Coordinating the remodelling of cell polarity to form a functional organ.

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The cells that make up our tissues adopt complex shapes. In most cases, each cell is able to do part of this process autonomously by defining an intrinsic polarity axis, so they know which end is up and which end is down. For epithelial cells, which line most of our organs, one end must point to the inside and one to the outside. This is true for all organs, and in epithelia is important because it underpins their function in absorbing nutrients (intestine), oxygen (lung) or filtering out salts and toxins (kidney or liver). Loss of polarity affects tissue health and the ability of epithelial cells to adhere to one another, which in turn can lead to cancer cells escaping a tissue to invade another through the process of metastasis. The aim of this programme is to figure out the mechanisms that induce polarised organisation of individual cells, and to determine how these cells work together to form complex multicellular structures in 3D. These structures can consist of cells that arrange themselves into layers found one on top of another, as in the skin or oesophagus, for example. How such tissue organisation is created is not well understood and will be studied with this research grant. Recent work in our laboratory has identified factors that are required for epithelial polarity, some of which have been previously linked to human pathologies. Our results also indicate that mechanical forces might play an essential role in coordinating polarity between cells, as they assemble into a tissue. In summary, we aim to elucidate how cells work together to induce polarised organisation of a complex animal tissue in health and disease.