Objetivo 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. Ámbito científico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencescell biologycell polarityengineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsensorsnatural sciencesmathematicspure mathematicsgeometrymedical and health sciencesbasic medicinephysiologyhomeostasis Programa(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) Tema(s) ERC-SG-LS3 - ERC Starting Grant - Cellular and Developmental Biology Convocatoria de propuestas ERC-2010-StG_20091118 Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-SG - ERC Starting Grant Institución de acogida UNIVERSITE DE LAUSANNE Aportación de la UE € 1 500 000,00 Dirección QUARTIER UNIL CENTRE - BATIMENT UNICENTRE 1015 LAUSANNE Suiza Ver en el mapa Región Schweiz/Suisse/Svizzera Région lémanique Vaud Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Nadine Thomas (Ms.) Investigador principal Sophie Genevieve Elisabeth Martin Benton (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo UNIVERSITE DE LAUSANNE Suiza Aportación de la UE € 1 500 000,00 Dirección QUARTIER UNIL CENTRE - BATIMENT UNICENTRE 1015 LAUSANNE Ver en el mapa Región Schweiz/Suisse/Svizzera Région lémanique Vaud Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Nadine Thomas (Ms.) Investigador principal Sophie Genevieve Elisabeth Martin Benton (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos