Project description
Extracellular signal perturbations and stem cell fate
Cell differentiation into mature cells with specialised form and function is driven by specific extracellular signals. This is a highly complex process that is regulated with spatial and temporal resolution. Funded by the European Research Council, the i-SignalTrace project aims to predict which signalling pathways are activated in stem cells when subject to different extracellular signals. Researchers will employ the CRISPR/Cas9 gene-editing technology to unveil the mechanisms of cell fate commitment and understand how different perturbations may affect stem cells. The work is expected to provide fundamental knowledge on developmental biology and improve regenerative medicine protocols of cell therapies.
Objective
Understanding the identity and intensity of the specific extracellular signals that a cell experiences at different times during its differentiation is essential to develop advanced cellular therapies. However, uncovering the sequence of these signaling events, their intensities, timing, and relevance in development and disease is proving to be very challenging.
Here, I propose to build i-SignalTrace: a CRISPR/Cas9-based molecular recorder with the capacity to store both lineage information and signalling pathway activity for multiple signals over time in single cells. By performing kinetic experiments and mathematical modeling, I will use i-SignalTrace to extract the probability of signalling pathways to be activated in stem cells when subject to different extracellular signals and reconstruct the lineage tree of pathway activities during differentiation with single-cell resolution. In combination with single-cell RNA sequencing, i-SignalTrace will make it possible to characterize transition and intermediate states along differentiation trajectories, and quantify the integration between extracellular signals and autonomous programs of gene expression. These results will allow predicting the differentiation trajectories that stem cells follow when subject to external perturbations, and deciphering the role of heterogeneity in signalling pathway activity during cell-fate commitment.
Using i-SignalTrace, I will identify missing or redundant signalling pathways induced during in vitro differentiation protocols. Therefore, I expect that exploitation of i-SignalTrace will allow establishing new criteria to design protocols to differentiate stem cells on demand. As a proof-of-concept, I propose a framework to improve the functionality of monolayer-derived cardiomyocytes. Taken together, i- SignalTrace will find applications in both fundamental developmental biology and translational regenerative medicine, which will benefit a much wider scientific community.
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. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2021-STG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
2333 ZA Leiden
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.