Cargo selective apical transport and epithelial polarity

Epithelial cells are the foundation of many different organs in our body. To accomplish various specialized functions within organs, epithelial cells are polarized. This means, that the outer surface of the cells, the so-called plasma membrane, differs in its composition and function between the top and the bottom of the cell. In order for this to function properly, transport of proteins in the inner of the cell needs to be correctly directed towards the plasma membrane. Disturbances in this delicate interplay, caused by genetic defects for example, may lead to disease. Researching these diseases has contributed to the understanding of many cellular mechanisms. Novel technologies, such as CRISPR/Cas9 genome editing, allow the modification or silencing of many genes. We make use of this possibility to systematically silence every gene in intestinal epithelial cells. At the same time, we test the surface of these epithelial cells for the presence of a certain marker protein, which requires intact surface delivery from the inner of the cell. Next, we collect cells with missing surface marker protein and search for silenced gene by CRISPR/Cas9. With this approach, we can study all known genes of the human genome on their role in proper epithelial cell function. Genes with yet unknown function in epithelial cells will be studied and characterized by further experiments to enhance the understanding of epithelial cells and function. Ideally, this helps us to better understand inborn diseases affecting epithelial cells. This project will be carried out by two PhD-students in a period of four years.