Regulation of ion transport in the respiratory epithelium in health and disease
The project will focus on elucidating the mechanisms by which respiratory pathogens including influenza, parainfluenza, avian influenza (H5N1) viruses, and microbacterium tuberculosis affect ion transport in the respiratory epithelium and on the development of new treatments for cystic fibrosis including the use of pharmacological agents and stem cell treatment.
The ion transport mechanisms in the lungs regulate the thickness of the layer of alveolar fluid bathing the lung surface. This fluid layer is important for mucociliary clearance, a mechanism that removes harmful airborne particles and microorganisms from the lung. Several respiratory pathogens are known to affect lung ion and fluid transport. Influenza A virus activates a cellular signaling pathway that inhibits sodium and water absorption in the lung and induces pulmonary oedema. A more severe effect is observed following H5N1 infection. How H5N1 does this is, however, unknown. In addition, ion transport disturbance is attributable to lung infection in cystic fibrosis lung disease where lung chloride secretion is decreased and Na+ and water absorption is increased. One way to treat this condition is to introduce new healthy cells to the lung or to correct ion transport activity in the lung using pharmacological agents. The aims of this project are:
- To identify the cellular mechanisms that underlie the pathophysiology of avian and human influenza and tuberculosis in order to provide the basic information required to understand and overcome the pathophysiological effects of other respiratory infections.
- To develop a new treatment using chord blood stem cells for correcting ion transport activity in cystic fibrosis lung.
- To develop new pharmacological agents that target electrolyte transport in the lung for treatment of cystic fibrosis.
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The opportunity ID for this research opportunity is: 171