Role Of Extracellular Surface Residues In Agonist Activation Of The Alpha1 Adrenoceptor
Funder
National Health and Medical Research Council
Funding Amount
$414,786.00
Summary
Most modern drugs act on a class of cellular proteins known as GPCRs. Despite their importance, little is known about how agonists acting from the outside of cells produce a change in GPCR structure allowing signalling to the cell's interior. We have identified new residues on the extracellular surface of the alpha1 adrenoceptor that dramatically affect agonist responses, opening the door to understanding the molecular process of GPCR activation and the development of drugs that can target diffe ....Most modern drugs act on a class of cellular proteins known as GPCRs. Despite their importance, little is known about how agonists acting from the outside of cells produce a change in GPCR structure allowing signalling to the cell's interior. We have identified new residues on the extracellular surface of the alpha1 adrenoceptor that dramatically affect agonist responses, opening the door to understanding the molecular process of GPCR activation and the development of drugs that can target different GPCR conformations.Read moreRead less
Does A Novel Estrogen Receptor Worsen Stroke Outcome?
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
This project will test whether a target protein for estrogen, called GPER, which is found in high levels in the brain, worsens stroke outcome. We will identify the key signalling pathways related to GPER in the brain after stroke and we hope to identify a new type of drug that could be used to treat stroke patients. It is possible that our work could at least partly explain why hormone replacement therapy can increase the risk of worsened outcome after stroke in women.
The Mechanisms Responsible For Tolerance At The Mu-opioid Receptor
Funder
National Health and Medical Research Council
Funding Amount
$562,815.00
Summary
Strong pain relieving opioid drugs like morphine lose their effectiveness when used for long periods because the single protein target for them in the body loses its� normal signalling functions. This research will determine the mechanisms responsible for this loss of function in brain nerve cells using novel methods to identify the molecular adaptations involved. This will provide a rational framework for development of pain relieving opioid drugs that can maintain long term efficacy.