Project description DEENESFRITPL Mapping the developmental process of Platynereis dumerilii All cells in multicellular organisms are descendants of the same totipotent zygote, committed to a subset of expression programmes in the course of development. The stepwise reduction of differentiation potential is described as Waddington’s epigenetic landscape or Waddington lineage. The specific gene expression cell programmes are governed by transcription factors and the effector genes that give rise to the cellular phenotype. Funded by the Marie Skłodowska-Curie Actions programme, the DeCoDe Platy project aims to reconstruct the Waddington lineage of model organism Platynereis dumerilii using single-cell RNA-sequencing and chromatin accessibility data for multiple developmental stages. The goal is to create a map that connects gene expression with the subcellular morphology and locations in the animal body. Show the project objective Hide the project objective Objective Cells in multicellular organisms show a huge diversity of shape, size, and function, yet are all descended from the same totipotent zygote. As development progresses, cells lose their ability to contribute to different fates, instead committing to a narrower subset of expression programs. This stepwise reduction of differentiation potential has been illustrated in Waddington’s epigenetic landscape (“Waddington lineage”). The specific gene expression programs of cell types are governed by Core Regulatory Complexes (CoRCs), where transcription factors cooperate to maintain their own expression and the effector genes that give rise to the cellular phenotype. Cell types exist as terminal or transitory states of the Waddington lineage, and it is yet unclear whether and to what extent transitory developmental and terminal cell types involve similar or distinct regulatory principles and effector modules.I will reconstruct the Waddington lineage of Platynereis dumerilii, an indirectly developing marine invertebrate with a wealth of transitory developmental and terminal cell types. I will gather single-cell RNA-seq and chromatin accessibility data for multiple developmental stages and computationally identify putative cell types. I will map these onto locations in the animal body using the in-situ expression patterns of lineage and cell type markers, and exploit unique electron microscopy data to explore the connection between gene expression and subcellular morphology. After connecting successive stages computationally, I will validate the resulting Waddington lineage with functional experiments, disrupting the expression of effector genes in the terminal cell types with CRISPR/Cas9.By combining gene expression, chromatin accessibility, cellular lineage information, functional genomics, spatial localization, and, uniquely, subcellular morphology, we will shed light on animal development and the regulatory mechanisms that govern cell types. Fields of science natural sciencesbiological sciencescell biologycell signalingnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesdevelopmental biologynatural sciencesphysical sciencesopticsmicroscopyelectron microscopynatural sciencesbiological sciencesgeneticsepigenetics Keywords DeCoDe Platy Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2020 - Individual Fellowships Call for proposal H2020-MSCA-IF-2020 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator EUROPEAN MOLECULAR BIOLOGY LABORATORY Net EU contribution € 174 806,40 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
