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.
Targeting Phosphoinositide Metabolism In Leishmania
Funder
National Health and Medical Research Council
Funding Amount
$990,904.00
Summary
There is an urgent need to develop new drugs to treat human leishmaniasis, a disease that causes debilitating and life-threatening diseases in millions of people worldwide. This project will investigate whether it is possible to develop a new generation of drugs that target an important signaling pathway in these parasites that we have shown to be essential for virulence
A New Signaling Interface Shapes Cystic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$586,846.00
Summary
This grant investigates the previously uncharacterised association between the INPP5E and AURKA proteins. Both are involved in cell signaling and the development of cystic kidney disease. We will study the nature of this interaction and investigate whether it is possible to ameliorate kidney disease by inhibiting their actions in the developing and adult kidney.
Modulating Neuronal Secretion By The PI3-kinase Pathway
Funder
National Health and Medical Research Council
Funding Amount
$516,855.00
Summary
Neuronal communication relies on the process of exocytosis by which neurons release neurotransmitter. Exocytosis is critical for the simplest reflex movement to complex tasks such as learning and memory, and is altered in several neurodegenerative pathologies. We will investigate how certain lipids control exocytosis. This research is important for understanding how neurons communicate in health and disease and is relevant to other processes such as insulin release in diabetes.
The Neuronal PIKfyve Complex Regulates Neurotransmission And Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$372,965.00
Summary
Neuronal communication is essential for the functioning of our bodies and mind. We have identified a novel pathway for the regulation of this process involving a little studied lipid, PI3,5P2. This lipid also appears to be important for neuronal survival. We will investigate the regulation and function of this lipid in neurons. The outcomes of this proposal will be an important step closer to understanding the processes underlying neuronal communication and neurodegeneration.
Following a meal glucose circulates in the blood and is taken up into cells via movement of an intracellular glucose transporter from the inside of the cell to fuse with the cell membrane and subsequent transfer of the glucose into the cell. This process is triggered by insulin. One of the commonest diseases resulting from a failure of this cellular process is diabetes. A common form of diabetes which occurs in many adults in Australia results from insulin resistance, whereby the effects of insu ....Following a meal glucose circulates in the blood and is taken up into cells via movement of an intracellular glucose transporter from the inside of the cell to fuse with the cell membrane and subsequent transfer of the glucose into the cell. This process is triggered by insulin. One of the commonest diseases resulting from a failure of this cellular process is diabetes. A common form of diabetes which occurs in many adults in Australia results from insulin resistance, whereby the effects of insulin are diminished and cells become increasingly unable to uptake glucose. Recent studies have demonstrated that a novel enzyme known as SHIP-2 may play a role in regulating insulin action in cells. Deletion of SHIP-2 in mice results in these animals have increased sensitivity to insulin, low blood glucose levels, and a greatly enhanced ability to take up glucose in cells in response to low dose insulin. Our laboratory has been working on the cellular mechanisms regulating SHIP-2 function. We have recently revealed the intracellular location of SHIP-2 and also demonstrated how SHIP-2 is localized in the cell. These studies have shown that SHIP-2, via interactions with other proteins, regulates the actin cytoskeleton immediately beneath the cell membrane and this may be a mechanism for facilitating cellular glucose uptake. This research proposal aims to determine how SHIP-2 facilitates glucose uptake into cells. We will make cell lines and transgenic animals which express high levels of this enzyme and determine the functional consequences on insulin stimulated glucose uptake. Collectively these studies in the long term may facilitate better treatment strategies for diabetic patients.Read moreRead less