Objective
Type-III secretion (T3S) systems allow Gram-negative pathogenic bacteria to reprogram eukaryotic host cells by injecting effector proteins through a eukaryotic membrane into their cytosol. Salmonella enterica are facultative intracellular enteropathogens t hat infect humans and animals, causing a wide range of diseases.
Salmonella reside and replicate inside host cells in a membrane-bound compartments called Salmonella-containing vacuoles (SCVs), which use a unique trafficking pathway. The Salmonella pathogenicity island-2 (SPI-2) T3S system is required for intracellular bacterial replication. This indicates that SPI-2 effectors, delivered through the vacuolar membrane, act on intracellular trafficking to mediate the creation of a niche permissive for bacteri al multiplication.
The SCVs acidifies to between pH 4.0-5.0 and in vitro SPI-2-mediated T3S is triggered by this pH range. This suggests that acidic pH might be the physiological stimulus for SPI-2-mediated T3S inside the SCV. In this project, we aim to characterize SPI-2 T3S triggering, understand its role in Salmonella pathogenesis, and gain deeper insights on the mechanisms employed by pathogens to modulate intracellular trafficking.
We propose to screen and characterize the gene(s) required for in vitro SPI-2 T3S triggering; investigate the mode of action of the affected protein(s); determine if acidification triggers T3S inside the SCV; and study the influence of vacuolar pH on Salmonella intracellular trafficking and multiplication. We will use a wide genome screening method to study the mechanisms of virulence of a very important human and animal pathogen.
The full understanding of the SPI-2 T3S triggering will open the possibility of developing specific drugs to combat Salmonella infections. Thus, this project fits within the objectives of the 6th Framework Programme, in the category life science, genomic and biotechnology for health.
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.
- medical and health sciences health sciences public health
- medical and health sciences health sciences infectious diseases
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- medical and health sciences basic medicine physiology homeostasis
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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.
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.
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.
FP6-2004-MOBILITY-5
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Funding Scheme
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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.
Coordinator
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.