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

Project Information

AHH-OMICS

Grant agreement ID: 950349

DOI

10.3030/950349

EC signature date 13 November 2020

Start date 1 January 2021

End date 31 December 2026

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 489 500,00

EU contribution

€ 1 489 500,00

Coordinated by

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Germany

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

Reporting period: 2024-04-01 to 2025-12-31

Summary of the context and overall objectives of the project

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.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

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.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

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.