The team of Grégory Giannone (Interdisciplinary Institute for NeuroScience, CNRS / University of Bordeaux, France) and the team of Nicolas Brown (University of Cambridge, United Kingdom) obtained a 2017 award for Research Grant from the Human Frontier Science Program (HFSP). The aim of this project is to understand the dynamic rearrangement of protein interactions within macromolecular complexes in vivo. For that they will combine Grégory Giannone’s expertise in live super-resolution microscopy with Nicolas Brown’s expertise in Drosophila developmental genetics. They will advance existing methods to achieve the challenging task of quantitative super-resolution imaging within Integrin adhesion complexes in living Drosophila tissues.
Integrin adhesion complexes (IACs) provide a paradigm for a distinctive class of subcellular protein complex. Rather than assembling a structure of fixed stoichiometry (e.g. ribosome, centriole) via exclusive interactions, evidence is emerging that IACs engage a dynamic set of heterogeneous interactions that evolve from IAC initiation through maturation to achieve their signaling and mechanical functions. Thus, we hypothesize that a key feature of IACs is their ability to exchange multivalent interactions between components, so changing their composition in response to diverse inputs, including force, developmental history and location within the organism. To test this hypothesis we will combine Grégory Giannone’s expertise in live super-resolution microscopy with Nicolas Brown’s expertise in Drosophila developmental genetics. First we will advance existing methods to achieve the challenging task of quantitative super-resolution imaging within IACs in living tissues. Second, we will develop new tools to image interacting proteins, study their dynamic behavior and alter the interactions. Discovering the regulation of IAC rearrangement will greatly improve our understanding not only of mechanisms mediating Integrin adhesion but also of dynamic macromolecular protein complexes.