Biology Of The Novel C-type Lectin Receptor DCL-1 In Innate And Adaptive Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$439,500.00
Summary
The innate immune system is the first line of defense in protecting the body from infection. Phagocytic (meaning eating) white blood cells, which include dendritic cells and macrophages are equipped with cell surface proteins These bind the many types of microbes that cause infection, allowing the phagocytes to destroy them (innate immune response). Furthermore, dendritic cells and macrophages have mechanisms to activate additional specific responses (adaptive immune response) mediated by lympho ....The innate immune system is the first line of defense in protecting the body from infection. Phagocytic (meaning eating) white blood cells, which include dendritic cells and macrophages are equipped with cell surface proteins These bind the many types of microbes that cause infection, allowing the phagocytes to destroy them (innate immune response). Furthermore, dendritic cells and macrophages have mechanisms to activate additional specific responses (adaptive immune response) mediated by lymphocytes (T and B cells). We have discovered a cell surface protein, termed DCL-1, which may play a role in uptake of microbes by phagocytes and activation of innate and adaptive immune responses. This project will examine the mechanisms whereby DCL-1 mediates these immune responses. Understanding the mechanism may allow us to exploit DCL-1 for tumor immunotherapy.Read moreRead less
A Single Fibre Study Of The Relationship Between Glucose Transport And Skeletal Muscle Contractility
Funder
National Health and Medical Research Council
Funding Amount
$284,625.00
Summary
Type 2 diabetes (a progressive disorder often accompanied by obesity) is claimed to be the most common metabolic disease in the world and is predicted to affect 1.15 million Australians by the year 2010. Muscle contraction (in the form of physical exercise or exercise training) is now an essential component in the management of type 2 diabetes and-or obesity.This project has been planned from a perspective that combines theoretical and experimental expertise in the field of muscle cell contracti ....Type 2 diabetes (a progressive disorder often accompanied by obesity) is claimed to be the most common metabolic disease in the world and is predicted to affect 1.15 million Australians by the year 2010. Muscle contraction (in the form of physical exercise or exercise training) is now an essential component in the management of type 2 diabetes and-or obesity.This project has been planned from a perspective that combines theoretical and experimental expertise in the field of muscle cell contractility with a keen interest in the role of skeletal muscle in glucose homeostasis. Work carried out within the scope of this project will contribute new insights into the pathogenesis of type 2 diabetes-obesity and new information on the cellular mechanisms involved in contraction-stimulated glucose transport by skeletal muscle. As part of this project we will develop single muscle cell-fibre preparations and appropriate protocols for monitoring cellular aspects of glucose transport in skeletal muscle. These preparations-protocols will have the potential to be used for testing anti-diabetic drugs directed towards intracellular targets. From an educational benefit point of view, the project will create the opportunity for 4-6 honours and 2-3 PhD students to acquire a rare and useful combination of skills and expertise in muscle cell biochemistry and physiology, while working on an issue of medical concern.Read moreRead less
Elucidating The Molecular Regulation Of Gp130 Complex Signalling In Lipid And Glucose Metabolism.
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
Overnutrition promotes obesity, which greatly increases the risk of type 2 diabetes and cardiovascular disease. We have provided evidence that activation of gp130 signalling may enhance insulin action and fatty acid oxidation in metabolically active tissues. My research proposal aims to elucidate the molecular regulation of gp130 complex signalling in lipid and glucose metabolism in important metabolic tissues.
Therapeutic Strategies And Screening Methods For PKC Epsilon Antagonists In The Treatment Of Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$157,375.00
Summary
Type 2 diabetes is a chronic disease affecting over a million Australians and hundreds of millions of people worldwide. Its prevalence is rising due to several factors such as an increase in caloric intake, the aging of the population, and the common sedentary lifestyle of Western civilization. Type 2 diabetes occurs when the pancreas is unable to produce enough insulin for the body to cope with rising blood glucose levels after a meal, and has been strongly linked to obesity. We have now shown ....Type 2 diabetes is a chronic disease affecting over a million Australians and hundreds of millions of people worldwide. Its prevalence is rising due to several factors such as an increase in caloric intake, the aging of the population, and the common sedentary lifestyle of Western civilization. Type 2 diabetes occurs when the pancreas is unable to produce enough insulin for the body to cope with rising blood glucose levels after a meal, and has been strongly linked to obesity. We have now shown that an enzyme found in the pancreas becomes inappropriately activated under conditions of fat oversupply, and plays an important role in the development of defects in insulin release from the pancreas in response to glucose. Excitingly, we have also shown that inhibition of this enzyme can partly reverse these defects once they have been established. We now intend to further validate this enzyme as a drug target by determining the optimum dosing regimen for the treatment of type 2 diabetes in a mouse model, and testing whether this approach can be used in conjunction with previously-developed drugs which promote insulin action, to improve bood glucose handling better than either treatment alone. This would promote the enzyme as a therapeutic strategy in the treatment of Type 2 diabetes. We also plan to develop a high throuhput screen to identify novel inhibitors of the enzyme, which will further increase the attractiveness of the project to pharmaceutical companies, who are better able to implent full commercialization of our findings.Read moreRead less