Project description
Exploring translational specialisation factors’ role in cardiac diseases
How genetic information is translated into cell fate decisions is a central question in developmental biology. The ERC-funded TRANSCEND project investigates how cells selectively control protein production over time and space to drive human heart development. Focusing on specialised regulators of translation, the project will uncover how these factors shape key developmental transitions and guide cardiac cell identity and function. It will combine cutting-edge experimental and computational approaches to map translational control programmes in health and disease and to test whether they can be harnessed to counter pathological cardiac remodelling. The findings will contribute to the development of innovative therapies to restore cardiac function.
Objective
A central question in developmental biology is how the genetic information is differentially interpreted to program cell-fate decisions essential for embryogenesis. The success of developmental cell-fate decisions relies on the accurate rewiring of the proteome to support rapid cellular identity changes. Here, we will address the fundamental question: How is the developmental transcriptome differentially translated in time and space to program cell-fate decisions? I hypothesize that the developmental competence for cell-fate decisions is controlled by fate-specific translational specialization factors (TSFs). TSFs program the selective and privileged translation of developmental genes in defined time windows to enable the acquisition of cell fate and maintenance of cellular identity. Notably, in a proof-of-principle study, we discovered that translational specialization in pluripotency poises future lineage choices in humans. The research program TRANSCEND has four work packages: (1) identifying candidate TSFs engineering cardiac fate at critical cell-fate transitions by cell-fate specific, systematic cataloging TSFs on ribosomal complexes; (2) dissecting the molecular and functional role of TSFs in cardiac cell-fate specification by combining targeted CRISPR screens and tethered functional approaches; (3) decoding the mechanisms, modalities, and design principles by which TSFs program cardiac identity by using a holistic approach, including loss-of-function studies in cardiac 2D, organoid, and mouse models along with systems-wide methods such as eCLIP-seq and TCP-seq; and (4) engineering translation specialization modules to ameliorate pathological cardiac hypertrophy using patient-derived in vitro and murine in vivo models. Ultimately, the proposed research program TRANSCEND aims at transforming our current understanding of translational control over cell-fate decisions and opening up innovative avenues for controlled therapeutic restoration of cardiac function.
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.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences biological sciences developmental biology
- natural sciences biological sciences genetics RNA transcriptomes
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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)
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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.
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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-2021-COG
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60323 Frankfurt Am Main
Germany
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