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
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
Promoting active travel and public transport for a post-pandemic world. In many major cities, COVID-19 stimulated the provision of open streets, pop up bike lanes and widened pedestrian access, prompting unprecedented increases cycling and walking. While this type of infrastructure has always been supported by urban planners and designers, the pandemic has served as a vital inflection point, enabling cities to pursue long-term sustainable transport initiatives, including investment in Active Tra ....Promoting active travel and public transport for a post-pandemic world. In many major cities, COVID-19 stimulated the provision of open streets, pop up bike lanes and widened pedestrian access, prompting unprecedented increases cycling and walking. While this type of infrastructure has always been supported by urban planners and designers, the pandemic has served as a vital inflection point, enabling cities to pursue long-term sustainable transport initiatives, including investment in Active Travel (AT). There is an opportunity to promote AT as part of an integrated transport strategy, and to develop tools for the robust evaluation of AT impacts to inform future investment strategies. This proposal will provide our partner organisation Transport for New South Wales (with the knowledge required to achieve this.
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The Treatment Of BOoking Gestational Diabetes Mellitus Study: The TOBOGM Study
Funder
National Health and Medical Research Council
Funding Amount
$2,197,280.00
Summary
Gestational diabetes mellitus (GDM) related pregnancy complications are reduced with treatment from 24-28 weeks pregnant. Many women are diagnosed/treated earlier without evidence of benefit and possible risk of harm. In TOBOGM women under 20 weeks pregnant with mildly raised blood glucose will be allocated by chance to either immediate treatment, or awaiting a repeat diabetes test at 24-28 weeks pregnant to decide treatment. Harmful and beneficial effects on mother and baby will be compared.
How Does Paternal Obesity Influence Offspring Glucose Tolerance?
Funder
National Health and Medical Research Council
Funding Amount
$503,398.00
Summary
Obesity and diabetes are closely related to these conditions in either parent, but how the father contributes is unclear. We have shown that normal females mated with obese fathers consuming high fat diet, produce offspring who develop glucose intolerance and impaired insulin secretion. This work will examine the mechanisms underlying this effect in the rat, testing a novel role for environmental factors in the father on disease in offspring that may be relevant to the growing obesity epidemic.
Integrating Attribute Decision Heuristics into Travel Choice Models that accommodate Risk Attitude and Perceptual Conditioning. This proposal has the specific objective of integrating two disconnected literatures that are having a major influence on the behavioural and statistical performance of discrete choice models in travel choice modelling. These fields are attribute processing strategies and the conditioning of the marginal utility of attributes by risk attitude and perceptual conditioning ....Integrating Attribute Decision Heuristics into Travel Choice Models that accommodate Risk Attitude and Perceptual Conditioning. This proposal has the specific objective of integrating two disconnected literatures that are having a major influence on the behavioural and statistical performance of discrete choice models in travel choice modelling. These fields are attribute processing strategies and the conditioning of the marginal utility of attributes by risk attitude and perceptual conditioning. These two major developments have not been jointly integrated into a behaviourally richer representation of choice making. Given the encouraging evidence from both literatures, the research will determine more precisely the benefits in terms of improved estimates of willingness to pay for specific attributes and also increased predictive power. 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
Shape adaptive structures with built-in compact smart material based actuators. Primary Australian aerospace manufacturers are sub-contractors and constantly compete in the global market. Their products are primarily control surfaces, e.g., Boeing 757 and 777 rudders, 737 Krueger flaps. In light of the development of the hingeless control surfaces (HCS) in the smart aircraft wing program in the USA, the economic benefits of this project are very high because (a) it will address the key technolo ....Shape adaptive structures with built-in compact smart material based actuators. Primary Australian aerospace manufacturers are sub-contractors and constantly compete in the global market. Their products are primarily control surfaces, e.g., Boeing 757 and 777 rudders, 737 Krueger flaps. In light of the development of the hingeless control surfaces (HCS) in the smart aircraft wing program in the USA, the economic benefits of this project are very high because (a) it will address the key technological issue identified in the HCS program; and (b) it will enhance Australian manufacturers¡¯ technological standing and input in the design and manufacturing of next generation HCS by providing highly trained people with world-leading niche technology.Read moreRead less
Active shape control of large thin-walled structures using ferroelectric single crystals. Ferroelectric single crystals were invented 5 years ago, and they possess many superior properties compared to conventional piezoelectric materials, particularly the induced strain up to 1.5%, an order higher than conventional materials. This project aims to poineer the application of these new and powerful smart materials as actuators and sensors to shape control of smart structures. The expected outcome ....Active shape control of large thin-walled structures using ferroelectric single crystals. Ferroelectric single crystals were invented 5 years ago, and they possess many superior properties compared to conventional piezoelectric materials, particularly the induced strain up to 1.5%, an order higher than conventional materials. This project aims to poineer the application of these new and powerful smart materials as actuators and sensors to shape control of smart structures. The expected outcomes are (a) a new constitutive theory for the non-linear behaviour of ferroelectric single crystals; (b) a novel definition and formulation for the shape control problem; and (c) an innovative theoretical framework for design optimization of shape control of smart structures using ferroelectric single crystals.Read moreRead less
Morphing flexible structures with lead lanthanum zirconium titanate (PLZT) based optical actuators. Lead lanthanum zirconate titanate (PLZT) materials yield mechanical strains when exposed to near ultraviolet light as a result of combined photovoltaic and converse piezoelectric effects. They offer actuation strain on par with piezoelectric materials and other advantages, such as wireless light-to-mechanical energy transfer, immunity from electrical and magnetic disturbances and fast response wi ....Morphing flexible structures with lead lanthanum zirconium titanate (PLZT) based optical actuators. Lead lanthanum zirconate titanate (PLZT) materials yield mechanical strains when exposed to near ultraviolet light as a result of combined photovoltaic and converse piezoelectric effects. They offer actuation strain on par with piezoelectric materials and other advantages, such as wireless light-to-mechanical energy transfer, immunity from electrical and magnetic disturbances and fast response with the transparent electrode design. This project aims to pioneer the application of PLZT optical actuators in morphing flexible structures leading to development of wireless smart structures technology and opt-electromechanical systems such as medical instruments.Read moreRead less