Project description DEENESFRITPL It’s all about timing: the paradigm of embryonic development Embryonic development begins after fertilisation and undergoes the same stages in many species, at however different paces depending on the organism. The underlying aetiology of the differences in developmental time between species remains unclear. The working hypothesis of the EU-funded ALLOCHRONY project is that this developmental allochrony is due to different rates in key biochemical reactions. Researchers will develop organoids from pluripotent stem cells that mimic early embryogenesis to study key reactions in mouse and human cells. Results will advance existing knowledge on embryonic development and identify the rate-limiting steps in the process. Show the project objective Hide the project objective Objective While the mechanisms of embryonic development are well conserved, the progression speed differs among animal species. The molecular cause of ‘allochrony’, interspecies differences in developmental tempo, remains unclear due to lack of an appropriate experimental model. In vitro differentiation of pluripotent stem cells (PSCs) offers unique opportunities to compare the same cell type among diverse species in a similar condition. We have previously recapitulated the oscillatory gene expression of the segmentation clock with PSCs, demonstrating ~2 hour and ~5 hour oscillation periods in murine and human induced presomitic mesoderm (PSM) cells, respectively. We have further found that the period difference stems from differential biochemical reaction speeds of HES7, a core segmentation clock gene, between the species: human PSM cells show slower degradation rates of HES7 and longer delays in its production processes than mouse cells. Here we aim to investigate the deeper origin of developmental allochrony, the molecular mechanism by which human cells exhibit slower biochemical reactions. We will systematically and quantitatively measure the degradation rates and delays to reveal commonalities of the genes that show differential reaction speeds between murine and human cells (Aim 1). In parallel, we will test two working hypotheses that nuclear/cytoplasmic transport rates or metabolic rates might be lower in human cells, which should lead to slower biochemical reactions (Aim 2). The other objective is to test the universality of the mechanism of allochrony. We will create gastruloids, organoids mimicking early embryogenesis, from PSCs of diverse mammalian species to investigate what cell types, in addition to PSM cells, and what species exhibit the differential biochemical reaction speeds (Aim 3). This study will tackle a fundamental question in biology by using quantitative, cutting-edge technologies, ultimately enabling manipulation of developmental time. Fields of science natural sciencesbiological sciencesdevelopmental biologymedical and health sciencesmedical biotechnologycells technologiesstem cells Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2020-COG - ERC CONSOLIDATOR GRANTS Call for proposal ERC-2020-COG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Coordinator EUROPEAN MOLECULAR BIOLOGY LABORATORY Net EU contribution € 1 987 447,00 Address Meyerhofstrasse 1 69117 Heidelberg Germany See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis 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 € 1 987 447,00 Address Meyerhofstrasse 1 69117 Heidelberg See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis 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
