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Reconstructing the coordinated self-assembly of a bacterial nanomachine

Project description

A tale of a tail: understanding self-assembly of multiple proteins into functional nanomachines

Bacteria move around using flagella, propeller-like appendages that allow directed movement towards nutrients, other attractants and preferred sites of infection. About 20 nm in diameter, the flagellar filament is rotated by a motor located in the cell envelope. The entire flagellum is a complicated nanomachine in which multiple proteins form the rings that anchor the flagellum in the membrane, act as the motor and form the filament itself. While other studies have focussed on genetics and the characterisation of subcomponents, the EU-funded BacNanoMachine project plans to enhance our understanding of the coordinated self-assembly of all the building blocks in bacteria in time and space. It will advance our basic understanding of these processes and potentially also have implications for the rational design of novel antibiotics and for synthetic molecular machines for a variety of applications.

Objective

Life has evolved diverse protein machines and bacteria provide many fascinating examples. Despite being unicellular organisms of relatively small size, bacteria produce sophisticated nanomachines with a high degree of self-organization. The motility organelle of bacteria, the flagellum, is a prime example of complex bacterial nanomachines. Flagella are by far the most prominent extracellular structures known in bacteria and made through self-assembly of several dozen different kinds of proteins and thus represents an ideal model system to study sub-cellular compartmentalization and self-organization. The flagellum can function as a macromolecular motility machine only if its many building blocks assemble in a coordinated manner. However, previous studies have focused on phenotypic and genetic analyses, or the characterization of isolated sub-components. Crucially, how bacteria orchestrate the many different cellular processes in time and space in order to construct a functional motility organelle remains enigmatic. The present proposal constitutes a comprehensive research program with the aim to obtain a holistic understanding of the underlying principles that allow bacteria to control and coordinate the simultaneous self-assembly processes of several multi-component nanomachines within a single cell. Towards this goal, we will combine for the first time the visualization of the dynamic self-assembly of individual flagella with quantitative single-cell gene expression analyses, re-engineering of the genetic network and biophysical modeling in order to develop a biophysical model of flagella self-assembly. This novel, integrative approach will allow us to move beyond the classical, descriptive characterization of protein complexes towards an engineering-type understanding of the extraordinarily robust and coordinated assembly of a multi-component molecular machine.

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Keywords

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Programme(s)

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Topic(s)

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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

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(opens in new window) ERC-2019-COG

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Host institution

HUMBOLDT-UNIVERSITAET ZU BERLIN
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.

€ 1 934 950,00
Address
UNTER DEN LINDEN 6
10117 Berlin
Germany

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Region
Berlin Berlin Berlin
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.

€ 1 934 950,00

Beneficiaries (1)

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