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Structure and Function of the Bacterial Transformasome

Objective

Natural genetic transformation, first discovered in Streptococcus pneumoniae by Griffith in 1928, is observed in many Gram-negative and Gram-positive bacteria. This process promotes genome plasticity and adaptability. In particular, it enables many human pathogens such as Streptococcus pneumoniae, Staphylococcus aureus or Neisseria gonorrhoeae to acquire resistance to antibiotics and/or to escape vaccines. For natural transformation to occur, bacteria must develop a highly regulated physiological state called competence, during which a multiprotein machinery, designated as the transformasome, is specifically expressed. The transformasome drives the uptake of extracellular DNA and its subsequent integration into the bacterial genome. This intricate system can be divided into three functional entities: the transformation pilus, the DNA entry pore and the recombination apparatus. The architecture and function of the transformasome remains largely elusive. We propose to dissect the structure and function of this system in the human pathogen Streptococcus pneumoniae. We will combine four complementary approaches to attain our goal: (1) Molecular biology and biochemical studies in vitro (2) Structural biology on purified proteins or protein complexes using X-ray crystallography and cryo-electron microscopy (3) Structure-function studies in vitro and in vivo (4) Structural biology in situ using cryo-tomography.
Overall, we believe this ambitious project will provide major insights to understand the molecular basis of bacterial transformation, a fundamental process in bacterial physiology. In addition, this project may provide new strategies to reduce pneumococcal adaptation during infection.

Fields of science (EuroSciVoc)

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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)

Programme(s)

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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.

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.

ERC-COG - Consolidator Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2016-COG

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Host institution

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Net EU contribution

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.

€ 1 896 501,26
Total cost

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.

€ 1 999 920,00

Beneficiaries (2)

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