Obiettivo Cell migration is a critical process for embryogenesis, immune cell function and wound healing as well as cancer progression. Most normal cells migrate by protruding the plasma membrane forward through actin polymerization. The formation of a protrusion requires activation of the small GTPase Rac1 that in turn activates the WAVE complex, which induces branched actin networks through the Arp2/3 complex. For efficient cell migration, membrane protrusion at the leading edge must be sustained. Conversely, cells need to retract membrane protrusion to stop cell migration or turn. The tight control of protrusion lifetime and directional persistence is thus critical to fine tune cell migration. At the molecular level, persistence is controlled by positive and negative feedback loops. However, only few of these feedback loops have been identified and almost none has been characterized, in particular in vivo. In a joint effort with two other labs, proteomic screens were used to identify proteins that interact with the WAVE complex and whose interaction is modulated by branched actin. Based on different selection criteria such as their role in actin dynamics in vitro, conservation in fish, and absence of in vivo data, I selected three candidates. I will unravel their in vivo function at different scales, from embryonic development, to cell migration, to membrane protrusion and cytoskeleton dynamics. Actin feedback loops regulating cell migration will be specifically dissected. To do so, I will take advantage of two complementary and well characterized cellular models: endodermal cells and prechordal plate cells. Endodermal cells perform a random walk, while prechordal plate cells exhibit a directed collective migration. This project, which relies on validated unbiased screens and well established cellular models and approaches, will provide new insights in our understanding of actin dynamics regulation and mechanisms that fine tune cell migration. Campo scientifico scienze naturaliscienze biologichebiochimicabiomolecoleproteinescienze naturaliscienze biologichebiologia dello svilupposcienze mediche e della salutemedicina di baseimmunologiascienze mediche e della salutemedicina clinicaoncologia Programma(i) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Argomento(i) MSCA-IF-2018 - Individual Fellowships Invito a presentare proposte H2020-MSCA-IF-2018 Vedi altri progetti per questo bando Meccanismo di finanziamento MSCA-IF-EF-CAR - CAR – Career Restart panel Coordinatore ECOLE POLYTECHNIQUE Contribution nette de l'UE € 295 061,76 Indirizzo Route de saclay 91128 Palaiseau cedex Francia Mostra sulla mappa Regione Ile-de-France Ile-de-France Essonne Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Altri finanziamenti € 0,00
