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
$440,250.00
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
The Molecular Mechanism Of Ion-coupled Transport In The Brain
Funder
National Health and Medical Research Council
Funding Amount
$441,407.00
Summary
Cells in the brain communicate through chemical signals called neurotransmitters. Neurotransmitter transporters reside in the membranes of cells and are responsible for regulating levels of these chemicals in the brain. They play an important role in the normal function of the human brain but their dysfunction is responsible for many diseases including Alzheimer's disease and motor neuron disease. It is crucial to understand how these proteins work in both normal and disease states.
Integrated Observation, Theory, and Simulation of Type II Solar Radio Bursts. Type II solar radio bursts are associated with solar flares, coronal mass ejections (CMEs), and space weather events at Earth. They are the archetype of collective radio emission associated with shocks. This project aims to: answer longstanding fundamental scientific questions about type IIs using the new Murchison Widefield Array (MWA) and NASA spacecraft, while developing a new Australian capability in solar radio ph ....Integrated Observation, Theory, and Simulation of Type II Solar Radio Bursts. Type II solar radio bursts are associated with solar flares, coronal mass ejections (CMEs), and space weather events at Earth. They are the archetype of collective radio emission associated with shocks. This project aims to: answer longstanding fundamental scientific questions about type IIs using the new Murchison Widefield Array (MWA) and NASA spacecraft, while developing a new Australian capability in solar radio physics; perform new observations and theoretical calculations of relevant emission mechanisms, and, develop a new integrated data-tested theory and simulation capability for type II bursts that explains the emissions quantitatively, and positions us to predict the arrival of CMEs and related space weather at Earth. Read moreRead less
Biomaterials with multifaceted tunability and bio-specificity. Polyurethanes, a family of polymers with independently tunable mechanical and biodegradation properties, will be developed as a versatile platform material for biomedical implants. Novel energetic ion treatments that allow the coupling of bioactive agents to surfaces will eliminate adverse reactions and enable integration with surrounding tissue.
New generation pulsed magnetron sputtering for the synthesis of advanced materials. Magnetron sputtering underpins the manufacture of many products ranging from semiconductor microelectronics to energy efficient windows. This project will create a new generation sputtering process fully compatible with current technology but capable of synthesising new phases and new film microstructures with greatly enhanced performance.
Integrated data-tested theory and modelling of type three solar radio emissions. Type three solar radio emissions, the Sun's most powerful and common, are the archetypal collective radio phenomenon in space physics and astrophysics. The project will integrate new theoretical work and simulations into a first integrated data-tested theory that can explain type three bursts, resolve long standing issues, and constrain solar physics.
Prediction of solar activity and space weather by automated analyses of solar radio and magnetic field observations and simulations. This project will build world-recognised capabilities to forecast space weather events at Earth in time to take protective measures. It involves around the clock automated identification and analysis of specific solar radio bursts, forecasting solar activity that results in transients moving Earth-ward, and simulations to predict when these will reach Earth.