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Amanda Goodwin: Targeting Myofibroblast Mechanotransduction to prevent Pulmonary Fibrosis


Idiopathic pulmonary fibrosis (IPF) is a long-term chest condition that is characterised by fibrosis (scarring) of the lungs, which reduces the ability of the lungs to take in oxygen. IPF causes significant symptoms, is progressive, and has no cure, making it an important disease to research. However, it is not clear why some people develop IPF.


In IPF, the lungs become small and stiff due to the abnormally high activity of cells that make scar tissue. Studies have shown that this scarring begins in the areas of the lung that are being stretched the most during breathing. Research has also shown that when cells grow in stiff surroundings, like that within scarred lung, they become even more active and produce more scar tissue. We also know that lung injury causes the release of a chemical called lysophosphatidic acid (LPA), which causes many events that lead to lung scarring.

G proteins are a group of proteins that are "switched on" by sensing molecules on the cell surface (G protein-coupled receptors, GPCRs) and pass on this information by activating other molecule inside the cell, controlling which genes are switched on and which proteins are made. We know that two families of G-protein (Ga12/13 family and Gaq/11 family) pass on signals that lead to lung scarring. Both groups of G proteins can be switched on by mechanical forces, although the mechanical forces transmitted by these two groups may be different.

The aim of this project is to find out precisely how the Ga12/13 and Gaq/11 families sense different types of mechanical signals (stretch and stiffness of surroundings) and cell injury signals, and how these cause lung scarring. To do this, I will compare how the Ga12/13 and Gaq/11 protein families react to injury, cell stretch and changes in matrix stiffness with cells that don't have Ga12/13 or Gaq/11.

I will also look into whether cells from people with and without IPF have different amounts of Ga12/13 and Gaq/11 activity. In addition, I will use a model of pulmonary fibrosis where the scar producing cells do not have the Ga12/13 or Gaq/11 family of proteins, and measure how the absence of these proteins affects the development of fibrosis in the lung.

From these experiments, I hope to learn more about the reasons behind how and why IPF develops. The molecules or proteins that I find to be important for the development of IPF may also be good targets for new treatments. Therefore, this project will increase what we know about why IPF develops, and may help us to find a cure for IPF

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