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CoSpaDD SIGNED

Competition for Space in Development and Diseases

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

CoSpaDD project word cloud

Explore the words cloud of the CoSpaDD project. It provides you a very rough idea of what is the project "CoSpaDD" about.

capacity illustrated proliferation space shown adjusting induce crowding precedes statistics mechanical homeostasis regenerate apoptosis found organs live imaging explore competition activation responsible mechanisms mechanotransduction efficient combine contribution epithelial plasticity notum involve caspase fast eliminated laser normal delamination inputs density populations pupal deformations remarkable sufficient form types neighbours drosophila local death invasion induction quantitative cell despite adjustment tumoural tissues spontaneous confirmed modulation neighbouring region tissue pretumoural developing sensing suggested showed cells unknown genetics adult midline single morphogenesis perturbations drive clones elimination

Project "CoSpaDD" data sheet

The following table provides information about the project.

Coordinator	INSTITUT PASTEUR Organization address address: RUE DU DOCTEUR ROUX 25-28 city: PARIS CEDEX 15 postcode: 75724 website: http://www.pasteur.fr 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	France [FR]
Project website	https://research.pasteur.fr/en/project/erc-2017-stg_cospadd/
Total cost	1˙489˙147 €
EC max contribution	1˙489˙147 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2017-STG
Funding Scheme	ERC-STG
Starting year	2018
Duration (year-month-day)	from 2018-01-01 to 2022-12-31

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	INSTITUT PASTEUR INSTITUT PASTEUR Organization address address: RUE DU DOCTEUR ROUX 25-28 city: PARIS CEDEX 15 postcode: 75724 website: http://www.pasteur.fr contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	FR (PARIS CEDEX 15)	coordinator	1˙489˙147.00

Map

Project objective

Developing tissues have a remarkable plasticity illustrated by their capacity to regenerate and form normal organs despite strong perturbations. This requires the adjustment of single cell behaviour to their neighbours and to tissue scale parameters. The modulation of cell growth and proliferation was suggested to be driven by mechanical inputs, however the mechanisms adjusting cell death are not well known. Recently it was shown that epithelial cells could be eliminated by spontaneous live-cell delamination following an increase of cell density. Studying cell delamination in the midline region of the Drosophila pupal notum, we confirmed that local tissue crowding is necessary and sufficient to drive cell elimination and found that Caspase 3 activation precedes and is required for cell delamination. This suggested that a yet unknown pathway is responsible for crowding sensing and activation of caspase, which does not involve already known mechanical sensing pathways. Moreover, we showed that fast growing clones in the notum could induce neighbouring cell elimination through crowding-induced death. This suggested that crowding-induced death could promote tissue invasion by pretumoural cells. Here we will combine genetics, quantitative live imaging, statistics, laser perturbations and modelling to study crowding-induced death in Drosophila in order to: 1) find single cell deformations responsible for caspase activation; 2) find new pathways responsible for density sensing and apoptosis induction; 3) test their contribution to adult tissue homeostasis, morphogenesis and cell elimination coordination; 4) study the role of crowding induced death during competition between different cell types and tissue invasion 5) Explore theoretically the conditions required for efficient space competition between two cell populations. This project will provide essential information for the understanding of epithelial homeostasis, mechanotransduction and tissue invasion by tumoural cells

Publications

List of publications.
year	authors and title	journal	last update
2019	Alexis Matamoro-Vidal, Romain Levayer Multiple Influences of Mechanical Forces on Cell Competition published pages: R762-R774, ISSN: 0960-9822, DOI: 10.1016/j.cub.2019.06.030	Current Biology 29/15	2019-08-29
2019	Eduardo Moreno, LÃ©o Valon, Florence Levillayer, Romain Levayer Competition for Space Induces Cell Elimination through Compaction-Driven ERK Downregulation published pages: 23-34.e8, ISSN: 0960-9822, DOI: 10.1016/j.cub.2018.11.007	Current Biology 29/1	2019-08-29
2019	Romain Levayer Solid stress, competition for space and cancer: The opposing roles of mechanical cell competition in tumour initiation and growth published pages: , ISSN: 1044-579X, DOI: 10.1016/j.semcancer.2019.05.004	Seminars in Cancer Biology	2019-08-29
2019	LÃ©o Valon, Romain Levayer Dying under pressure: cellular characterisation and in vivo functions of cell death induced by compaction published pages: 51-66, ISSN: 0248-4900, DOI: 10.1111/boc.201800075	Biology of the Cell 111/3	2019-08-29

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