Insulin resistance (the inability of ordinarily insulin-sensitive tissues such as muscle and adipose tissue to respond to insulin) contributes to a number of diseases including diabetes and obesity. A key metabolic step in these tissues is the uptake of glucose from the blood stream. This step is accelerated by insulin thus allowing efficient clearance of glucose from the bloodstream after a meal. Our laboratory has played a major role in showing that insulin regulates glucose uptake into muscle ....Insulin resistance (the inability of ordinarily insulin-sensitive tissues such as muscle and adipose tissue to respond to insulin) contributes to a number of diseases including diabetes and obesity. A key metabolic step in these tissues is the uptake of glucose from the blood stream. This step is accelerated by insulin thus allowing efficient clearance of glucose from the bloodstream after a meal. Our laboratory has played a major role in showing that insulin regulates glucose uptake into muscle and adipose tissue by stimulating the movement of a glucose transport protein from inside the cell to the cell surface (see http:--www.imb.uq.edu.au-groups-james-glut4 for an animated description of this process). The purpose of this proposal is to dissect the molecular mechanisms by which this glucose transporter can be held inside the cell in the absence of insulin and then allowed to be released from this site moving to the surface in the presence of insulin. Our studies over the past 5 years have brought us much closer to understanding this process in detail. The identification of the molecules responsible for this regulatory step will not only aid our understanding of this process but it will also provide a valuable target for development of therapeutic agents that can be used to combat insulin resistance.Read moreRead less
Mechanism Of Action Of Sec1p-like Proteins In Membrane Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$234,936.00
Summary
One of the most important evolutionary changes that has occurred is the development of intracellular compartments. All eukaryotic cells possess numerous membrane-encased structures which provide the basis for intracellular specialisation. For example, in order to degrade unwanted components cells have developed degradative enzymes. It is vital for the cell that these enzymes are sequestered away from other cellular components to avoid destruction of valuable molecules. In addition, the cell has ....One of the most important evolutionary changes that has occurred is the development of intracellular compartments. All eukaryotic cells possess numerous membrane-encased structures which provide the basis for intracellular specialisation. For example, in order to degrade unwanted components cells have developed degradative enzymes. It is vital for the cell that these enzymes are sequestered away from other cellular components to avoid destruction of valuable molecules. In addition, the cell has developed a complex assembly line of modifications that are added to proteins in a specific order as they travel to their final destination within the cell. This necessitates the accurate passage of molecules between compartments, a process known as vesicle transport. To orchestrate the complex network of vesicular transport steps between all of the various intracellular compartments it is necessary to employ complex machinery to guide and check that these steps occur with high fidelity. The goal of our research proposal is to define the function of one of the molecules involved in this control process, the so-called Sec1p proteins. The strength of our proposal lies in the diversity of our approach. We intend to explore the molecular advantages of a relatively simple eukaryotic organism, a yeast cell, and apply the findings obtained from this cell to a more complex but highly related vesicular transport process; that of the insulin-regulated movement of a glucose transporter in mammalian fat and muscle cells. While we intend to apply our findings to the treatment of patients with diabetes, it is our ultimate goal to be able to learn more about this fundamental cell biological process so that we can apply our knowledge to understanding many different disease states.Read moreRead less
Macrophages are white blood cells that provide front line defence against infection by initiating inflammatory responses by ingesting or phagocytosing microbes and by releasing soluble messengers (cytokines) to recruit other immune cells. These defensive functions require extensive trafficking of proteins within the macrophages. Protein trafficking is orchestrated in part by a family of membrane fusion proteins called SNAREs. By defining the relevant SNAREs, we have recently discovered a much ac ....Macrophages are white blood cells that provide front line defence against infection by initiating inflammatory responses by ingesting or phagocytosing microbes and by releasing soluble messengers (cytokines) to recruit other immune cells. These defensive functions require extensive trafficking of proteins within the macrophages. Protein trafficking is orchestrated in part by a family of membrane fusion proteins called SNAREs. By defining the relevant SNAREs, we have recently discovered a much acclaimed and novel pathway that allows efficient, combined cytokine secretion and phagocytosis in macrophages. Our studies proposed here will now expand on this discovery by comparing the phagocytic process, in terms of SNARE-mediated membrane and cytokine trafficking, for a wide range of microbes, highlighting differences that could provide new avenues for drug development. Moreover, since our strategy of using SNAREs to investigate and map trafficking pathways has proven so successful, we will now launch a major large-scale initiative to study ALL SNARE-mediated trafficking pathways in macrophages using a discovery pipeline of assays, including live cell imaging, we have developed. This will provide valuable information on many SNAREs including those associated with disease, and will elucidate trafficking pathways governing all macrophage actions in immunity, including cytokine secretion and antigen presentation. All of these pathways are highly relevant to current drug targets being used clinically or studied in inflammatory disease and for the development of vaccines.Read moreRead less
Regulating The Secretion Of Inflammatory Cytokines
Funder
National Health and Medical Research Council
Funding Amount
$558,441.00
Summary
Cytokines or chemical messengers released by cells are essential for controlling immune responses but, in excess, they cause Crohn's disease and arthritis. Our research aims to block cytokine release as a novel way to ameliorate disease. We have identified specific cellular proteins, called golgins, that can be targeted to reduce cytokines. Here, characterization of golgin mediated cytokine transport in cells and in a mouse disease model is necessary to translate these findings for human benefit
Monitoring and Maintaining the Structural Health of Bridges Using Vibration Characteristics. Bridges form an important part of our physical infrastructure system and in Queensland alone there are nearly 3000 bridges with an annual maintenance cost in excess of 20 million dollars and a replacement value in excess of 2 billion dollars. It is necessary to ensure that these bridges function safely and efficiently at all times. Bridge failure will cause disruption to normal lives and expensive repa ....Monitoring and Maintaining the Structural Health of Bridges Using Vibration Characteristics. Bridges form an important part of our physical infrastructure system and in Queensland alone there are nearly 3000 bridges with an annual maintenance cost in excess of 20 million dollars and a replacement value in excess of 2 billion dollars. It is necessary to ensure that these bridges function safely and efficiently at all times. Bridge failure will cause disruption to normal lives and expensive repairs. Towards this end, this project will develop an innovative structural health monitoring system to monitor and maintain the structural health of our bridges. The project outcomes will have immediate applications in Australia and overseas with economic and social benefits to the community.Read moreRead less
Optimisation of Rail Network Infrastructure Capacity under Dynamic Train Planning. Recent changes in railway operating environments have caused significant operational and management problems in Australia. This research will lead to improvements of railway's key managerial functions, namely: network capacity planning; rollingstock planning; train scheduling; and maintenance planning. The major outcome of the research will be to develop an optimisation model to significantly improve the operati ....Optimisation of Rail Network Infrastructure Capacity under Dynamic Train Planning. Recent changes in railway operating environments have caused significant operational and management problems in Australia. This research will lead to improvements of railway's key managerial functions, namely: network capacity planning; rollingstock planning; train scheduling; and maintenance planning. The major outcome of the research will be to develop an optimisation model to significantly improve the operating efficiency and assets productivity of Australia's rail system. The novelty of the research is that it will be undertaken using innovations based on modern job shop scheduling and sequencing optimisation techniques as the complexity of the problem makes it impossible to solve by classic optimisation techniques.Read moreRead less
Wave Climate in the Southern Great Barrier Reef. Sea surface roughness has a major influence on global climate modelling. This project will provide a better understanding of the variability of sea waves in coastal waters. New technology of HF ocean radar can map wave fields over coastal waters and thus fill a gap between the open ocean satellite measurements and the point measurements from wave buoys. In this project we will improve the analysis of the radar echoes to produce sea wave spectra, a ....Wave Climate in the Southern Great Barrier Reef. Sea surface roughness has a major influence on global climate modelling. This project will provide a better understanding of the variability of sea waves in coastal waters. New technology of HF ocean radar can map wave fields over coastal waters and thus fill a gap between the open ocean satellite measurements and the point measurements from wave buoys. In this project we will improve the analysis of the radar echoes to produce sea wave spectra, and evaluate focussing of waves by complex currents on the continental shelf to help improve wave forecasting in coastal waters. The HF radar will be used to experimentally test current theories of wind wave spreading.Read moreRead less
Assessing the full impacts of high efficiency heavy vehicles in urban traffic networks using new analytical tools. Significant economic benefits result from new innovative heavy vehicles, which are able to carry up to twice the payload of standard semi-trailers. In addition, those vehicles have the potential to reduce overall accidents and evironmental degradation. Those benefits need to be traded-off against the impacts on other road users. This research will improve the operation of such ve ....Assessing the full impacts of high efficiency heavy vehicles in urban traffic networks using new analytical tools. Significant economic benefits result from new innovative heavy vehicles, which are able to carry up to twice the payload of standard semi-trailers. In addition, those vehicles have the potential to reduce overall accidents and evironmental degradation. Those benefits need to be traded-off against the impacts on other road users. This research will improve the operation of such vehicles in regional centres by producing: (1) an assessment methodology to deal with options for network efficiency gains which will capture the full impacts; and (2) a computer modelling tool based on fundamental research to quantify those impacts, in terms of delays and accident rates.Read moreRead less
Special Research Initiatives - Grant ID: SR0354488
Funder
Australian Research Council
Funding Amount
$10,000.00
Summary
Intelligent vehicles and road infrastructure (IVRI). The aims of the network are to integrate the activities of researchers and practitioners in the areas of vehicles and road infrastructure and through cross-disciplinary collaboration apply intelligent control systems to deliver mobility, which is safer for all users, reduces driver stress and environmental impact with increased local manufactured content and improved cost effectiveness. It is of great significance to provide a cohesive solutio ....Intelligent vehicles and road infrastructure (IVRI). The aims of the network are to integrate the activities of researchers and practitioners in the areas of vehicles and road infrastructure and through cross-disciplinary collaboration apply intelligent control systems to deliver mobility, which is safer for all users, reduces driver stress and environmental impact with increased local manufactured content and improved cost effectiveness. It is of great significance to provide a cohesive solution to the transport problem considering all modes, environmental impacts, and economical and social considerations. This project should lead to a report identifying Australia's capability in this sector and a roadmap for a future research network integrating university and industry based research.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE130100205
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Optimisation of transit priority in a transportation network. This project is aimed at developing an optimised approach to combine various types of public transport priority in an urban network which can be used by transport planners to increase the efficiency of traffic movements and reduce traffic congestion. The case study is the network of Brisbane including all arterial and local roads.