Understanding collective mechanisms of cell fate regulation using single-cell genomics: AHH-OMICS

Programme(s): H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)

Topic(s): ERC-2020-STG - ERC STARTING GRANTS

Call for proposal: ERC-2020-STG

Funding Scheme: ERC-STG - Starting Grant

Grant agreement ID: 950349

Project description

Insight into cell fate regulation

Molecular interactions shape cell behaviour and determine biological functions. Advances in single-cell technologies offer the opportunity to probe these processes with the resolution of single molecules. Scientists of the EU-funded AHH-OMICS project are interested in how these technologies can be used to understand self-organisation processes underlying the behaviour of cells. They will combine single-cell technologies with tools from theoretical physics to study epigenetics and gene expression processes occurring during cellular differentiation, reprogramming and ageing. Their work will overcome important conceptual limitations in an emerging technology in biology.

Objective

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 the proposed research endeavour, we will combine the possibilities of novel single-cell technologies with methods from non-equilibrium statistical physics to understand collective processes regulating cellular behaviour. Using this conceptually new approach, we will 1) unveil collective epigenetic processes during differentiation, reprogramming and ageing, 2) determine how the interplay between different layers of regulation leads to the emergence of mesoscopic spatio-temporal structures in vivo, and 3) understand universal fluctuations in gene expression to unveil mechanistic principles of cellular decisions. Our theoretical work will be challenged by single-cell sequencing experiments performed by our collaborators. We will overcome important conceptual limitations in an emerging technology in biology and pioneer the application of methods from non-equilibrium statistical physics to single-cell genomics. At the same time, we take an interdisciplinary approach to tackle questions at the frontier of non-equilibrium physics.