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Molecular Characteristation Of The Adiponectin Receptors, AdipoR1 And AdipoR2: Identifying Strategies To Enhance Adiponectin Sensitivity And Reduce Cardiometabolic Disease.
Funder
National Health and Medical Research Council
Funding Amount
$334,634.00
Summary
Obesity and Type 2 diabetes (T2D) increase risk of cardiovascular disease (CVD), a leading cause of death in Australia. New drugs are required to reduce the health risks and financial burden of these diseases. Targeting hormone receptors to reduce fat storage in liver and skeletal muscle in obesity may improve insulin sensitivity and reduce blood sugar levels and therefore reduce CVD risk. This research will study how these receptors function in order to develop new drugs to reduce CVD risk.
PCSK9 is an inhibitor of the receptor that is responsible for removing LDL (the bad cholesterol) from the circulation. We will study the molecular mechanisms that inhibit PCSK9 at the protein level. This study is needed to understand if drugs that inhibit PCSK9 will diminish the risk of developing heart disease in patients who do not respond well to existing treatments, for example those who already had a cardiovascular event or those with familial hypercholesterolemia.
The Role Of The Glutamine Transporter SNAT3 In Ion Transport, Cell Signaling And Ammonia Detoxification
Funder
National Health and Medical Research Council
Funding Amount
$393,249.00
Summary
Hepatic encephalopathy is a syndrome observed in patients with liver cirrhosis and is caused by increased amounts of ammonia in the blood. The proposed project investigates a transporter that is involved in ammonia and glutamine metabolism in liver and brain. The two organs are critical to the pathology of liver failure and ammonia toxicity resulting from reduced liver function. The transporter thus could become a drug target for a variety of liver diseases.
Atherosclerosis is the disease which narrows arteries and causes heart attacks and stroke. It is one of the major causes of death in Australia. Although certain treatments, such as lowering blood cholesterol levels, reduce the incidence of atherosclerosis, current motality rates from this disease indicate that there is still a great need to improve our understanding and treament of the condition. In the development of atherosclerosis, some of the cells in the vessel wall accumulate large deposit ....Atherosclerosis is the disease which narrows arteries and causes heart attacks and stroke. It is one of the major causes of death in Australia. Although certain treatments, such as lowering blood cholesterol levels, reduce the incidence of atherosclerosis, current motality rates from this disease indicate that there is still a great need to improve our understanding and treament of the condition. In the development of atherosclerosis, some of the cells in the vessel wall accumulate large deposits of cholesterol. These cells are macrophages, derived from circulating white blood cells that have migrated into the vessel wall. Normally these cells are able to efficiently export excess cholesterol, but this process seems to fail in atherosclerosis. This project will study the molecular mechanism for cholesterol export from macrophages, concentrating on a the mechnisms by which recently identified cholesterol pumps operate. These are located in cell membranes, including at the cell surface, which is the site at which cholesterol is transferred to acceptors such as HDL and apoAI. By understanding how these pumps work, and how their activities are controlled, we will be better able to devise ways to increase their efficiency in atherosclerosis, and so to prevent the tissue cholesterol accumulation that drives this disease.Read moreRead less
Characterisation Of The Adiponectin Receptors - AdipoR1 And AdipoR2
Funder
National Health and Medical Research Council
Funding Amount
$445,158.00
Summary
The increasing incidence of cardiometabolic disease highlights an unmet need for novel therapeutic approaches. Greater understanding of the detail governing cardiometabolic function is required to provide a foundation to construct effective strategies. We will characterise 2 novel receptors that are important in the regulation and maintenance of cardiometabolic systems, seeking to identify strategies to enhance receptor, improve cardiometabolic function and reduce disease burden.
A unified model of amino acid homeostasis. This project aims to develop a unified model of amino acid homeostasis in mammalian cells and apply it to brain cells. The model will be underpinned by a mathematical algorithm that allows predicting amino acid levels in the cytosol based on fundamental parameters such as transport and metabolism. This project should provide the significant benefit of enabling the prediction of essential functions such as cell growth and survival.
The function of the ribbon structure of the Golgi apparatus in vertebrates. The aim of the project is to determine the function of the Golgi ribbon structure in higher order cell functions, including metabolism, cell cycle, and cell polarity in both cultured cells and whole organisms. Understanding of the functions of the Golgi has been restricted to the regulation of glycosylation and membrane transport. However, it is now recognised that the Golgi apparatus feeds into the wiring of a range of ....The function of the ribbon structure of the Golgi apparatus in vertebrates. The aim of the project is to determine the function of the Golgi ribbon structure in higher order cell functions, including metabolism, cell cycle, and cell polarity in both cultured cells and whole organisms. Understanding of the functions of the Golgi has been restricted to the regulation of glycosylation and membrane transport. However, it is now recognised that the Golgi apparatus feeds into the wiring of a range of cellular networks in higher organisms such as cell polarisation, directed migration, metabolism and autophagy. Vertebrates have evolved mechanisms for joining individual Golgi stacks into a ribbon structure. The relevance of this ribbon structure remains a mystery. The project aims to answer this major question in cell biology.Read moreRead less
Regulating nutrient uptake in intracellular parasites. Parasites impose a major economic and medical burden on human societies. In order to grow and reproduce, parasites scavenge nutrients from their animal or human hosts. As they move within and between hosts they encounter different levels of nutrients; how they adapt to these differences is poorly understood. This project aims to investigate the mechanisms by which the model parasite Toxoplasma senses and responds to the nutrients in its envi ....Regulating nutrient uptake in intracellular parasites. Parasites impose a major economic and medical burden on human societies. In order to grow and reproduce, parasites scavenge nutrients from their animal or human hosts. As they move within and between hosts they encounter different levels of nutrients; how they adapt to these differences is poorly understood. This project aims to investigate the mechanisms by which the model parasite Toxoplasma senses and responds to the nutrients in its environment, thereby shedding light on how they adapt to the different environments that they inhabit and, in the longer term, informing novel treatment strategies that aim to limit the parasites’ nutrient supply.Read moreRead less
The selective elimination of mitochondria from yeast cells: regulation and molecular mechanism . For healthy cells the quality of the mitochondrion, the cellular power plant, must be maintained. The results of this research will contribute to an understanding of the molecular mechanism for the removal of mitochondria from the cell, and ultimately inspire strategies for the treatment of diseases that result from faulty mitochondria.