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
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
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
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
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
Low-temperature plasma processes for high-quality graphene films. The project aims to develop novel plasma-enabled processes for low-cost, energy-efficient, and scalable growth of high-quality graphene films for applications in touch screen, solar cell and other devices. It aims to discover non-equilibrium plasma-surface interactions enabling nucleation and growth of graphene films with large and low-defect domains on metal catalysts at low temperatures, and then develop energy-efficient, enviro ....Low-temperature plasma processes for high-quality graphene films. The project aims to develop novel plasma-enabled processes for low-cost, energy-efficient, and scalable growth of high-quality graphene films for applications in touch screen, solar cell and other devices. It aims to discover non-equilibrium plasma-surface interactions enabling nucleation and growth of graphene films with large and low-defect domains on metal catalysts at low temperatures, and then develop energy-efficient, environment-friendly, and scalable fabrication and device transfer processes. These processes are designed to retain high quality of graphene films upon scale-up and will be compatible with the existing and emerging applications in touch screens and other devices. The expected outcomes include fundamental understanding and novel practical approaches to control synthesis and device integration of two-dimensional atomically-thin materials.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120102942
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
The general Richtmyer-Meshkov instability in magnetohydrodynamics. Fluid dynamic instabilities limit the chance of inertial confinement fusion, a carbon-free process, achieving net energy production. In highly idealised circumstances it has been shown that one of these instabilities can be suppressed by a magnetic field, a phenomenon that this project will investigate in the general case.
The converging shock driven Richtmyer-Meshkov instability in magnetohydrodynamics. Fluid dynamic instabilities limit the chance of inertial confinement fusion, a carbon-free process, achieving net energy production. The project will investigate the effectiveness and consequences of suppressing one of these instabilities with a magnetic field.
Electron scattering and transport for plasma-liquid interactions. The project aims to address the emerging technologies associated with the interaction of plasmas with liquids and biological matter, including plasma medicine. The project expects to generate new knowledge on the role of electron-induced processes through the development of complete and accurate sets of microscopic cross-sections for electrons with biomolecules within tissue. This microscopic data will inform new microscopic model ....Electron scattering and transport for plasma-liquid interactions. The project aims to address the emerging technologies associated with the interaction of plasmas with liquids and biological matter, including plasma medicine. The project expects to generate new knowledge on the role of electron-induced processes through the development of complete and accurate sets of microscopic cross-sections for electrons with biomolecules within tissue. This microscopic data will inform new microscopic models for non-equilibrium electron transport in liquids and biological matter, and its coupling to plasmas. The expected outcomes of this project include progress towards the optimisation of safety/efficacy of future generation plasma medicine devices through detailed understanding of plasma-biological tissue interactions.Read moreRead less
Nanoscale control of energy and matter for future energy-efficient technologies. Unprecedented control of energy and matter in nanoscale fabrication will be achieved using non-equilibrium self-organised plasma-solid systems. The outcomes will lead to energy-efficient, environment- and human-health-friendly production of nanomaterials for future energy, health, information, food, water, environmental and security technologies.