Descripción del proyecto
Estudio de las interacciones ascendentes a diferentes escalas biológicas
A distintas escalas biológicas, las nuevas propiedades de forma y función suelen repercutir en las proteínas, el ADN y el ARN, los componentes de menor escala del dogma principal de la biología. Es importante cuantificar estos ascendentes para predecir y comprender la complejidad de la determinación del destino celular. Con tal fin, el equipo del proyecto financiado con fondos europeos CROSSINGSCALES aplicará imágenes cuantitativas y transcriptómicas de todo el genoma en cultivos de células madre y embriones de pez cebra en fases tempranas. Con los resultados se creará una visión holística de los estados nucleares y de la cromatina, la expresión genética, la organización subcelular y la organización a escala de los tejidos a través de millones de células individuales. El proyecto contribuirá a la comprensión de la interacción dinámica, controlada espaciotemporalmente, de la expresión genética y la señalización celular que impulsan la vida tal como la conocemos.
Objetivo
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
Ámbito científico
- 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
Palabras clave
Programa(s)
Régimen de financiación
ERC-ADG - Advanced GrantInstitución de acogida
8006 Zurich
Suiza