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Multi-scale model of bacterial cell-cell interactions

Objective

Transporting selected proteins across the cell envelope in a controlled manner is a fundamental property of all cell types. For bacteria, secretion systems play a central role in the translocation of effectors that mediate interactions with other cells. The bacterial Type VI Secretion (T6S) system is one of the most widespread secretion systems and, in a cell-cell contact-dependent fashion, it injects effectors into eukaryotic and bacterial targets. The T6S system utilizes a cytoplasmic phage tail-like apparatus that is anchored to the cell envelope. A contractile sheath propels a macromolecular effector-loaded tube/spike-complex outside the cell and into the target.

Here, we will establish a model of T6S-mediated cell-cell interactions by integrating information from the molecular, cellular and intercellular scales. The model will reveal answers to three paramount questions of the field: Aim 1 (molecular scale) will elucidate an atomic model of the T6S membrane-anchoring complex in loaded and fired conformational states. Aim 2 (cellular scale) will identify the mechanisms and relevance of clustering multiple T6S machines in a confined region of the cell. Aim 3 (intercellular scale) will resolve T6S actively engaged in cell-cell interactions to clarify the in vivo structure and significance of the inner tube in effector translocation and target cell penetration.

Electron cryo-tomography (ECT) will be used as the key technique to resolve unique structures in their cellular context, in a native state, in three dimensions and at the crucial nanometer-to-micrometer range. Cryo-focused ion beam milling will be established to prepare samples thin enough for ECT imaging. ECT data will be complemented by high-resolution structural information of sub-complexes (in vitro) and low-resolution fluorescence light microscopy data on dynamics (in vivo). In the future, our approach will prove useful to study other types of bacterial cell-cell interactions.

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Topic(s)

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Funding Scheme

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2015-STG

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Host institution

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
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.

€ 1 751 853,00
Address
Raemistrasse 101
8092 Zuerich
Switzerland

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Region
Schweiz/Suisse/Svizzera Zürich Zürich
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.

€ 1 751 853,00

Beneficiaries (1)

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