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Deciphering the molecular architecture and infection mechanisms of corynephages within native host environments

Objective

Antibiotic resistance is a major global health threat, creating an urgent need for alternative therapeutics. Phages, viruses that infect and kill bacteria, are promising candidates, but their biomedical use requires detailed knowledge of infection and replication mechanisms at atomic resolution. Corynephages infect bacteria of the Corynebacteriales order, including important pathogens such as Corynebacterium diphtheriae and Mycobacterium tuberculosis. Despite their relevance, these phages remain entirely unexplored at the structural and molecular level. Their fragile and flexible structure has so far prevented structural studies using cryo-electron microscopy (cryo-EM).

The ISPHAGE project aims to overcome these limitations and determine, for the first time, the complete atomic structure of a corynephage. This will deliver unprecedented insights into their infection strategies and replication cycle in the natural host. To achieve this, I will establish an integrated cryo-EM pipeline combining single particle analysis (SPA), cryo-electron tomography (cryo-ET), subtomogram averaging (STA), and cryo-focused ion beam (cryo-FIB) milling. Furthermore, I will implement innovative computational approaches to address protein flexibility during STA, currently a major barrier to achieving high resolution in cryo-ET.

By delivering the first de novo atomic details of corynephages and visualizing infection events in situ, ISPHAGE will significantly advance our understanding of phage biology. The project will strengthen my career as an independent investigator through advanced training and knowledge transfer, while paving the way for innovative antibacterial strategies. In this way, ISPHAGE will contribute both to fundamental science and to the global fight against antimicrobial resistance, a critical priority for Europe and worldwide health.

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.

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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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) HORIZON-MSCA-2025-PF

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Coordinator

UNIVERSITE DE LAUSANNE
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.

€ 292 118,88
Address
QUARTIER UNIL CENTRE - BATIMENT UNICENTRE
1015 LAUSANNE
Switzerland

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Region
Schweiz/Suisse/Svizzera Région lémanique Vaud
Activity type
Higher or Secondary Education Establishments
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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.

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