Project description DEENESFRITPL Profiling the three oscillatory signalling pathways in mouse embryo development Synchronised and rhythmic activity is a hallmark of multicellular organisms. It is evident in phenomena such as circadian oscillators, neural oscillations during sleep and spatiotemporal signalling oscillations during embryonic development. In mouse models of embryonic development, three major signalling pathways have been found to oscillate in activity with a period of about 2 hours. The European Research Council-funded Oscillations project will quantify the activities in these pathways, associated protein dynamics and their interrelationships. The team will use a high tech combination of quantitative real-time imaging, novel ex vivo assays and multimodal functional perturbations to identify how these oscillations emerge and how they modulate developmental patterning in the embryo. Show the project objective Hide the project objective 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. Fields of science natural sciencesbiological sciencescell biologycell signalingnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesdevelopmental biologynatural sciencesphysical sciencesopticsmicroscopymedical and health sciencesclinical medicineembryology Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-StG-2014 - ERC Starting Grant Call for proposal ERC-2014-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Coordinator EUROPEAN MOLECULAR BIOLOGY LABORATORY Net EU contribution € 1 439 919,00 Address Meyerhofstrasse 1 69117 Heidelberg Germany See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all EUROPEAN MOLECULAR BIOLOGY LABORATORY Germany Net EU contribution € 1 439 919,00 Address Meyerhofstrasse 1 69117 Heidelberg See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
