Signaling Pathways To Enhance Potency Of AMPK-targeting Drugs
Funder
National Health and Medical Research Council
Funding Amount
$661,966.00
Summary
Sedentary lifestyles and consumption of high energy foods has led to epidemics of obesity-related metabolic diseases that place enormous financial and medical burden on the Australian economy. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK) which functions as both a cellular fuel gauge and co-ordinator of whole-body metabolism. Our goal is to improve AMPK drug potency by identifying novel processes that sensitize AMPK to drugs.
A New Function For An Old Enzyme: Src Protein Kinase Directs Excitotoxic Neuronal Death In Stroke
Funder
National Health and Medical Research Council
Funding Amount
$513,975.00
Summary
In our previous investigation of how brain cells die in patients suffering from stroke, we found that stroke causes aberrant activation of an enzyme called Src in the affected brain cells. Furthermore, this aberrantly activated Src directs the brain cells to undergo cell death. Our proposal, which aims to decipher this neurotoxic mechanism of the aberrantly activated Src will benefit development of new therapeutic strategies to reduce brain damage in stroke patients.
The Molecular Mechanism Of Sphingosine Kinase Activation
Funder
National Health and Medical Research Council
Funding Amount
$442,500.00
Summary
Many cell processes like growth, death and differentiation are controlled by hormones and other molecules that interact with receptors on the outside of the cell. When this type of molecule binds to a receptor, it often triggers the production of signaling molecules inside the cell that initiate a change in the cells behaviour. The lipid molecule, sphingosine phosphate has been identified as such a signaling molecule that appears to be involved in the regulation of a diverse array of important m ....Many cell processes like growth, death and differentiation are controlled by hormones and other molecules that interact with receptors on the outside of the cell. When this type of molecule binds to a receptor, it often triggers the production of signaling molecules inside the cell that initiate a change in the cells behaviour. The lipid molecule, sphingosine phosphate has been identified as such a signaling molecule that appears to be involved in the regulation of a diverse array of important mammalian cellular processes. Recent studies have found that sphingosine phosphate is involved in the inflammation of cells, and if its production can be blocked, inflammation is not seen. Therefore, this provides a potential target for therapeutic intervention in the inflammation process. However, the manner by which cells regulate sphingosine phosphate levels is not well known. It is known that sphingosine phosphate is produced by the enzyme sphingosine kinase, and strong evidence suggests that changes in this enzyme's activity in the cell regulate sphingosine phosphate levels. However, how the cell changes the levels of sphingosine kinase activity is completely unknown. This study will investigate this problem with the view that understanding this process will allow the development of new drugs to block increases in sphingosine kinase activity, preventing increases in sphingosine phosphate levels, and it turn, preventing cellular inflammation.Read moreRead less
Regulation Of Ca2+/calmodulin Dependent Protein Kinase Kinase-2 By Phosphorylation
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
This project will study the regulation of an enzyme called CaMKK2, which plays a pivotal role in controlling a number of important biological functions including brain development, regulation of appetite, energy metabolism and blood pressure. Understanding how this enzyme is regulated may open new avenues for treating Type 2 diabetes, obesity, and cardiovascular disease.