B.1: Formation and Properties of Epithelial and Endothelial Barriers
Participants: Volker Gerke, Hans-Joachim Galla, Uwe Karst, Christian Klämbt, Klaus Langer, Stefan Luschnig, Heymut Omran, Hermann Pavenstädt, Wolfram Pernice, Hans-Joachim Schnittler, Roland Wedlich-Söldner
The establishment of cellular polarity is fundamental to all barrier-forming cells, both in two dimensions when a single cell layer is formed, and in three dimensions when a central lumen is established. Although many molecular determinants required for proper cell polarization are known, the principles that drive the relevant changes in cytoarchitecture leading to a polarized cell layer that develops barrier properties are incompletely understood. These principles will be analysed using cell culture systems and animal models, with emphasis on high resolution microscopic imaging of dynamic cellular processes, including the specific segregation of membrane lipids and proteins, that underlie the establishment of polar epithelial or endothelial barriers and lumen formation. A particular focus will be on a specialized form of the endothelium, the blood-brain barrier (BBB), which guarantees that the CNS is tightly insulated. Genetic screens as well as biophysical approaches will be combined with high resolution imaging and sensitive analytical methods to define the molecular and cellular determinants controlling the formation and maintenance of the BBB, and eventually to develop therapeutic interventions as well as drug delivery approaches for human brain diseases. The combined efforts will help answer the central underlying question of how cellular barriers are established and will aid the development of novel means of penetrating them.