Geometric control of the cell cycle in the fission yeast

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 formation

Aim 2. Dissecting the mechanisms of Pom1 action

Aim 3. Investigating the influence of altered cell shape on cell proliferation

Aim 4. Exploring the effect of environmental stresses to the Pom1-Cdr2 system

By 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

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

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 Sitio web

Coste total

Sin datos

Beneficiarios (1)