Investigating the molecular basis of basement membrane specialisation and basal surface organisation during epithelial tissue development

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Cells are the building blocks that make up our organs. Our goal is to understand how during development, epithelial cells, which are found in most of our organs, coordinate changes in their shape to generate complex three dimensional structures, including tubes, folds and cavities, vital for organ function. One of the reasons we are interested in epithelial cell and tissue shape control is because abnormal epithelial tissue organisation has been implicated in many diseases, including in colon, stomach, breast, and lung cancer, for example. To uncover how changes in cell shape can be coordinated across a tissue to generate a healthy, functioning epithelial structure, we will use the Drosophila (fruit fly) retina, where we can use a broad range of genetic tools to manipulate the function of candidate molecular machinery involved in cell shape control, while studying the effect these manipulations have on cells and tissue shape in a living animal, as the organ develops. With this powerful approach, we have recently discovered that cells can communicate with each other to coordinate changes in their shape through a molecule called Laminin, a gel-like substance that lines the bottom surface of cells in flies and human alike. Our objective is to further investigate this communication process in a simple animal system and understand how it helps coordinate the changes in cells that shape the tissues in our organs. This knowledge will help us comprehend how epithelial tissues develop in general and we hope, will contribute to better understanding the causes of diseases linked to abnormal epithelial tissue organisation and mutation in Laminins, which have been implicated in a range of pathologies in humans.