Objective
Mycobacterium tuberculosis causes human tuberculosis but can also persist for decades as an asymptomatic latent infection. The mechanisms underlying persistence are poorly understood, and the emergence of drug-resistant tuberculosis makes the development of effective new treatments an urgent challenge. Understanding the ability of M. tuberculosis to switch between replicating and non-replicating states during infection and disease is central to the search for improved treatments.
The number of copies of a protein produced by a cell is generally viewed as being determined by the number of mRNA transcripts, but recent findings suggest that ‘specialised ribosomes’ can modify proteome profiles by preferential translation of particular mRNA subsets, particularly in response to stress. mRNA molecules contain specific signals that optimise their interaction with ribosomes; known as leader sequences, these include the Shine-Dalgarno (SD) sequence required for canonical translation initiation in bacteria. I recently demonstrated that M. tuberculosis expresses an unexpected number of leaderless mRNA transcripts that lack the SD sequence. In Escherichia coli, only a few leaderless transcripts have been described and they are selectively translated by specialised ribosomes. I propose to test the hypothesis that differential translation of mRNA subsets contributes to M. tuberculosis persistence and drug susceptibility.
I will investigate the importance of selective translation of leaderless and SD mRNAs in the context of adaptation to stress and drug resistance in M. tuberculosis, using cutting-edge experimental techniques combined with bioinformatic analyses. The proposed project addresses the fundamental systems biology challenge of establishing quantitative correlations between transcriptome and proteome data, and beyond contributing to the rational design of novel treatments to cure tuberculosis, could help to re-shape classical paradigms of bacterial gene regulation.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences basic medicine pharmacology and pharmacy drug discovery
- medical and health sciences basic medicine immunology
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance
- medical and health sciences clinical medicine pneumology tuberculosis
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
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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.1.1. - EXCELLENT SCIENCE - 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.
ERC-STG - Starting Grant
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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) ERC-2014-STG
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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.
WC1E 7HT London
United Kingdom
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.