Objective
Translation of the genetic code into functional proteins is a fundamental biological process essential for cell survival and function. tRNAs are critical in this process because they recognize the codons on the messenger RNA and bring the cognate amino acid to the nascent peptide. To become functional, tRNAs undergo a series of processing steps and chemical modifications. Recently, my host group discovered that cells lacking wobble uridine modifications in the tRNA anticodon display translational slow down, a defect that triggers widespread protein aggregation in yeast and nematodes. These findings were the first to link tRNA metabolism to protein quality control and established tRNA metabolism as a novel layer in the regulation of protein homeostasis. However, the mechanisms underlying this phenomenon remain unknown.
My goal is to elucidate how tRNA processing and modifications regulate protein quality control, by integrating genetic, biochemical, transcriptomic, translatomic and proteomic approaches.
- First, I will identify tRNA biosynthesis genes that are critical for protein aggregation, by assessing global protein homeostasis in yeast cells lacking genes required for tRNA processing and modifications.
- Second, I will characterize transcriptome-wide translation by ribosome profiling to determine whether protein aggregation phenotypes are accompanied by translational defect. This will reveal which tRNA processing and modifications are essential for optimal co-translational protein folding.
- Finally, I will use yeast and nematode models of neurodegenerative diseases to test the functional importance of candidate steps of tRNA metabolism in disease-associated protein aggregation.
My project will comprehensively address the link between tRNA metabolism and protein homeostasis. In particular, it will bridge RNA and protein quality control pathways and shed mechanistic insights into neurodegenerative diseases that originate from tRNA dysfunction.
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 protein folding
- natural sciences biological sciences genetics RNA
- natural sciences chemical sciences organic chemistry amines
- medical and health sciences basic medicine physiology homeostasis
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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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF-EF-ST - Standard EF
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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) H2020-MSCA-IF-2016
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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.
3012 BERN
Switzerland
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.