Receptor Signalling Through Intracellular Calcium Stores In Chromaffin Cells
Funder
National Health and Medical Research Council
Funding Amount
$461,000.00
Summary
The function of cells in the body is controlled by many hormones and neurotransmitters acting on the cell's surface. Hormones and transmitters mediate their effects by producing chemical signals within the cell that regulate its activities. One key cell signalling chemical is calcium, especially in nerve cells which have developed sophisticated mechanisms for using calcium to control their function. Recently, new levels of complexity have been discovered, both in how cell calcium levels are modi ....The function of cells in the body is controlled by many hormones and neurotransmitters acting on the cell's surface. Hormones and transmitters mediate their effects by producing chemical signals within the cell that regulate its activities. One key cell signalling chemical is calcium, especially in nerve cells which have developed sophisticated mechanisms for using calcium to control their function. Recently, new levels of complexity have been discovered, both in how cell calcium levels are modified by hormones and transmitters and in how these complex calcium signals are used by cells to control their function. This project will investigate how hormones and transmitters can produce different types of calcium signals in nerve cells, and how these signals affect different aspects of the nerve cell's function. In particular, it will establish how two different types of specialised calcium stores within nerve cells are used by different classes of hormone and transmitter, and the distinct cellular functions these two calcium stores can regulate. The results will provide fundamental new information on how nerve cells control their activity and may help identify potential new targets for drugs.Read moreRead less
The Role Of Glutamate Receptor Mediated Excititoxicity In Neurodegeneration And Huntington's Disease
Funder
National Health and Medical Research Council
Funding Amount
$467,310.00
Summary
Glutamate, the principal excitatory neurotransmitter in the brain, acts on three subtypes of ionotropic glutamate receptors (iGluRs), AMPA, kainate and NMDA receptors. Evidence suggests that aberrant NMDA receptor mediated calcium influx into neurons leads to excitotoxic cell death. Calcium influx through AMPA and kainate receptors has also been implicated in excitotoxic neurodegeneration. It is widely thought that excitotoxicity contributes to chronic neurodegenerative disease. We will test thi ....Glutamate, the principal excitatory neurotransmitter in the brain, acts on three subtypes of ionotropic glutamate receptors (iGluRs), AMPA, kainate and NMDA receptors. Evidence suggests that aberrant NMDA receptor mediated calcium influx into neurons leads to excitotoxic cell death. Calcium influx through AMPA and kainate receptors has also been implicated in excitotoxic neurodegeneration. It is widely thought that excitotoxicity contributes to chronic neurodegenerative disease. We will test this hypothesis by investigating degeneration in mutant mice with altered iGluR mediated calcium flux alone and combined with mutant genes known to cause Huntington s disease by: knocking-out the NMDA receptor in select brain regions of mice and determining if that protects against neurodegenerative pathology in those brain regions. generating mutant mice with kainate or AMPA-Rs that flux abnormally high amounts of calcium and determine if that predisposes the mouse brains to neurodegenerative pathology. These experiments will provide valuable animal models enabling a deeper understanding of neurodegenerative processes. The models will also provide invaluable resources for developing therapies to protect against neurodegeneration.Read moreRead less
Deciphering How PTEN Phosphatase Mediates Excitotoxic Neuronal Death
Funder
National Health and Medical Research Council
Funding Amount
$519,715.00
Summary
In stroke patients, oxygen deprivation indirectly induces massive nerve cell death by activating a cell death-promoting enzyme called PTEN. We aim at unravelling (i) how PTEN is activated by oxygen deprivation, (ii) where the activated PTEN is localised in cells, and (iii) how the activated and optimally localised PTEN induces nerve cell death. The study will benefit development of therapeutic strategies to protect against brain damage in stroke.