ERC Advanced Grant

The regulation of cell migration is central in pattern formation, homeostasis and disease. The proposed research is aimed at investigating the molecular basis for cell motility and the associated polarization of the cell. In view of the dynamic nature of these processes, we have chosen to utilize the migration of Primoridal Germ Cells (PGCs) in zebrafish - a model that offers unique experimental advantages for imaging and experimental manipulations. The fact that molecules facilitating the motility of zebrafish PGCs are evolutionary conserved and the finding that the cells are directed by chemokines, molecules that control a wide range of cell trafficking events in vertebrates, make this in vivo study of particular importance.The proposed work involves both the functional analysis of previously identified candidates and the identification of molecules, which have a presently unknown effect on the migration process. For both objectives, we will employ novel experimental schemes. We will examine the role of proteins in achieving functional cell polarity compatible with efficient motility and response to directional cues, using unique techniques and analysis tools in the context of the living organism. The precise function of the identified proteins will be determined by combining mathematical tools aimed at quantitatively gauging the role of the molecules in conferring proper cell shape, biophysical methods aimed at measuring forces, rigidity and cytoplasm flow and determination of the effect on the organization of relevant structures using cryo electron tomography.Together, this approach would provide a non-conventional understanding of cell migration by correlating structural, morphological and dynamic cellular properties with the ability of cells to effectively migrate towards their target.