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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
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.
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
Correlative Structure-function Studies Of Cis- And Trans-Golgi Membrane Traffic In Mammalian Cells
Funder
National Health and Medical Research Council
Funding Amount
$649,531.00
Summary
This project combines imaging by light and electron microscopy with additional techniques for studying protein function at the molecular level, to elucidate how changes in the 3D organisation of cellular machinery can lead to fundamental changes in the function and health of mammalian cells. Although this work includes detailed investigation of the 'insulin factory', it has the potential to modify established concepts on membrane traffic and protein secretion well beyond the field of diabetes.
Regulation Of Glucose Uptake By Tropomyosins And Myosins
Funder
National Health and Medical Research Council
Funding Amount
$609,320.00
Summary
Defective import of glucose from the blood into fat and muscle is a key cause of adult-onset diabetes. We have identified a novel mechanical structure within muscle and fat cells defined by the protein tropomyosin that is involved in glucose import and potentially provides new targets for treatment of adult-onset diabetes and obesity.
Studies Of A Novel Manganese Transporter In Lysosomes And Its Implications In Niemann-Pick Type-C Disease
Funder
National Health and Medical Research Council
Funding Amount
$527,036.00
Summary
Niemann-Pick type-C disease is a devastating disease affecting child central nervous system. It is due to too much build up of cholesterol in the lysosomal compartment of cells. Recent studies indicate that bivalent cations are involved in the development of the disease. We recently discovered a manganese transporter in the lysosomal compartment and its interaction of the a protein that causing the disease. We will elucidate how manganese transporter controls trace metal balance and may prevent ....Niemann-Pick type-C disease is a devastating disease affecting child central nervous system. It is due to too much build up of cholesterol in the lysosomal compartment of cells. Recent studies indicate that bivalent cations are involved in the development of the disease. We recently discovered a manganese transporter in the lysosomal compartment and its interaction of the a protein that causing the disease. We will elucidate how manganese transporter controls trace metal balance and may prevent the disease.Read moreRead less
Akt Kinase Signalling, Regulated Vesicular Transport And Lipid Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$337,850.00
Summary
How do metabolic cues tell cancer cells to make more membranes, or fat cells to make more fat? These are some of the questions that underpin this project, which explores the link between cell signalling, protein trafficking and fat metabolism. Specifically, we aim to define the role of an important signalling molecule (Akt) in intracellular transport and activation of a key integrator of fat metabolism (SREBP). This work will have wide-ranging implications for human health and disease.
Assembly And Misassembly Of Mitochondrial Respiratory Chain Complex I
Funder
National Health and Medical Research Council
Funding Amount
$520,520.00
Summary
Mitochondria are the powerhouses in our cells. They burn the carbon fuels we eat and store the energy by making ATP that is used for functions such as muscle contraction and triggering of nerves. Mitochondrial Complex I is a molecular motor that helps to make ATP. “Mitochondrial disease” is often seen when Complex I is not built properly and this results in early childhood death. In this project we will study how Complex I is built and how the mitochondria responds to assembly problems.
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
Intracellular Trafficking Of Copper And Platinum-based Chemotherapuetics
Funder
National Health and Medical Research Council
Funding Amount
$268,328.00
Summary
Platinum-based anti cancer drugs such as Cisplatin are effective against a number of cancers of the head, colon, lungs and ovaries. Tumour resistance to these drugs has been closely associated with changes in genes that control the movement of copper in and out of cells. We hypothesize that the same genes regulate distribution of both copper and Cisplatin. By investigating these pathways, we aim to find ways to predict and prevent tumour resistance to this important anti cancer treatment.