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i-SignalTrace

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Deciphering signalling pathway dynamics during cell-fate commitment in stem cell...

Deciphering signalling pathway dynamics during cell-fate commitment in stem cells 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 sequ... ver más

29/02/2028

Leiden University...

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

ACADEMISCH ZIEKENHUIS LEIDEN No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-03-01

ERC-2021-STG: ERC STARTING GRANTS Scope:Objectives

I+D

Cerrada hace 3 años

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No hay información privada compartida para este proyecto. Habla con el coordinador.

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Leiden University Medical Ce...

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Duración del proyecto: 59 meses Fecha Inicio: 2023-03-01
Fecha Fin: 2028-02-29

Líder del proyecto

ACADEMISCH ZIEKENHUIS LEIDEN No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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.

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