Inosine-5' Monophosphate Dehydrogenase (IMPDH) is an enzyme responsible for providing a form of energy to cells, so that they may undertake their correct functions. Recently, we have demonstrated that IMPDH also has a role in the formation of fat droplets within cells, when they are exposed to excessive nutrients. In mammals, excess consumed energy is stored as fat droplets within all cells. In fat cells, the energy is stored in very large droplets, and we see this as extra body fat. This is som ....Inosine-5' Monophosphate Dehydrogenase (IMPDH) is an enzyme responsible for providing a form of energy to cells, so that they may undertake their correct functions. Recently, we have demonstrated that IMPDH also has a role in the formation of fat droplets within cells, when they are exposed to excessive nutrients. In mammals, excess consumed energy is stored as fat droplets within all cells. In fat cells, the energy is stored in very large droplets, and we see this as extra body fat. This is sometimes associated with an alteration in the hormone production of the cells, leading to problems such as diabetes. In other cells, the excess energy is stored as tiny fat droplets (lipid bodies) that can adversely affect the function of the cell. We have shown that blocking the action of IMPDH can interfere with the accumulation of fat in both fat cells and other types of cell. This suggests that IMPDH has an important role in the development of obesity and associated problems such as diabetes. In this study we aim to investigate in detail the role of IMPDH in the accumulation of fat droplets in cells. We will do this by looking at the effects of different forms of IMPDH in different cell types, including human fat cells. We will also study cells and animals with increased or decreased amounts of IMPDH, and investigate the effects of this on the development of increased fat stores and insulin resistance. These studies will increase our understanding of the role of IMPDH in the development of obesity, and may lead to identification of new avenues of treatment for obesity and type 2 diabetes.Read moreRead less
Development Of Recombinant RsolCD39-PSGL As A Novel Therapeutic With Anti-thrombotic And Anti-inflammatory Effects
Funder
National Health and Medical Research Council
Funding Amount
$186,367.00
Summary
Heart disease and stroke are due to a narrowing of arteries followed by occlusion, due a combination of clot formation initiated by platelet clumping, and inflammation surrounding the vessel wall. The currently available drugs are often limited by the adverse reaction of bleeding. We will investigate the efficiency of a new drug to prevent clot formation and inflammation.
The prevalence of heart disease and stroke is increasing in the affluent world. These disorders are due to a narrowing of arteries due to clot formation, thereby reducing available blood supply to the heart and brain. Blood vessel occlusion is due a combination of clot formation initiated by platelet clumping, and inflammation surrounding the vessel wall. Drugs that prevent the clumping of platelets on the inner lining of the blood vessels play an important role in the prevention and treatment o ....The prevalence of heart disease and stroke is increasing in the affluent world. These disorders are due to a narrowing of arteries due to clot formation, thereby reducing available blood supply to the heart and brain. Blood vessel occlusion is due a combination of clot formation initiated by platelet clumping, and inflammation surrounding the vessel wall. Drugs that prevent the clumping of platelets on the inner lining of the blood vessels play an important role in the prevention and treatment of heart attack and stroke. The currently available drugs are not universally effective and their use is often limited by adverse reactions. In this submission, we propose to investigate the efficiency of a new drug that will prevent clot formation and will also tackle inflammation. This drug is a derivative of an enzyme that is already present on platelets and cells that line blood vessels. We have modified this enzyme in a manner that will increase the enzyme activity on the surface of platelets and on the cells that line the blood vessel wall. We will thoroughly study this new drug by performing experiments in the laboratory as well as by studying its effect in mice.Read moreRead less
Fatty Acid Biosynthesis In The Malaria Chloroplast As A Drug Target
Funder
National Health and Medical Research Council
Funding Amount
$131,035.00
Summary
Malarial parasites contain a chloroplast similar to that of plants. We recently found genetic evidence suggesting the malaria chloroplast makes fats in the same way as plant chloroplasts. Additionally, we have found that drugs and herbicides that block plant chloroplast fat production stop growth of malaria cultures. Parasitologists had assumed that malaria was unable to make fats and would scavenge them from its human host so we have probably discovered a new metabolic pathway in these parasite ....Malarial parasites contain a chloroplast similar to that of plants. We recently found genetic evidence suggesting the malaria chloroplast makes fats in the same way as plant chloroplasts. Additionally, we have found that drugs and herbicides that block plant chloroplast fat production stop growth of malaria cultures. Parasitologists had assumed that malaria was unable to make fats and would scavenge them from its human host so we have probably discovered a new metabolic pathway in these parasites. We now propose to prove that the drugs work by blocking essential, chloroplast-based fat production in parasites. This could lead to novel treatment of malaria and related parasites.Read moreRead less
Bridging The Gap Between Cartilage Biology And Osteoarthritis Risk Prediction
Funder
National Health and Medical Research Council
Funding Amount
$512,256.00
Summary
Osteoarthritis is a painful and debilitating cartilage disease affecting just under 1 in 10 Australians and costs the Australian economy roughly $12 billion per year. This project will develop computational models of cartilage with the ability to incorporate genetic and environmental risk factors into a predictive model of cartilage disease.