Altering Macrophage Phenotype For The Treatment Of Chronic Airway Disease And Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$904,556.00
Summary
The aim of this proposal is to identify mechanisms through which the Src family kinase Hck promotes innate immune cell-dependent, chronic lung inflammation and lung cancer development. Our preliminary data suggest that excessive Hck activity provides a molecular mechanism to skew macrophage polarization towards an alternatively activated, M2-like phenotype associated with chronic airways disease, and the tumour promoting microenvironment.
Regulation Of Epithelial Sodium Channels By Caveolin
Funder
National Health and Medical Research Council
Funding Amount
$408,391.00
Summary
Abnormal sodium absorption in the kidney, gut and lung is implicated in hypertension, cystic fibrosis and pulmonary oedema. Epithelial Na+ channels are a key component of the mechanism by which these organs absorb sodium. The project will investigate the mechanisms by which the activity of these channels is controlled and is intended to discover new approaches to treating abnormal sodium absorption.
Regulation Of The Sarcolemmal Na-K Pump By FXYD Proteins
Funder
National Health and Medical Research Council
Funding Amount
$268,264.00
Summary
Background. Pump molecules embedded in the membranes of all cells maintain a difference in composition between the cell content and the surrounding tissue fluids. Of these, the membrane sodium-potassium pump (Na+-K+ pump) is the most important. It uses metabolic energy generated in the cell to transport 3Na+ out in exchange for 2K+ transported in, and maintains a low concentration of Na+ and a high concentration of K+ within cells. The opposite applies to the surrounding tissue fluids. The conce ....Background. Pump molecules embedded in the membranes of all cells maintain a difference in composition between the cell content and the surrounding tissue fluids. Of these, the membrane sodium-potassium pump (Na+-K+ pump) is the most important. It uses metabolic energy generated in the cell to transport 3Na+ out in exchange for 2K+ transported in, and maintains a low concentration of Na+ and a high concentration of K+ within cells. The opposite applies to the surrounding tissue fluids. The concentration gradient for Na+ serves in mechanisms that couple transport of other ions and molecules to the downhill movement of Na+ in the direction determined by its concentration gradient. The transport of ions and molecules directly and indirectly due to the operation of the membrane Na+-K+ pump is very important for the function of all cells. Objectives. It is poorly understood how cells regulate the activity of their membrane Na+-K+ pumps. We will examine if small molecules (FXYD proteins) in the cell membrane, closely associated with the pump, regulate its activity. Methods. We will use a whole-cell patch clamping technique to attach small glass pipettes to single heart cells and replace their content with solutions in the pipettes. The technique allows real-time measurement of Na+-K+ pump activity because the 3:2 Na+:K+ exchange ratio generates an electrical current that can be measured in the single cells. The FXYD proteins will be produced in bacteria, purified and introduced into the heart cells by inclusion in the pipette solution that replace the cell content. Expected outcomes. Achieving this project's objectives will greatly enhance our understanding of Na+-K+ pump regulation. This is important because high levels of Na+ in heart cells is a pivotal abnormality in heart disease. Understanding the Na+-K+ pump can be activated to reduce cell Na+ levels should help design of treatments.Read moreRead less