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Unravelling the molecular mechanisms of Type VI secretion system Pore-Forming Toxins

Objective

The T6S-PoreMech project aims to transform our understanding of bacterial warfare by analysing the Type VI secretion system's (T6SS) Pore-Forming Toxins (PFTs). It tackles two vital knowledge gaps: the absence of a systematic functional map of PFT families and the complete lack of atomic structures for their active, membrane-inserted pore form, representing a structural black hole.

The project proposes a new paradigm, suggesting that PFTs facilitate not just killing but also efficient predatory foraging through a controlled slow-bleed of nutrients from target cells. This vision will be evaluated through three integrated pillars.

1. Functional lexicon: Systematically identifying and characterising T6SS PFTs to differentiate between killing and foraging functions.

2. Atomic blueprint: Capturing the atomic structures of active PFT pores using advanced cryo-EM, overcoming technical challenges with innovative megabody technology.

3. Toxin-Immunity co-evolution: Unravelling the enigmatic mechanisms of PFT neutralisation by analysing toxin-immunity complex structures.

By connecting atomic structure to cellular function and ecological strategies, T6S-PoreMech will offer a revolutionary, multiscale perspective on microbial competition and establish a rational foundation for developing new antimicrobial therapies.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2025-ADG

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Host institution

FUNDACION BIOFISICA BIZKAIA / BIOFISIKA BIZKAIA FUNDAZIOA
Net EU contribution
€ 2 981 396,00
Address
BARRIO SARRIENA S/N
48940 Leioa
Spain
Region
Noreste País Vasco Bizkaia
Activity type
Research Organisations
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Total cost
No data

Beneficiaries (1)