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
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
Transport, Assembly And Egress Of Herpes Simplex Virus In Neurones
Funder
National Health and Medical Research Council
Funding Amount
$639,661.00
Summary
Herpes simplex viruses 1 and 2 are important pathogens, causing encephalitis, blindness and severe neonatal infection but they also enhance the acquisition of HIV three-fold. The transport of the virus to and from the periphery to the spinal cord is a key component of their life cycle. Determination of the exact mechanism will assist in a general understanding of nerve function and the development of new strategies for antiviral drugs.
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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Signalling Pathways And Fungal Virulence – The Inositol Polyphosphate Kinase Pathway In Cryptococcus Neoformans
Funder
National Health and Medical Research Council
Funding Amount
$545,189.00
Summary
Bloodstream fungal infections kill millions of people per year world-wide and are costly to treat. A potentially fruitful strategy for developing new, urgently-needed drugs to fight these infections, is to target signalling pathways, which in fungi, are essential for establishing infection. This proposal investigates how one such pathway, the inositolpolyphosphate kinase pathway, allows fungi to establish infection and will determine which components are suitable targets for drug development.
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