We use genetic, cell biological and biochemical approaches in Drosophila to study the development of cell polarity. Cell polarity reflects the molecular, morphological and functional asymmetries of a cell. Pronounced cell polarity can be seen in virtually all eukaryote cells, and establishing proper cell polarity is essential for cellular morphogenesis, cell function and tissue integrity. In particular, epithelial cells develop so-called apical-basal polarity by partitioning the cell surface into distinct apical and basolateral domains through polarized formation of cell junctions. Establishing and maintaining apical-basal polarity is crucial for the function and structure of epithelia, while loss of such cell polarity often accompanies the malignant transformation of epithelial cells.
In recent years, a small group of highly conserved "polarity proteins" have been identified for their essential roles in regulating the cell polarity in both vertebrates and invertebrates, and more than half of these polarity proteins were originally discovered in Drosophila. However, the molecular and cellular mechanisms underlying their polarity-regulating functions remain largely obscure. Drosophila epithelial cells provide an excellent model system for studying the apical-basal polarity development. Identifying potential interactions between polarity proteins and established cellular pathways such as vesicle trafficking may be crucial for us to understand how polarity proteins control the establishment and maintenance of epithelial polarity.
We are also highly interested in developing efficient genetic tools that make it possible for us to dissect intricate protein interaction networks, such as polarity protein pathways, by rigorous genetic, cell biological and biochemical assays. Currently we are focusing on optimizing and further developing the ends-out gene targeting routine in Drosophila. We have made major progress to significantly increase the efficiency of ends-out gene targeting. We are using gene targeting as a major approach to generate directedly modified alleles of polarity protein genes in Drosophila.