Project description DEENESFRITPL The unassuming sea urchin sheds light on the evolution of development and its regulators Development is a complex and highly regulated process. Among the regulators of gene expression are DNA regulatory elements like promoters and enhancers. Mutations in regulators play a role not only in disease states but also in evolution of new morphologies. In this way, understanding the evolution of developmental gene regulatory networks is a critical piece of the development puzzle. The EU-funded evolSingleCellGRN project is applying advanced single-cell methodologies in the sea urchin, including a recently developed assay of chromatin accessibility (ATAC-Seq) that points to areas 'open' to binding and thus regulation. It facilitates the study of epigenetic modifications on a genome-wide scale. Identifying tissue-specific regulatory elements and evaluating effects when they are mutated should shed light on how development evolves. Show the project objective Hide the project objective Objective Cell types in development arise from precise patterns of gene expression driven by differential usage of DNA regulatory elements. Mutations affecting these elements, or proteins binding them, are major contributors to disease and underlie the evolution of new morphologies. To better understand these elements and how they evolve, I introduce a set of single-cell RNA and ATAC-Seq sequencing technologies that: A) Identify tissue-specific regulatory elements and expression profiles by interrogating individual cells, B) Allow for a precise read-out of developmental responses to mutation and perturbation, including cell-fate re-specification, C) Lead to the development of a regulatory-information based concept of homology that will be used to understand developmental evolution. The research makes use of sea urchins. The well-annotated sea urchin regulatory network, a detailed understanding of inductive interactions in early development, and an active body of evolutionary research justify this choice. Using single-cell ATAC-Seq and a new method for resolving single-cell, nascent transcripts, I will build a detailed atlas of sea urchin development and use this atlas to understand how regulatory landscapes change during specification and how they evolve between closely related species. I will also investigate, at single-cell resolution, how larval skeletal cells are regenerated following the loss of a cell lineage that mirrors euechinoid evolution. To better understand the origins of cell types in sea urchins, I will characterize embryos of the cnidarian Nematostella, using shared regulatory sites to define cell types which I will compare to urchins and my previous work in Drosophila. The work will generate single-cell methods for non-traditional model systems and help to resolve the processes by which, and the paths along which, development evolves. Fields of science natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsmutationnatural sciencesbiological sciencesgeneticsRNAmedical and health sciencesclinical medicineembryology Keywords single-cell Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2018-STG - ERC Starting Grant Call for proposal ERC-2018-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Host institution HUMBOLDT-UNIVERSITAET ZU BERLIN Net EU contribution € 1 499 900,00 Address UNTER DEN LINDEN 6 10117 Berlin Germany See on map Region Berlin Berlin Berlin Activity type Higher or Secondary Education Establishments 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 Total cost € 1 499 900,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all HUMBOLDT-UNIVERSITAET ZU BERLIN Germany Net EU contribution € 1 499 900,00 Address UNTER DEN LINDEN 6 10117 Berlin See on map Region Berlin Berlin Berlin Activity type Higher or Secondary Education Establishments 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 Total cost € 1 499 900,00