Objective
Shigella invades the intestinal epithelium following injection of type III secretion effectors (T3S) and causes inflammatory, neutrophil-mediated tissue destruction. The host lab has shown that Shigella invasion induces oscillatory Ca2+-signalling and hemichannel-dependent release of ATP, which is a potent immunostimulatory signal. I propose 1) that ATP release from epithelial cells attracts neutrophils to sites of infection and promotes their activation and 2) that some Shigella T3S effectors counter these effects during early stages of infection, to escape neutrophil-mediated killing. I will focus on the effector IpgD. I will determine the ability of IpgD to dampen hemichannel opening during Shigella invasion of epithelial cells. By means of 4D live imaging, I will correlate neutrophil migration with wild-type and ipgD mutant Shigella invasion of epithelial cells and formation of ATP gradients. Also, I will test immune functions of neutrophils exposed to extracellular ATP during wild-type and ipgD mutant Shigella invasion. Further, using a transwell chemotaxis assay and 4D live imaging, I will investigate IpgD-mediated inhibition of cytoskeletal dynamics, i.e. migration, in neutrophils. My work will assess the physiological significance of ATP release during Shigella invasion and contribute to define T3S effectors functions other than invasion, i.e. immunomodulation. This may allow to design new therapeutic approaches. Live imaging, work with live pathogens and primary immune cell cultures are new techniques for me. Together with the expertise acquired previously, the training I will receive in the lab of Prof. Philippe Sansonetti will be integral to my carrier studying host-pathogen interaction.
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 chemical sciences inorganic chemistry alkaline earth metals
- medical and health sciences basic medicine immunology
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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.
FP7-PEOPLE-2007-2-1-IEF
See other projects for this call
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.
Coordinator
75724 Paris
France
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.