Project description
Mechanistic insight into neural development
Neural development relies on progenitor cells that make specific decisions to determine cell fate and generate the many cell types of the human brain. Accumulating evidence reveals a remarkable brain cell diversity, but the mechanisms guiding these decisions remain poorly understood and are often assumed to be stochastic. The ERC-funded MOVIOLA project proposes that neural fate choices are largely deterministic and governed by dynamic molecular processes that are largely unexplored. To uncover them, the project introduces an innovative experimental approach that combines live-cell Raman imaging, multi-omics profiling and engineered molecular tags on proteins. This approach offers the possibility to rewire cell decisions and identify their determinants. Project results are slated to clarify neural specification and improve models and therapies.
Objective
The developing nervous system generates an extraordinary diversity of cell types through a series of critical fate decisions made by neural progenitors. Despite recent progress in cataloging the heterogeneity of brain cells, we lack an understanding of the factors orchestrating their fine specification, especially in humans. As a result, many decision processes have uncharacterized determinants and are accounted for as stochastic, leaving us without control over them. This knowledge gap stems from the absence of a systematic approach to capture dynamic moments of cell decision-making and discover the factors controlling them.
I hypothesize that most fate decisions in the human developing nervous system are not stochastic and, instead, depend on many fine-grained, dynamic mechanisms of cell decision-making. However, only a limited number have been characterized, too few to explain the thousands of cell types in the human brain.
To explore this hypothesis, I propose a novel experimental paradigm to elucidate the molecular determinants governing cell decisions. The approach combines live-cell Raman spectrometry imaging, omics profiling, and inducible degrons. I designed it to operate on cell decisions like a film-editing machine, a Moviola: from an outcome, it learns how to “rewind” to a cell’s decision, “halts” the cell and profiles it for decision determinants, and “edits” it to steer it away from the original outcome.
By applying this approach, we expect to find factors influencing fate decisions in human neural specification and reveal a more deterministic control of neural cell fates, illuminating how the vast cellular diversity originates from decision-making events. The insights gained will offer ways to improve in vitro models and cell therapies, with potential implications in the attenuation of neural disorders. This groundbreaking paradigm revolutionizes the study of cell decision-making, with far-reaching implications across diverse fields of biology.
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.
This project's classification has been human-validated.
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.
This project's classification has been human-validated.
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)
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Topic(s)
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-STG
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1015 Lausanne
Switzerland
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