Objectif Cell cycle progression is monitored by checkpoints that ensure the fidelity of cell division and prevent unrestricted cell proliferation. Checkpoints also serve to couple cell size with division – a mechanism important to adapt to changing environmental conditions.While most studies on cell size homeostasis have focused on the links between size and biosynthetic activity, we have recently discovered a novel geometry-sensing mechanism by which fission yeast cells couple cell length with entry into mitosis. Conceptually, the system is remarkably simple: it is composed of a signal – the protein kinase Pom1 – forming concentration gradients from the ends of the cells, which inhibits a sensor – the protein kinase Cdr2, itself an activator of mitotic entry – placed at the cell equator. Since Pom1 concentration at the cell middle is higher in short cells than in long cells, this suggests a model where Pom1 inhibits Cdr2 until the cell has reached a sufficient length.These findings open a conceptually new way of thinking about cell size homeostasis and suggest that cell polarity and cell shape have important effect on cell cycle progression. The proposed project investigates the mechanisms and functional importance of this geometry-sensing system through four specific aims:Aim 1. Defining and modeling the molecular mechanisms of Pom1 gradient formationAim 2. Dissecting the mechanisms of Pom1 actionAim 3. Investigating the influence of altered cell shape on cell proliferationAim 4. Exploring the effect of environmental stresses to the Pom1-Cdr2 systemBy combining genetic, biochemical, physical, live-imaging and modeling approaches, this project will provide an integrated understanding of how cell geometry can be perceived at the molecular level and how this information is transduced to control cell proliferation. This work will have wide-ranging implication for our understanding of gradient formation, cell size homeostasis, and the role of cell polarity in proliferation. It will thus be of interest to cell, developmental and cancer biologists alike. Champ scientifique natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencescell biologycell polarityengineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsensorsnatural sciencesmathematicspure mathematicsgeometrymedical and health sciencesbasic medicinephysiologyhomeostasis Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-SG-LS3 - ERC Starting Grant - Cellular and Developmental Biology Appel à propositions ERC-2010-StG_20091118 Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil UNIVERSITE DE LAUSANNE Contribution de l’UE € 1 500 000,00 Adresse QUARTIER UNIL CENTRE - BATIMENT UNICENTRE 1015 LAUSANNE Suisse Voir sur la carte Région Schweiz/Suisse/Svizzera Région lémanique Vaud Type d’activité Higher or Secondary Education Establishments Contact administratif Nadine Thomas (Ms.) Chercheur principal Sophie Genevieve Elisabeth Martin Benton (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire UNIVERSITE DE LAUSANNE Suisse Contribution de l’UE € 1 500 000,00 Adresse QUARTIER UNIL CENTRE - BATIMENT UNICENTRE 1015 LAUSANNE Voir sur la carte Région Schweiz/Suisse/Svizzera Région lémanique Vaud Type d’activité Higher or Secondary Education Establishments Contact administratif Nadine Thomas (Ms.) Chercheur principal Sophie Genevieve Elisabeth Martin Benton (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée