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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100074
Funder
Australian Research Council
Funding Amount
$520,000.00
Summary
Facilities for automated high-throughput slide scanning and stereology. The equipment requested will facilitate the work of the Australian Mouse Brain Mapping Consortium, a consortium of Australian research groups collaborating to provide the only mouse model brain mapping capability in the country. The consortium brings together laboratory, neuroimaging and computational expertise in a comprehensive framework for imaging the mouse brain. This will help researchers to study mouse models of genet ....Facilities for automated high-throughput slide scanning and stereology. The equipment requested will facilitate the work of the Australian Mouse Brain Mapping Consortium, a consortium of Australian research groups collaborating to provide the only mouse model brain mapping capability in the country. The consortium brings together laboratory, neuroimaging and computational expertise in a comprehensive framework for imaging the mouse brain. This will help researchers to study mouse models of genetic and acquired disorders across the life-span. Remote viewing and analysis capabilities will help overcome the 'tyranny of distance', increasing national access to the facility. Repositories of digitised images will increase the availability of valuable research material to other Australian and international researchers.Read moreRead less
Rhombomeric Topography of Structures in the Adult Mouse: Evidence from Avian Homologies and Transgenic Mice. The brainstem of birds has been shown to be formed by a line of segments, like carriages of a train. The same arrangement exists in the embryos of mammals, but is hidden in the adult mammalian brain. We will transfer our detailed knowledge of bird brains to make a maps of the brainstem segments in adult mice. We will then test this map with special gene markers which will reveal the occul ....Rhombomeric Topography of Structures in the Adult Mouse: Evidence from Avian Homologies and Transgenic Mice. The brainstem of birds has been shown to be formed by a line of segments, like carriages of a train. The same arrangement exists in the embryos of mammals, but is hidden in the adult mammalian brain. We will transfer our detailed knowledge of bird brains to make a maps of the brainstem segments in adult mice. We will then test this map with special gene markers which will reveal the occult segmental pattern in adult mice. This work will give us a new way of understanding the organisation of brainstem centres that control breathing, cardiovascular functions and emotional states.Read moreRead less
Cellular and Neurochemical Basis of Drug Addiction. Addiction to the major drugs of abuse, including heroin, amphetamines, cocaine, nicotine and alcohol damage the lives and cause premature death of more than 20% of Australians. Addiction produces long-term disruption of brain processes that lead to loss of control over urges to consume drugs and persistent cycles of relapse to drug taking. This research will apply new neurochemical approaches to discover mechanisms of disrupted brain function t ....Cellular and Neurochemical Basis of Drug Addiction. Addiction to the major drugs of abuse, including heroin, amphetamines, cocaine, nicotine and alcohol damage the lives and cause premature death of more than 20% of Australians. Addiction produces long-term disruption of brain processes that lead to loss of control over urges to consume drugs and persistent cycles of relapse to drug taking. This research will apply new neurochemical approaches to discover mechanisms of disrupted brain function that occur during development of addiction and relapse that are critical for development of better strategies to treat the disorder. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453630
Funder
Australian Research Council
Funding Amount
$274,692.00
Summary
High-Speed Confocal Microscope Live Cell Recording System. The high-speed confocal microscope live cell recording system we are establishing represents new generation equipment. It allows quality imaging of selected subcellular regions of live cells combined with simultaneous electrophysiological recording at rates and sensitivity hitherto not possible. This equipment provides a window of opportunity for major research advances in that it allows real-time two and three-dimensional imaging of fun ....High-Speed Confocal Microscope Live Cell Recording System. The high-speed confocal microscope live cell recording system we are establishing represents new generation equipment. It allows quality imaging of selected subcellular regions of live cells combined with simultaneous electrophysiological recording at rates and sensitivity hitherto not possible. This equipment provides a window of opportunity for major research advances in that it allows real-time two and three-dimensional imaging of fundamental cellular activities that previously could not be viewed. It will allow major advances in priority health-related research and will provide an ideal research tool to introduce young scientists and students to cutting edge research.Read moreRead less
Effect Of Sex Steroids, Inflammation, Environmental And Biopsychosocial Factors On Cardiometabolic Disease Risk In Men
Funder
National Health and Medical Research Council
Funding Amount
$1,817,271.00
Summary
Heart disease is more frequent and occurs at an earlier age in men than women. The reason is unknown. Apart from obesity and associated disturbances of metabolism, changes in sex hormones such as testosterone, together with the effects of inflammation may be important, and may in turn be affected by environment, lifestyle behaviours, and stress. To untangle these relationships, we will use cutting edge technology, in a large sample of men, in partnership with other international scientists.