Targeting TRPV4 Activation Mechanisms To Reveal Novel Pain Therapies
Funder
National Health and Medical Research Council
Funding Amount
$580,938.00
Summary
Pain nerves sense painful chemical and physical stimuli, by opening protein "ion channels" which let small electric currents traverse the cell membrane. This pain signal is transmitted to the spinal cord and then the brain, where it is perceived as pain and elicits a reaction. But we don't know how the ion channels open. This project will investigate how receptors for painful substances open ion channels to cause pain. Understanding this mechanism will help us to make new drugs to treat pain.
The Role Of Phosphorylation And Signalling For Invasion Of Plasmodium Falciparum Into Human Erythrocytes.
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
The intracellular signals that govern Plasmodium falciparum malaria invasion of the red blood cell are poorly understood. It is likely calcium dependent phosphorylation leads to recruitment and activation of a cascade of proteins. This study combines a break-through in purification of viable P. falciparum merozoites with proteomic analysis of phosphorylation states to assess intracellular signalling. It is expected the processes identified will be unique to P. falciparum and targetable by drugs.
Examining The Intracellular Pathways Regulated By GM-CSF In Macrophages And The Role In Diseases Such Arthritis.
Funder
National Health and Medical Research Council
Funding Amount
$63,567.00
Summary
A protein, termed GM-CSF, has been shown to be important in inflammatory conditions, like rheumatoid arthritis. GM-CSF can modify the properties of a key white blood cell, the macrophage, causing macrophages to produce factors harmful to host tissue. Various therapies are being developed to block GM-CSF, however discovering other drugs that block the intracellular actions of GM-CSF in macrophages are needed. Therefore the molecular pathways governing these actions need to be defined.
Legionella bacteria are the major cause of Legionnaire’s Disease, a common form of acute pneumonia. Here we will study how the bacteria avoid killing in human cells by establishing an intracellular niche that is sequestered from the normal host cell defence pathways. In particular we hope to understand how the bacteria regulate a major protein modification pathway called ubiquitination.
Role Of The Microglial Adaptor Molecule TYROBP In Alzheimer’s Disease Pathology
Funder
National Health and Medical Research Council
Funding Amount
$469,433.00
Summary
Immune activation characterizes Alzheimer’s disease (AD) brains; however, how it impacts AD progression is not understood. Our previous studies in AD brains identified the immune molecule TYROBP, pointing at both beneficial and detrimental effects triggered by this molecule. Here, we aim to understand in detail how TYROBP is involved in AD and how we can enhance its beneficial effects and decrease its unintended actions.
A Sweet Therapeutic For Vascular Disease In Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$685,453.00
Summary
This project will advance a new drug to treat pregnant women diagnosed with the disease preeclampsia, and prevent them and their baby from becoming seriously ill. It will investigate how a novel sugar compound acts directly on the mother's blood vessels to restore normal vascular function, and provide the necessary preclinical proof-of-concept data to proceed to clinical trials.