Descrizione del progetto
Studio delle interazioni dall’alto verso il basso a diverse scale biologiche
A diverse scale biologiche, nuove proprietà nella forma e nella funzione spesso hanno un impatto sulle proteine, sul DNA e sull’RNA, i componenti di scala inferiore del dogma centrale della biologia. È importante quantificare questi effetti dall’alto verso il basso per prevedere e comprendere la complessità della determinazione del destino cellulare. Per risolvere questo problema, il progetto CROSSINGSCALES, finanziato dall’UE, applicherà l’imaging quantitativo e la trascrittomica dell’intero genoma su colture di cellule staminali ed embrioni precoci di pesce zebra. I risultati creeranno una visione olistica degli stati nucleari e della cromatina, dell’espressione genica, dell’organizzazione subcellulare e dell’organizzazione su scala tissutale attraverso milioni di singole cellule. Il progetto contribuirà alla comprensione dell’interazione dinamica, controllata spazio-temporalmente, dell’espressione genica e della segnalazione cellulare che guidano la vita così come la conosciamo.
Obiettivo
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
Campo scientifico
- 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
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-ADG - Advanced GrantIstituzione ospitante
8006 Zurich
Svizzera