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Characterising An Important Control Point In Cholesterol Synthesis Beyond HMG-CoA Reductase
Funder
National Health and Medical Research Council
Funding Amount
$480,739.00
Summary
The statins are the ‘go-to’ drugs for treating heart disease; blocking a very early, highly-controlled step in the pathway producing cholesterol. However, they inhibit the production of other vital molecules which explains why some patients do not tolerate them. We have identified that a later enzyme in this pathway is also highly controlled and here aim to characterise the molecular mechanisms involved. This work could translate into the development of even safer drugs for treating cholesterol- ....The statins are the ‘go-to’ drugs for treating heart disease; blocking a very early, highly-controlled step in the pathway producing cholesterol. However, they inhibit the production of other vital molecules which explains why some patients do not tolerate them. We have identified that a later enzyme in this pathway is also highly controlled and here aim to characterise the molecular mechanisms involved. This work could translate into the development of even safer drugs for treating cholesterol-related diseases.Read moreRead less
Our goal is to discover new mechanisms involved in our cells’ delicate balancing act with respect to cholesterol levels. Understanding how production of cholesterol is controlled in our cells is key to developing new drugs aimed at preventing its excessive accumulation. This will have long-term benefits for health considering that a cellular imbalance in cholesterol is involved in two of the most common conditions threatening the health of Australians, namely heart disease and Alzheimer’s diseas ....Our goal is to discover new mechanisms involved in our cells’ delicate balancing act with respect to cholesterol levels. Understanding how production of cholesterol is controlled in our cells is key to developing new drugs aimed at preventing its excessive accumulation. This will have long-term benefits for health considering that a cellular imbalance in cholesterol is involved in two of the most common conditions threatening the health of Australians, namely heart disease and Alzheimer’s disease.Read moreRead less
Adiponectin And Cholesterol: A Driving Force In NASH Immunopathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$436,017.00
Summary
This project examined the role of dietary cholesterol in the pathogenesis of fatty liver disease in a rodent model. We have been able to demonstrate that diets high in cholesterol lead to the development of inflammatory foci in the liver, elevations in the amount of hepatic ceramides (a lipid byproduct) and then leads to the activation of inflammatory molecular pathwways that lead to liver fibrosis. The latter results in end stage liver disease, and in some to the development of liver cancer.
Lipid Trafficking At Membrane Contact Sites: The Role Of Oxysterol-Binding Protein-Related Protein 5 And 8 (ORP5 And ORP8)
Funder
National Health and Medical Research Council
Funding Amount
$466,400.00
Summary
Abnormal subcellular lipid distribution is associated with a number of common diseases including cancer, cardiovascular disease, and Alzheimer’s disease. The overall aim of this proposal is to identify and characterize new molecules that regulate the transport of lipids between different cell membranes. Results from the proposed studies will help developing novel therapeutic agents against common human diseases.
ABCA12 – A New Regulator Of Cellular Lipid Metabolism And Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$786,676.00
Summary
Dysregulation of cholesterol metabolism plays a key role in a number of diseases – from diabetes and atherosclerosis to neurological and skin disorders. Mechanisms of regulation of cholesterol metabolism are poorly understood. We have recently discovered a new pathway regulating cholesterol metabolism and in this study we will investigate molecular, cellular and physiological mechanisms of this pathway and will identify the possibilities to target it for therapeutic intervention.
The Role Of Adipose Tissue Cholesterol In Metabolic Diseases
Funder
National Health and Medical Research Council
Funding Amount
$888,340.00
Summary
Adipose tissue is important for human health. Adipose tissue can normally store a significant amount of cholesterol. Impairment of this function will cause a number of devastating diseases such as heart disease and stroke. The proposed work will help understand how adipose tissue store cholesterol. Results from this work may lead to novel therapeutic strategies against obesity and heart disease.
The Dengue Virus Glycoprotein NS1 Binds Cholesterol And Mediates Cellular Activation
Funder
National Health and Medical Research Council
Funding Amount
$632,029.00
Summary
Cholesterol has been shown to play a vital role in the life cycle of many viruses. This project will investigate the basis of dengue virus interaction with this important host molecule and along with investigations of how dengue is able to stimulate host cells, will provide new insights into the way these viruses cause severe disease. Findings from this study will also aid in the development of new drug strategies for dengue and related viruses such as West Nile virus.
Identification And Characterization Of Novel Proteins In Endosomal Cholesterol Transport
Funder
National Health and Medical Research Council
Funding Amount
$540,636.00
Summary
Abnormal subcellular distribution of cholesterol is associated with a number of common diseases including heart disease and Alzheimer’s disease. The overall aim of this proposal is to identify and characterize novel molecules that regulate the transport of intracellular cholesterol. Results from the proposed studies will provide important insights into the molecular mechanisms governing intracellular cholesterol transport and distribution, and will lead to better treatment strategies against hea ....Abnormal subcellular distribution of cholesterol is associated with a number of common diseases including heart disease and Alzheimer’s disease. The overall aim of this proposal is to identify and characterize novel molecules that regulate the transport of intracellular cholesterol. Results from the proposed studies will provide important insights into the molecular mechanisms governing intracellular cholesterol transport and distribution, and will lead to better treatment strategies against heart disease and dementia.Read moreRead less
We aim to develop a new class of cholesterol-lowering drugs by blocking the interaction between a protein in the blood called PCSK9 and its receptor, which is implicated in cholesterol absorption. We will do this by designing small stable peptides (mini proteins) that mimic part of the receptor and have the potential to interfere with the normal PCSK9 binding process. These drugs should be less expensive and potentially less immunogenic than competing therapies based on antibodies.
Microparticles In NASH: Origins, Pathogenic Roles, And Biomarker Of Disease Activity
Funder
National Health and Medical Research Council
Funding Amount
$540,633.00
Summary
30% of Australians have non-alcoholic fatty liver disease (NAFLD). Cirrhosis is the third cause of death; only 10-25% of NAFLD livers show steatohepatitis (NASH), which leads to cirrhosis. We have found that microparticles (MPs), small fragments of cell membranes, circulate in NASH but not in ordinary fatty liver. We will now explore ways in which MPs incite inflammation and liver fibrosis in NASH, and design new tests based on MPs to improve clinical assessment of patients with NAFLD/NASH.