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CELLFUSION SIGNED

Molecular dissection of the mechanisms of cell-cell fusion in the fission yeast

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Project "CELLFUSION" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITE DE LAUSANNE 

Organization address
address: Quartier Unil-Centre Bâtiment Unicentre
city: LAUSANNE
postcode: 1015
website: www.unil.ch

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Switzerland [CH]
 Project website https://wp.unil.ch/martinlab/research/the-mechanisms-of-cell-cell-fusion/
 Total cost 1˙999˙955 €
 EC max contribution 1˙999˙955 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-10-01   to  2021-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITE DE LAUSANNE CH (LAUSANNE) coordinator 1˙999˙955.00

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 Project objective

Cell fusion is critical for fertilization and development, for instance underlying muscle or bone formation. Cell fusion may also play important roles in regeneration and cancer. A conceptual understanding is emerging that cell fusion requires cell-cell communication, polarization of the cells towards each other, and assembly of a fusion machinery, in which an actin-based structure promotes membrane juxtaposition and fusogenic factors drive membrane fusion. However, in no single system have the molecular nature of all these parts been described, and thus the molecular basis of cell fusion remains poorly understood.

This proposal aims to depict the complete fusion process in a single organism, using the simple yeast model Schizosaccharomyces pombe, which has a long track record of discoveries in fundamental cellular processes. These haploid cells, which fuse to generate a diploid zygote, use highly conserved mechanisms of cell-cell communication (through pheromones and GPCR signaling), cell polarization (centred around the small GTPase Cdc42) and fusion. Indeed, we recently showed that these cells assemble an actin-based fusion structure, dubbed the actin fusion focus. Our five aims probe the molecular nature of, and the links between, signaling, polarization and the fusion machinery from initiation to termination of the process. These are:

1: To define the roles and feedback regulation of Cdc42 during cell fusion 2: To understand the molecular mechanisms of actin fusion focus formation 3: To identify the fusogen(s) promoting membrane fusion 4: To probe the GPCR signal for fusion initiation 5: To define the mechanism of fusion termination

By combining genetic, optogenetic, biochemical, live-imaging, synthetic and modeling approaches, this project will bring a molecular and conceptual understanding of cell fusion. This work will have far-ranging relevance for cell polarization, cytoskeletal organization, cell signalling and communication, and cell fate regulation.

 Publications

year authors and title journal last update
List of publications.
2019 Ingrid Billault-Chaumartin, Sophie G. Martin
Capping Protein Insulates Arp2/3-Assembled Actin Patches from Formins
published pages: 3165-3176.e6, ISSN: 0960-9822, DOI: 10.1016/j.cub.2019.07.088
Current Biology 29/19 2019-11-07
2018 Daniela Gallo Castro, Sophie G. Martin
Differential GAP requirement for Cdc42-GTP polarization during proliferation and sexual reproduction
published pages: 4215-4229, ISSN: 0021-9525, DOI: 10.1083/jcb.201806016
The Journal of Cell Biology 217/12 2019-08-05
2018 Aleksandar Vještica, Laura Merlini, Pedro Junior Nkosi, Sophie G. Martin
Gamete fusion triggers bipartite transcription factor assembly to block re-fertilization
published pages: 397-400, ISSN: 0028-0836, DOI: 10.1038/s41586-018-0407-5
Nature 560/7718 2019-08-05
2018 Bita Khalili, Laura Merlini, Vincent Vincenzetti, Sophie G. Martin, Dimitrios Vavylonis
Exploration and stabilization of Ras1 mating zone: A mechanism with positive and negative feedbacks
published pages: e1006317, ISSN: 1553-7358, DOI: 10.1371/journal.pcbi.1006317
PLOS Computational Biology 14/7 2019-08-05
2017 Omaya Dudin, Laura Merlini, Felipe O. Bendezú, Raphaël Groux, Vincent Vincenzetti, Sophie G. Martin
A systematic screen for morphological abnormalities during fission yeast sexual reproduction identifies a mechanism of actin aster formation for cell fusion
published pages: e1006721, ISSN: 1553-7404, DOI: 10.1371/journal.pgen.1006721
PLOS Genetics 13/4 2019-06-18
2018 Laura Merlini, Bita Khalili, Omaya Dudin, Laetitia Michon, Vincent Vincenzetti, Sophie G. Martin
Inhibition of Ras activity coordinates cell fusion with cell–cell contact during yeast mating
published pages: 1467-1483, ISSN: 0021-9525, DOI: 10.1083/jcb.201708195
The Journal of Cell Biology 217/4 2019-06-18

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