EPITHELIAL ION TRANSPORT DEFECTS IN CYSTIC FIBROSIS: PATHOPHYSIOLOGY AND TREATMENT
Funder
National Health and Medical Research Council
Funding Amount
$290,440.00
Summary
The thin layer of fluid covering the surface of the air passages acts to protect the airway surface from drying. This fluid also allows the hair-like projections, or cilia, on the top of the airway cells to beat more effectively. The volume and composition of this fluid is determined by the movement of salt and water across the mucous membranes of the air passages. The importance of this fluid is shown by the problems that occur in Cystic Fibrosis (CF), the most common lethal inherited disease a ....The thin layer of fluid covering the surface of the air passages acts to protect the airway surface from drying. This fluid also allows the hair-like projections, or cilia, on the top of the airway cells to beat more effectively. The volume and composition of this fluid is determined by the movement of salt and water across the mucous membranes of the air passages. The importance of this fluid is shown by the problems that occur in Cystic Fibrosis (CF), the most common lethal inherited disease affecting Australians. In CF, altered salt transport causes drying of the airway surface which impairs the working of the cilia. This leads to retention of mucous in the airway with repeated bacterial infections damaging the lungs. Simple tests have been designed to directly measure the movement of salt across the surface of the nasal passage using a fine soft rubber tube. Movement of mucous in the nose is measured using other simple techniques that are currently used diagnostically. Together, these tests in the nose provide vital information about how the surface of normal human airway moves salt, water and mucous. Any differences found in CF patients will then give us a good idea of the problems found in the CF lung. We will study the interactions between calcium, sodium and chloride in the fluid lining the airways, measuring changes in salt and mucous movement. A range of testing procedures will be used in human volunteers, anaesthetised mice and isolated tissues from sheep. We have already demonstrated important links between the fluid lining the airways and salt movement, and we expect that this may lead to the development of new treatments for Cystic Fibrosis. This therapy will focus on treating the lung problems of CF patients, the major cause of disability. We anticipate that this preventative therapy may offer real benefits in the fight to cure CF.Read moreRead less
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.