Understanding collective mechanisms of cell fate regulation using single-cell genomics

Informations projet

AHH-OMICS

N° de convention de subvention: 950349

DOI

10.3030/950349

Date de signature de la CE 13 Novembre 2020

Date de début 1 Janvier 2021

Date de fin 31 Decembre 2026

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 1 489 500,00

Contribution de l’UE

€ 1 489 500,00

Coordonné par

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Germany

Periodic Reporting for period 3 - AHH-OMICS (Understanding collective mechanisms of cell fate regulation using single-cell genomics)

Période du rapport: 2024-04-01 au 2025-12-31

Résumé du contexte et des objectifs généraux du projet

Biological systems rely on an influx of energy to build and maintain complex spatio-temporal structures. A striking example of this is the self-organisation of cells into tissues, which relies on an interplay of molecular programs and tissue-level feedback. The mechanistic basis underlying these processes is poorly understood. The recent advent of single-cell sequencing technologies for the first time gives the opportunity to probe these processes with unprecedented molecular resolution in vivo. Biological function, however, relies on collective processes on the cellular scale which emerge from many interactions on the microscopic scale. But what can we learn about such collective processes from detailed empirical information on the molecular scale?

Concepts from non-equilibrium statistical physics provide a powerful framework to understand collective processes underlying the self-organisation of cells. In this research endeavour, we combine the possibilities of novel single-cell technologies with methods from non-equilibrium statistical physics to unveil collective processes regulating cellular behaviour. We apply the theories developed in this research to the regulation of cellular behaviour during embryonic development, regeneration and ageing.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

While single-cell sequencing technologies usually give detailed molecular descriptions along the linear DNA sequence, the processes that are important for the behavior of cells occur in space and time and rely on interactions between many positions in the genome. We developed theoretical methodology that allows for the inference of spatio-temporal processes from measurements along the linear DNA sequence. We applied these theories to unveil the molecular processes underlying epigenetic regulation in development and ageing.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

In this project, we developed conceptually new theoretical approaches to understand collective, molecular phenomena in biological systems. We expect that this approach will give rise to a new perspective on important biological processes underlying development, ageing and regeneration.

Heatmap showing data from a single-cell sequencing experiment.