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
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
Non-equilibrium presolvation electron processes at the gas-liquid interface. The interaction of low-temperature plasma electrons with liquids has served as a reducing agent in various technological applications in water treatment, agriculture, biofuels and medicine. Predictive control of the plasma-liquid interface is essential to unlocking the potential of these applications, and this has been limited by the absence of the relevant non-equilibrium transport theory describing electrons at the pl ....Non-equilibrium presolvation electron processes at the gas-liquid interface. The interaction of low-temperature plasma electrons with liquids has served as a reducing agent in various technological applications in water treatment, agriculture, biofuels and medicine. Predictive control of the plasma-liquid interface is essential to unlocking the potential of these applications, and this has been limited by the absence of the relevant non-equilibrium transport theory describing electrons at the plasma-liquid interface together with fundamental data describing electron interactions with liquids. The project will develop a state of the art presolvation electron transport model informed by world first measurements of electron cross-sections for radicals and liquids and apply it to model plasma electrochemistry processes.Read moreRead less
Advanced materials for space propulsion: satellites and cubesats. Poorly controlled interactions between plasmas and surfaces often mean loss of process efficiency and surface degradation over time. For Hall thrusters, a type of engine used to move satellites in space, this means increased fuel consumption and shorter useful life. Through modelling and experiment, this project will show how intelligent selection of advanced materials and plasma parameters can minimise surface wear, enable in sit ....Advanced materials for space propulsion: satellites and cubesats. Poorly controlled interactions between plasmas and surfaces often mean loss of process efficiency and surface degradation over time. For Hall thrusters, a type of engine used to move satellites in space, this means increased fuel consumption and shorter useful life. Through modelling and experiment, this project will show how intelligent selection of advanced materials and plasma parameters can minimise surface wear, enable in situ material repair to extend device lifetime, and modulate plasma properties to increase thruster efficiency for a given task. These benefits enable reliable propulsion platforms for massive communication and observation satellite networks and deep space exploration.Read moreRead less
Development of solvent extraction systems for improved sugar quality and yield. The recent collapse in the international sugar price and increased competition amongst producers have highlighted the vulnerability of Australian sugar mills and the regional communities reliant on sugar cane growing to variation in the price of this commodity. Hence, the development of new, more efficient means to produce raw sugar of high quality is of paramount importance to maintain Australia as a low cost produ ....Development of solvent extraction systems for improved sugar quality and yield. The recent collapse in the international sugar price and increased competition amongst producers have highlighted the vulnerability of Australian sugar mills and the regional communities reliant on sugar cane growing to variation in the price of this commodity. Hence, the development of new, more efficient means to produce raw sugar of high quality is of paramount importance to maintain Australia as a low cost producer. This project aims to investigate the use of unique solvent extraction methods to remove deleterious impurities from the raw cane juice in sugar mills with the consequent improvement in both sugar yield and quality.Read moreRead less
Deciphering Signalling Pathways Regulating Iron Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$407,402.00
Summary
Iron overload and anaemia are two of the most significant health problems affecting humans. Understanding how the body regulates iron levels is key to our understanding of these disorders and to the future development of new therapies. This research is aimed at understanding how a hormone produced in the liver called hepcidin that maintains iron balance is regulated. This research may lead to novel therapies aimed at correcting the iron balance in conditions of iron overload or anaemia.
Mechanosensitive properties and modulation of N-methyl-D-aspartate (NMDA) receptors by lipid environment. This project will provide new information about the molecular determinants which influence NMDA receptor channel gating that will significantly advance our understanding of a link between NMDA receptor function and many neurodegenerative diseases as well as pain and learning and memory. The outcomes of this project may lead to the discovery of novel lipid-based biomaterials for application i ....Mechanosensitive properties and modulation of N-methyl-D-aspartate (NMDA) receptors by lipid environment. This project will provide new information about the molecular determinants which influence NMDA receptor channel gating that will significantly advance our understanding of a link between NMDA receptor function and many neurodegenerative diseases as well as pain and learning and memory. The outcomes of this project may lead to the discovery of novel lipid-based biomaterials for application in medicine and the drug industry. This research is highly significant in relation to human health. The biological and nutritional aspects of polyunsaturated lipids and dietary fish oils have long been recognized. Thus this project will provide further knowledge that could benefit the health of the nation with consequent reduced health care costs.Read moreRead less
Plasma-assisted on-surface assembly for hydrogen production and beyond. This project aims to discover how to catalyse the formation and control the structure of functional materials with atomic precision using plasmas. New mechanisms of ultra-fast, plasma-catalytic on-surface nanoasembly will translate into energy-efficient, scalable digital fabrication of subnano-cluster and single-atomic-site catalysts over large 3D surface areas, tailored for advanced electrocatalysis. The outcomes including ....Plasma-assisted on-surface assembly for hydrogen production and beyond. This project aims to discover how to catalyse the formation and control the structure of functional materials with atomic precision using plasmas. New mechanisms of ultra-fast, plasma-catalytic on-surface nanoasembly will translate into energy-efficient, scalable digital fabrication of subnano-cluster and single-atomic-site catalysts over large 3D surface areas, tailored for advanced electrocatalysis. The outcomes including new concepts and insights into synergistic action of plasmas and solid surfaces will bridge atomic-scale materials formation and digital fabrication at industrial scales. The benefits including the new nanofabrication platform and clean energy will go beyond the demands of digital manufacturing and hydrogen economy. Read moreRead less
Methane Coupling Using Mixed Conducting Catalytic Ceramic Hollow Fibre Membrane Reactor. The Gas product industry is one of the most important economic sectors in Australia, employing 10000 people with market value of $ 100 billion per year from power generation and LNG export. However, there are increasing concerns over issues of the green house gases emission and petroleum dwindling. This project addresses the technology needs in converting natural gas to more useful chemicals via a more effic ....Methane Coupling Using Mixed Conducting Catalytic Ceramic Hollow Fibre Membrane Reactor. The Gas product industry is one of the most important economic sectors in Australia, employing 10000 people with market value of $ 100 billion per year from power generation and LNG export. However, there are increasing concerns over issues of the green house gases emission and petroleum dwindling. This project addresses the technology needs in converting natural gas to more useful chemicals via a more efficient and cleaner means of methane utilization. The project target is to make the natural gas resources in Australia to delivery high value products with considerable economic benefits and increased employment opportunities. Read moreRead less