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Quantifying minute forces: How mechanoregulation determines the behavior of pathogenic bacteria

Project description

Nanoscopic force measurements reveal how bacteria ‘flex their muscles’

In addition to electrical and chemical signalling, organisms and cells utilise mechanical inputs and outputs to perform their essential functions. In response to chemo-mechanical cues, bacteria generate traction forces that are critical to their ability to colonise surfaces, create biofilms and invade host cells. However, the pathways transducing input to outputs and even the actual inputs and outputs themselves are poorly understood, in large part due to the difficulty of measuring these minute forces in freely moving bacteria. The EU-funded BacForce project is developing pioneering methods to observe these forces. Experimental techniques combined with computer simulations will enable scientists to manipulate and characterise bacterial traction-force generation with important insights for biofilm formation and broad-sweeping application to nanoscopic force generation in cells.

Objective

Bacteria can generate mechanical forces that are important for the colonization of surfaces, formation of biofilms, and infection of host cells. This proposal addresses the fundamental question of how bacteria can control their force generation to robustly respond to chemo-mechanical cues on complex surfaces. Currently, a knowledge gap exists between the molecular regulation pathways on the one hand and the mechanical behavior on the other hand. One major impediment for understanding of how behavior is connected to control is, to date, the impossibility of studying bacterial force directly in unconstrained situations. Based on an initial study, I propose employing new methods for the unperturbed, high-resolution measurement of bacterial traction forces on wide spatiotemporal scales. Thus, the force-generation linking behavior to control can be investigated directly.
The objectives are to (A) gain access to nanoscopic mechanical phenomena through the development of cutting-edge super-resolution traction force microscopy, (B) employ the methods to characterize how Pseudomonas aeruginosa controls pilus-generated forces while responding to chemical cues, and (C) establish how surface rigidity affects force generation by P. aeruginosa during biofilm formation. In an interdisciplinary approach, I will combine traction measurements with genetic perturbations, molecule labeling, and computer simulations to produce functional models of the mechanocontrol strategies.
Altogether, I will establish a novel technique, opening up the possibility of studying nanoscopic force generation in many types of cells. Through these advances, I will characterize a set of mechanoregulation strategies in P. aeruginosa that are paradigmatic for diverse Gram-negative pathogens employing the same type of pili. Broadly, I expect that the studied bacterial control strategies have a generic, minimal nature and can appear as basic motives throughout development, homeostasis, and disease.

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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-2019-STG

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Host institution

TECHNISCHE UNIVERSITAT DORTMUND
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.

€ 381 250,00
Address
AUGUST SCHMIDT STRASSE 4
44227 Dortmund
Germany

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Region
Nordrhein-Westfalen Arnsberg Dortmund, Kreisfreie Stadt
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.

€ 381 250,00

Beneficiaries (2)

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