Project description
Bacteria under pressure: finding their breaking point could point to new therapies
Cellular signal transduction is not subserved only by chemicals such as hormones in the bloodstream or electrical currents as in the nervous system. Mechanotransduction, the conversion of mechanical forces into biochemical signals, plays a vital role in controlling cellular functions including proliferation, differentiation and migration. This process has primarily been studied in eukaryotic cells, whereas the role of mechanotransduction in bacteria is still poorly understood. Harnessing this pathway could enable new targets for therapies. With the support of the Marie Skłodowska-Curie Actions programme, the NIOBMT project is investigating the mechanical stability of a common human pathogen on the trail of ways to disrupt its mechanotransduction pathway.
Objective
Mechanical force is a ubiquitous perturbation that operates at all levels of life, from single molecules to organs. At the tissue level, cells are constantly exposed to forces exerted by their surrounding environment—body fluids, neighboring cells, or the extracellular matrix. The process by which cells sense and convert physical stimuli into a biochemical signal is known as mechanotransduction. When mechanical forces reach the nucleus, they can activate several force-induced transcriptional pathways that control cell functionality. The failure of these pathways has been linked to several human pathologies, such as cancer. While most of our knowledge in mechanobiology is focused on mammalian cells, comparatively little is known on how prokaryotes detect, interpret, and generate a response to physical inputs. Understanding how bacteria sense mechanical forces and how these signals are integrated to promote colonization, biofilm formation, or virulence development is crucial to develop therapeutic strategies that target the pathogenesis onset. Here we propose a cross-scale approach that first employs single-molecule force spectroscopy techniques to study in vitro the dynamics under force of PilY1 —from the Gram-negative opportunistic pathogen Pseudomonas aeruginosa— and how antibody binding affects its mechanical stability. Our goal is to implement a molecular-based strategy that disrupts the PilY-triggered mechanotransduction pathway, which we will probe at the cellular level. Using a combination of optical microscopy and single-cell mechanical techniques, we will monitor in vivo the downstream events that lead to the expression of genes that promote virulence after PilY1 mechanical stimulation in the absence and presence of antibodies that disrupt the activity of this protein.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences cell biology cell signaling
- natural sciences biological sciences microbiology bacteriology
- natural sciences physical sciences optics spectroscopy
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2020
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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.
WC2R 2LS London
United Kingdom
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.