Adherens junctions (AJ) play key roles in cell-cell adhesion, cell migration and cell signaling in a variety of biological processes. AJ are dynamic structures composed of cell-cell adhesion proteins (cadherin super-family), associated adaptor proteins (alpha-, and beta-catenin) and other proteins (p120) that locally regulate the actin cytoskeleton. The functions of two components of the AJ, cadherins and beta-catenin, are well understood, but the function of alpha-catenin is not. Significantly, Professor Nelson’s laboratory identified new functions for alpha-catenin that may be particularly important during cell rearrangements. An important, unanswered question is how these AJ are regulated during complex cell rearrangements when cell-cell contacts are maintained as cells migrate. We propose to combine classical zebrafish methodologies with cell biochemical and biophysical approaches, and high resolution live cell imaging to define mechanisms underlying epithelial cell rearrangements driven by remodeling and stabilization of AJ during different phases of zebrafish development. This project embodies a unique research plan for the candidate in which he will examine the dynamics of cell adhesion and migration in zebrafish embryogenesis by initially applying biochemical and cell biology strategies developed in Professor Nelson’s laboratory at Stanford University, and subsequently use biophysical, imaging and genetic methods developed in Dr. Gilmour’s laboratory at the EMBL. Zebrafish is an established model system for genetics and development biology, and is emerging as model for cell biology studies; this project proposes to push these boundaries further by using strategies developed from biochemical and biophysical studies. The overall aim of the project is, therefore, to provide a novel training platform for the Fellow, Dr. Schepis, using different experimental approaches provided by the Nelson and Gilmour laboratories.
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