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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.

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

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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