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Oscillations SIGNED

Oscillatory signaling dynamics – a quantitative approach to reveal their origin and function in development

Total Cost €

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EC-Contrib. €

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Partnership

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 Oscillations project word cloud

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

versatility    function    imaging    positioned    patterning    chemical    dimensional    periodic    found    vertebrate    wave    period    oscillatory    ideally    oscillating    assays    protein    impacts    culture    questions    exhibit    functional    dynamic    perturbations    knock    quantification    assembly    customized    read    mesoderm    breakthrough    quantitative    spatiotemporal    oscillators       origin    model    shifted    vivo    fgf    cell    dynamics    mouse    critical    signalling    phenotypic    resolved    multiple    gradients    generates    principal    temporal    oscillations    2d    synchronization    cutting    embryonic    simultaneous    hours    time    self    employ    recapitulates    unprecedented    organization    offers    outstanding    ex    combine    lab    patterns    genetic    reporter    microscopy    simplified    segmentation    notch    suitable    primary    embryo    physical    modal    striking    emerges    assay    reveal    ultradian    wnt    functions    developmental    signaling    segment    lines    molecular    made    edge    context    combination    oscillate   

Project "Oscillations" data sheet

The following table provides information about the project.

Coordinator
EUROPEAN MOLECULAR BIOLOGY LABORATORY 

Organization address
address: Meyerhofstrasse 1
city: HEIDELBERG
postcode: 69117
website: http://www.embl.de

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 Germany [DE]
 Total cost 1˙439˙919 €
 EC max contribution 1˙439˙919 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-09-01   to  2020-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    EUROPEAN MOLECULAR BIOLOGY LABORATORY DE (HEIDELBERG) coordinator 1˙439˙919.00

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 Project objective

This project aims to reveal the origin and principal functions of spatiotemporal signalling oscillations in the context of embryonic development. Vertebrate embryo segmentation offers a particularly suitable context to study an assembly of ultradian, genetic oscillators, which in addition, exhibit striking synchronization that generates periodic, wave-like patterns.

Using the mouse model, in which three major signalling pathways (Wnt, Notch and Fgf) have been found to oscillate in activity with a period of ~2 hours, we aim to address the following key questions: How do signalling gradients control higher-order, spatiotemporal synchronization of genetic oscillators? What is the role of self-organization? What is the function of spatiotemporal signalling dynamics that are phase-shifted between multiple pathways for developmental patterning? To address these challenging questions, we bring together a unique combination of quantitative real-time imaging, novel ex vivo assays and multi-modal, i.e. genetic, chemical and physical functional perturbations.

To this end, we propose to employ customized knock-in reporter mouse lines developed in my lab and cutting edge microscopy for simultaneous quantification of multiple, oscillating signaling pathway activities and protein dynamics. We aim to combine these dynamic quantification with novel functional perturbations which are made possible due to a critical technical breakthrough achieved in my lab: an ex vivo primary cell culture assay that recapitulates mouse mesoderm patterning, including complex oscillatory wave patterns, and segment formation, in a simplified, 2-dimensional (2D) context. This ex vivo assay will allow an unprecedented versatility of (time-resolved) perturbations and simultaneous quantitative, dynamic read-out at both molecular and phenotypic level.

Our approach thus has an outstanding potential and is ideally positioned to reveal how temporal order emerges and impacts on developmental patterning.

 Publications

year authors and title journal last update
List of publications.
2016 Charisios D. Tsiairis, Alexander Aulehla
Self-Organization of Embryonic Genetic Oscillators into Spatiotemporal Wave Patterns
published pages: 656-667, ISSN: 0092-8674, DOI: 10.1016/j.cell.2016.01.028
Cell 164/4 2019-05-29
2018 Katharina F. Sonnen, Volker M. Lauschke, Julia Uraji, Henning J. Falk, Yvonne Petersen, Maja C. Funk, Mathias Beaupeux, Paul François, Christoph A. Merten, Alexander Aulehla
Modulation of Phase Shift between Wnt and Notch Signaling Oscillations Controls Mesoderm Segmentation
published pages: 1079-1090.e12, ISSN: 0092-8674, DOI: 10.1016/j.cell.2018.01.026
Cell 172/5 2019-05-29

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