Do Synaptic-like Mechanisms Control Insulin Secretion?
Funder
National Health and Medical Research Council
Funding Amount
$593,235.00
Summary
An estimated 415 million people world-wide were diagnosed with diabetes in 2015. One of the causal factors in disease is the dysregulation of insulin secretion. We have developed new techniques to study insulin secretion that has led us to propose a new model for secretory control. This proposal sets out experiments to critically test this model. The outcomes could have wide-reaching impact on understanding and for future treatment and prevention of the diabetes.
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.
The Structure And Function Of The Apical Domain In Insulin Secreting Beta Cells.
Funder
National Health and Medical Research Council
Funding Amount
$571,741.00
Summary
Loss of control of insulin secretion is causal in diabetes and therefore its understanding is a key goal to shed light on the disease. We have recently identified a new domain in the insulin secreting cells, called the apical domain. This proposal will define the role of this apical domain in controlling insulin secretion. The outcomes could provide new insights into how diabetes develops and new targets for therapies.
The Preferential Release Of Young Insulin Secretory Granules.
Funder
National Health and Medical Research Council
Funding Amount
$670,005.00
Summary
The aim of this study is to investigate the cause of reduced glucose induced insulin secretion in type 2 diabetes. In pancreatic beta-cells, insulin is packaged and stored in secretory granules (SGs). Upon stimulation, these SGs deliver insulin to the bloodstream. It is known that insulin SGs exist in two functionally distinct pools; and one pool is preferentially secreted upon stimulation. How a cell can differentiate the two SG pools is unclear, and we will address this issue in this project.
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
Regulation Of Secretion Of The Fungal Virulence Determinant, Phospholipase B
Funder
National Health and Medical Research Council
Funding Amount
$487,500.00
Summary
Serious systemic infections due to fungi have increased dramatically in the past few years, especially in people with poorly functioning immune systems. Treatment of these conditions is problematic because the few drugs which are available are not highly effective, and-or cause significant side-effects. Little is understood of how fungi cause disease, and this problem must be addressed if these infections are to be contained. We have discovered that the enzyme, phospholipase B (PLB), is secreted ....Serious systemic infections due to fungi have increased dramatically in the past few years, especially in people with poorly functioning immune systems. Treatment of these conditions is problematic because the few drugs which are available are not highly effective, and-or cause significant side-effects. Little is understood of how fungi cause disease, and this problem must be addressed if these infections are to be contained. We have discovered that the enzyme, phospholipase B (PLB), is secreted by the disease-causing fungus, Cryptococcus neoformans, and that it is important in enabling the fungus to invade the host's cells and spread around the body from the lungs to the brain, where it can cause meningoencephalitis. PLB is also produced by other disease-causing fungi. The mechanism of PLB secretion is completely unknown. In this project we aim to determine the pathways involved in PLB secretion with the intention of exploiting steps unique to pathogenic fungi, for the future design of new anti-fungal drugs.Read moreRead less
Preventing railway suicide: An open-systems perspective. Preventing railway suicide: An open-systems perspective. This project aims to develop an automated suicide risk detection system to reduce the incidence and impact of railway suicide, which has a devastating effect on victims’ families, station staff, train drivers, emergency workers, and bystanders. This project will use open-systems theory to develop two complementary information systems for more effective detection and reporting of suic ....Preventing railway suicide: An open-systems perspective. Preventing railway suicide: An open-systems perspective. This project aims to develop an automated suicide risk detection system to reduce the incidence and impact of railway suicide, which has a devastating effect on victims’ families, station staff, train drivers, emergency workers, and bystanders. This project will use open-systems theory to develop two complementary information systems for more effective detection and reporting of suicide risk; use these systems to investigate how different situational factors interact with different combinations of service interventions to influence suicide risk; and share the findings to reduce railway suicide in Australia and overseas.Read moreRead less
Service Ecosystems Management for Collaborative Process Improvement. Australian government agencies currently explore opportunities for streamlining their business processes. A promising approach relates to the improvement of cross-agency processes based on service-enabled technologies. This project will use requirements within Queensland Government for the design of a service ecosystem and methodological and management concepts to derive a general framework for intra-organisational ecosystems. ....Service Ecosystems Management for Collaborative Process Improvement. Australian government agencies currently explore opportunities for streamlining their business processes. A promising approach relates to the improvement of cross-agency processes based on service-enabled technologies. This project will use requirements within Queensland Government for the design of a service ecosystem and methodological and management concepts to derive a general framework for intra-organisational ecosystems. Though the focus will be on government processes, the project will generalise beyond this scope for a wider uptake of service ecosystems in Australian organisations. This will lead to reduced process costs and risks and will leverage the exploration of new revenue streams, e.g. shared services and reward schemes.Read moreRead less
Intelligent Design Advisor for Manufacturing Process Knowledge within Concurrent Engineering in the Aerospace Industry. At present the design of engineering components in the aerospace industry is accomplished by experts from design and manufacturing either sequentially or in collaboration. If performed in sequence then time and quality is jeopardised. If performed in collaboration then more manpower than is necessary is expended. The aim of this project is to develop an intelligent design advis ....Intelligent Design Advisor for Manufacturing Process Knowledge within Concurrent Engineering in the Aerospace Industry. At present the design of engineering components in the aerospace industry is accomplished by experts from design and manufacturing either sequentially or in collaboration. If performed in sequence then time and quality is jeopardised. If performed in collaboration then more manpower than is necessary is expended. The aim of this project is to develop an intelligent design advisor for Manufacturing Process Knowledge that will provide this expert knowledge to the design engineer in order to speed up the design process while reducing costs and still maintaining the high standard of quality necessary in the Aerospace industry.Read moreRead less
Internet Timing for the Ages: Establishing the New Timekeeping System. All computers incorporate a software clock, essential to myriad software applications. An economic way to synchronize such clocks is over a network, however the approach the Internet currently depends upon is unreliable and vulnerable. This project aims to establish a new architecture for networked timekeeping, built on future-proofed fundamentals, that will for the first time address each of accuracy, reliability, and trust. ....Internet Timing for the Ages: Establishing the New Timekeeping System. All computers incorporate a software clock, essential to myriad software applications. An economic way to synchronize such clocks is over a network, however the approach the Internet currently depends upon is unreliable and vulnerable. This project aims to establish a new architecture for networked timekeeping, built on future-proofed fundamentals, that will for the first time address each of accuracy, reliability, and trust. The expected outcome is a national prototype, serving the public with accurate and trusted time, that will form the basis of the next generation timekeeping system for the Internet and the Internet of Things. Expected benefits include enhanced productivity across the digital economy, and resilience to GPS failures.Read moreRead less