Projektbeschreibung
Die Untersuchung von Top-Down-Interaktionen in verschiedenen biologischen Maßstäben
In verschiedenen biologischen Maßstäben wirken sich neue Eigenschaften der Form und Funktion oft auf Proteine, DNA und RNA aus, die kleinmaßstäbigen Komponenten des zentralen Dogmas der Biologie. Es ist unerlässlich, diese Top-Down-Effekte vorherzusagen und die Komplexität der Bestimmung des Zellschicksals zu ergründen. Zu diesem Zweck wird das EU-finanzierte Projekt CROSSINGSCALES quantitative Bildgebungsmethoden und genomweite Transkriptomik auf Stammzellkulturen und Zebrafisch-Embryos im Frühstadium anwenden. Die Ergebnisse werden einen ganzheitlichen Blick auf die Kern- und Chromatinzustände, die Genexpression, die subzelluläre Organisation und die Organisation auf Gewebeebene von Millionen einzelner Zellen gewähren. Das Projekt wird zum Verständnis der dynamischen, raumzeitlich kontrollierten Interaktion der Genexpression und zellulären Signalgebung beitragen, die die Grundlage allen Lebens bilden.
Ziel
The central dogma in biology often invokes a bottom-up picture of life. However, at different biological scales, new properties in form and function arise that have a superseding causal impact on the behaviour of the lower-scale components from which these new properties emerge. These top-down or reverse scale-crossing effects must be taken into account in order to make predictions about spatiotemporally controlled single-cell fates, activities, levels of gene expression, or the functional outcome of cellular signalling. They can stem from the multicellular, the cellular, and the intracellular scale, and can be quantified using multiscale and multiplexed RNA and protein state imaging in combination with computer vision and data-driven modelling. The ability to comprehensively map these reverse causal effects across multiple scales has the potential to revolutionize most, if not all domains of biology and medicine. In this project, we will establish the importance of reverse causal effects in human induced pluripotent stem cells and early D. rerio embryos. To achieve this, we will develop a quantitative imaging method beyond the diffraction limit of light without compromising scalability in temporal and spatial dimensions. We will also develop a method that achieves scalable, transcriptome-wide image-based multiplexing of mRNA transcripts, and we will extend our computer vision approaches to higher resolution and to three spatial dimensions. These methods will be systematically applied to stem cell collectives grown in 2D and 3D, as well as to early embryos, achieving comprehensive quantification of nuclear and chromatin states, gene expression, subcellular organization, cellular states, and tissue-scale organization across millions of individual cells within the same dataset. These datasets will be used to quantify how, at different scales, new properties in form and function arise that have a superseding causal impact on the behaviour of the lower-scale components
Wissenschaftliches Gebiet
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencescomputer and information sciencesartificial intelligencecomputer vision
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- natural sciencesbiological sciencesgeneticsRNA
- medical and health sciencesclinical medicineembryology
Schlüsselbegriffe
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-ADG - Advanced GrantGastgebende Einrichtung
8006 Zurich
Schweiz