Objective
In eukaryotes, the spliceosome removes non-coding introns from precursor messenger RNAs during pre-mRNA splicing. Crucially, many pre-mRNAs are spliced differently depending on cellular status or external stimuli. This “alternative splicing” reshapes the genetic information from a given mRNA to encode several protein isoforms and greatly diversifies proteomes.
Splicing must be extremely precise as errors produce aberrant mRNA encoding potentially toxic proteins. Splicing fidelity relies on the accuracy of the spliceosome that assembles de novo on each pre-mRNA in a cotranscriptional manner, gets activated and selects the precise boundaries of introns to catalyse their excision. The spliceosome is endowed with two apparently conflicting properties: it must be very accurate to avoid splicing errors while being tolerant to accommodate alternative splicing changes. I. aim to unveil the molecular basis of splicing fidelity’s enforcement and modulation by the spliceosome.
Due to its extreme complexity, the spliceosome has long been a major challenge for molecular and structural investigations. Recent progresses in cryo-EM allow the structural analysis of very dynamic and low-abundance biological objects such as spliceosomes. Hence, it is now possible to explore the most elusive aspects of RNA splicing, provided that the biochemical challenges of trapping and stabilising transient spliceosome intermediates are overcome beforehand.
I will use innovative methods to capture spliceosomes from cell extracts and cryo-EM to investigate how splicing fidelity is:
• enforced by molecular checkpoints during spliceosome activation
• maintained/modulated by other cellular processes
• impaired during viral infection
The outcome of this research will bring us closer to answering a fundamental question of biology: how does the spliceosome give rise to the immense combinatorial space of alternative splicing without errors and allow the 20,000 human genes to yield 200,000 proteins.
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)
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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-2022-STG
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75794 PARIS
France
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