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
What happens when viruses infect cells? How do they control the cells they infect? How do the make the cells do the things the virus wants? These are the questions that we aim to address within this research proposal. Primarily we hope to identify how viruses are able to replicate in cells and avoid immune detection. We believe these processes are related.
Understanding The Biosynthesis Of Complex Polyketide Lipid Toxins In Pathogenic Mycobacteria
Funder
National Health and Medical Research Council
Funding Amount
$298,898.00
Summary
Some major infectious diseases such as tuberculosis are caused by bacteria that make very unusual lipids (fats) that can kill human cells or interfere with the human immune system. The aim of this project is to work out how bacteria make these lipids. This knowledge will open up new avenues for treatments to stop bacterial lipid production and prevent disease. There are also potential applications in harnessing the bacterial lipid machinery to make new drugs and a wide range of other chemicals.
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.
Coenzyme A Synthesis In The Human Malaria Parasite, Plasmodium Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$428,250.00
Summary
Malaria is responsible for hundreds of millions of cases and an estimated 1.5-2.7 million deaths each year. The disease is caused by a microscopic parasite which is becoming increasingly resistant to antimalarial drugs. There is a very real possibility that there will soon be parts of the world in which malaria is an untreatable disease, and there is an urgent need to identify new drug targets. This work focuses on a particular biochemical pathway in the human malaria parasite, Plasmodium falcip ....Malaria is responsible for hundreds of millions of cases and an estimated 1.5-2.7 million deaths each year. The disease is caused by a microscopic parasite which is becoming increasingly resistant to antimalarial drugs. There is a very real possibility that there will soon be parts of the world in which malaria is an untreatable disease, and there is an urgent need to identify new drug targets. This work focuses on a particular biochemical pathway in the human malaria parasite, Plasmodium falciparum. The pathway mediates the conversion of the nutrient, vitamin B5, into a molecule called Coenzyme A. It plays an essential role in the intraerythrocytic parasite and our preliminary data indicate that components of this pathway hold significant potential as antimalarial drug targets. In this project we will use a range of biochemical and molecular biology approaches to characterise in detail the components of this pathway in the parasite and to explore the possibility that compounds that inhibit this pathway may be of value as much-needed new antimalarial agents.Read moreRead less
I have discovered particular factors produced by our white blood cells have the ability to shut down or boost protein production in the gut, pancreas and lung. My vision is to harness these to devise new strategies for treatments for infectious and non-infectious diseases (inflammatory bowel disease, diabetes) that have a high burden on our healthcare system.