Project description
Modelling the complex interaction of cells in tissues
Tissues are formed during development and comprise different types of cells which maintain a dynamic state of interaction throughout life. Carefully controlled mechanisms are in place to regulate the differentiation, proliferation, and death of these cells. Recent advances in single cell genomics allow the molecular profiling of individual cells within tissues, but cannot decipher the complex interaction between cells. Funded by the European Research Council, the Cells2Tissues project will address this unmet need through mathematical models that describe the dynamic interaction of cell ensembles. The work will integrate epigenetic, signalling and regulatory information to model cell interaction during embryogenesis and in the hematopoietic system.
Objective
One of the most fundamental challenges in contemporary biology is in fact also one of the most classical ones: how to comprehend macroscopic tissue function from the activities of its microscopic cellular components. The remarkable advent of single cell genomics over the last decade is realizing this challenge at unprecedented scales. Measurements of the molecular states of thousands or even millions of cells can now be acquired efficiently, and tools for describing cellular states phenomenologically became well established. But how to model ensemble of cells in tissues is paradoxically even more difficult than before given this new unprecedented experimental resolution. To this end we will develop a new computational and theoretical framework for understanding ensembles of single cells as they interact and dynamically differentiate, proliferate or degrade. Parametric and mechanistic models for defining microscopic cell states over a mathematical manifold will be developed, and the dynamics of ensembles of cells over time and in space will be inferred from new experimental approaches capturing whole tissues over time or within spatially registered domains. Importantly, our models will describe tissues dynamics as change in specific gene regulatory, epigenomic and signaling programs, and we will develop high throughput experiments to combinatorically perturb embryonic and hematopoietic systems in order to test such models extensively. Our research will thereby extend single cell-centric models toward describing dynamics in tissues, with experiments and data collection aiming at rapid translation of the models to actionable and testable strategies for manipulating systems of interest. This will be applied to transparent and epigenetically precise cell type engineering, to discoveries using a unique resource on human hematopoietic ageing and to deep tissue level analysis of combination immunotherapy.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesmolecular biologymolecular genetics
- medical and health sciencesbasic medicineimmunologyimmunotherapy
- natural sciencesbiological sciencesgeneticsepigenetics
- natural sciencesmathematicsapplied mathematicsmathematical model
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Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
ERC - Support for frontier research (ERC)Host institution
7610001 Rehovot
Israel