Objective
Intestinal epithelial cells (IECs) constitute the primary barrier that enteric pathogens have to face. The mechanism by which innate immunity is regulated in IECs remains unclear. However, it is known that a delicate balance is required to efficiently recognize pathogens and at the same time to not illicit an immune response against the commensal microbial flora. Inappropriate immune response to the commensal flora is suspected to be responsible for inflammatory bowel diseases.
We found that IECs could generate a different innate immune response upon viral infection, depending on where the infection originates from (apical vs. basolateral). Moreover, infection of the cells from the apical plasma membrane (gut lumen) renders IECs less responsive to subsequent viral infection. This down-regulation of innate immune response could represent a mechanism developed by IECs to avoid recognition of the commensal flora thereby preventing constant inflammation of the bowel.
The objective of this project is to discover the means by which antiviral innate immunity is achieved and regulated in IECs. We will use a multidisciplinary approach, combining live-cell microscopy, single particle/molecule tracking, biochemistry, and genomics. The specific aims are:
1) Determine the importance of RLR and TLR in generating an innate immune response in IECs
We will characterize the signaling pathways triggered upon viral infection of IECs from the apical and basolateral sides. We will characterize the mechanism by which apical infection downregulates the innate immune response of subsequent infection.
2) Spatio-temporal aspect of viral RNA recognition in IECs
We will develop new tools to study, within a living cell, the spatio-temporal aspect of virus detection by the cellular sensors RLR and TLR. We will determine how signal transduction is initiated or orchestrated upon detection of infection. We will address whether recognition of the pathogen and signal transduction takes place in different sub-cellular compartments depending on the site of virus entry (apical vs basolateral).
3) Impact of cellular polarization on signal transduction during innate immune response
We will characterize the signal transduction pathways of various TLR in polarized IECs and oppose it to the signaling pathways generated by non-polarized IECs. We will determine the location (plasma membrane or endosomal compartment) from where TLRs signal from in polarized IECs and oppose it to non-polarized cells. We will identify and characterize the molecular mechanisms that allow IECs to remodel TLR signaling upon cellular polarization. Ultimately, we will determine the reasons for such TLR signaling remodeling.
The long-term goal of the laboratory is to understand how IECs can tolerate the commensal flora (bacteria and viruses) and at the same time efficiently recognize enteric pathogens.
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 biochemistry
- natural sciences biological sciences microbiology virology
- medical and health sciences clinical medicine gastroenterology inflammatory bowel disease
- medical and health sciences basic medicine immunology
- natural sciences biological sciences genetics RNA
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
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-2012-CIG
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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
69120 HEIDELBERG
Germany
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.