow simulation, this project will generate advanced understanding of turbulence in the flow over the surface of a vehicle, be it a ship, car, aircraft or within a pipe, with the technological objective o ....Taming turbulence: Hydrodynamic stability and flow-structure interaction using grid-free computation. Turbulence is characterized as seemingly disordered fluctuations that impede the progress of an object through a fluid by creating increased frictional or drag forces. Using a new type of fluid-flow simulation, this project will generate advanced understanding of turbulence in the flow over the surface of a vehicle, be it a ship, car, aircraft or within a pipe, with the technological objective of reducing drag by adhering a compliant skin to the surface. While the correct choice of compliance relies upon understanding very complex flow-structure dynamics, the resulting technology is simple, robust and has low capital and maintenance costs. Clearly, drag reduction reduces fuel costs and lower fuel consumption is environmentally beneficial. Read moreRead less