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Bacterial Amyloid Secretion: Structural Biology and Biotechnology.

Project description

Understanding the bacterial amyloid fibrils biogenesis system

Curli amyloid fibrils are a major functional component of the extracellular matrix in pellicle biofilms formed by Bacteroidetes and Proteobacteria. Curli formation requires a mechanistically unique biogenesis system. The ERC-funded BAS-SBBT project aims to study the structural and molecular biology of E. coli curli biosynthesis to uncover the fundamental molecular processes that allow the spatially and temporally controlled formation of the pro-amyloidogenic polypeptides. The objective is to unravel and analyse the secretion machinery for the subsequent in vitro reconstitution of a self-sufficient peptide transport and fibre assembly system. The ultimate goal is to develop a new framework to harness the properties of curli biosynthesis machinery for biotechnological applications in patterned functionalised nanowires and directed peptide carriers.

Objective

Curli are functional amyloid fibers that constitute the major protein component of the extracellular matrix in pellicle biofilms formed by Bacteroidetes and Proteobacteria. Unlike the protein misfolding and aggregation events seen in pathological amyloid diseases such as Alzheimer’s and Parkinson’s disease, curli are the product of a dedicated protein secretion machinery. Curli formation requires a specialised and mechanistically unique transporter in the bacterial outer membrane, as well as two soluble accessory proteins thought to facilitate the safe guidance of the curli subunits across the periplasm and to coordinate their self-assembly at cell surface.

In this interdisciplinary research program we will study the structural and molecular biology of E. coli curli biosynthesis and address the fundamental questions concerning the molecular processes that allow the spatially and temporally controlled transport and deposition of these pro-amyloidogenic polypeptides. We will structurally unravel the secretion machinery, trap and analyse critical secretion intermediates and through in vitro reconstitution, assemble a minimal, self-sufficient peptide transport and fiber assembly system.

The new insights gained will set the stage for targeted interventions in curli -mediated biofilm formation and this research project will develop a new framework to harness the unique properties found in curli structure and biosynthesis for biotechnological applications as in patterned functionalized nanowires and directed, selective peptide carriers.

Fields of science (EuroSciVoc)

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Topic(s)

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Funding Scheme

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ERC-COG - Consolidator Grant

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Call for proposal

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(opens in new window) ERC-2014-CoG

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Host institution

VIB VZW
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.

€ 1 989 488,75
Address
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgium

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Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Research Organisations
Links
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.

€ 1 989 488,75

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