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
Modelling The Biology And Transmission Of Influenza Virus - Learning From 1918-19 And Other Outbreaks
Funder
National Health and Medical Research Council
Funding Amount
$114,222.00
Summary
In preparing for a future pandemic of influenza, it is important to learn as much as possible from what happened in the past, particularly from the devastating pandemic of 1918-19. This project will collate detailed information about the spread of influenza in past outbreaks and create a publicly accessible data-base. Mathematical methods will be used to analyse historic and contemporary data, so as to provide better understanding of the spread of influenza, and of the likely effects of social a ....In preparing for a future pandemic of influenza, it is important to learn as much as possible from what happened in the past, particularly from the devastating pandemic of 1918-19. This project will collate detailed information about the spread of influenza in past outbreaks and create a publicly accessible data-base. Mathematical methods will be used to analyse historic and contemporary data, so as to provide better understanding of the spread of influenza, and of the likely effects of social and medical measures for its control. An important theme of the project is to consolidate our knowledge about how past exposure to non-pandemic influenza could provide short-lived protection against any new pandemic, and to explore the implications of this for prevention today. Another theme is to explore the severity of influenza during pandemics, and to identify social and medical factors that might reduce the dose of virus transmitted, or otherwise reduce the severity of infection. The insights from the modeling will also help to identify gaps in knowledge and understanding about the basic biology of influenza, stimulate new research to fill those gaps, and thus offer the prospect of more effective vaccines and treatments for the future control of influenza.Read moreRead less
Deadly Liver Mob: Engaging Aboriginal People In Viral Hepatitis, HIV And Sexual Health Services
Funder
National Health and Medical Research Council
Funding Amount
$848,441.00
Summary
Rates of blood-borne viruses and sexually transmissible infections are high among the Aboriginal and Torres Strait Islander population. A local initiative in western Sydney has trialed a new approach to engagement and care of Aboriginal people. We will implement this approach in services across NSW and evaluate its effectiveness as a sustainable and acceptable model for engaging Aboriginal people in care and develop an implementation plan for future roll-out to other services.
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
Arbovirus Activation And Modulation Of NLRP3 Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$779,720.00
Summary
This project aims to establish how mosquito borne viruses such as Ross River and dengue viruses interacts with the human host to cause disease, including how the virus evades the host’s immune response to persist and cause disease for prolonged periods. Knowing how differences in the virus and the host’s immune system interplay to cause asymptomatic to severely disabling disease will assist in devising new treatments and prevention programs to lessen the impact of these diseases in Australia.
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
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
Bright x-ray beams from laser-driven microplasmas. This project aims to develop a new generation of bright, laser-like x-ray sources for laboratory use. X-ray sources underpin key diagnostic techniques in materials science, advancing applications from structural engineering through to ore processing and energy storage. However, the limited brightness of present-day laboratory x-ray sources restricts the utility and range of these diagnostic techniques. This research intends to use intense lasers ....Bright x-ray beams from laser-driven microplasmas. This project aims to develop a new generation of bright, laser-like x-ray sources for laboratory use. X-ray sources underpin key diagnostic techniques in materials science, advancing applications from structural engineering through to ore processing and energy storage. However, the limited brightness of present-day laboratory x-ray sources restricts the utility and range of these diagnostic techniques. This research intends to use intense lasers to create microscopic plasmas and drive high harmonic generation. The high harmonic generation process is already used to create laser-like ultraviolet light. By optimising the characteristics of the plasma medium, the project aims to extend bright high harmonic generation to the x-ray regime.Read moreRead less