Objective
The aim of this proposal is to identify the mechanism of Toll-like receptor 2 (TLR2) activation by bacterial lipopeptides (BLP) to initiate inflammation. Toll-like receptors (TLR) plays essential role in sensing microbial molecules or pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents. Recently, Dr. Zychlinsky's group identified that bacterial lipopeptides (BLP) are the activators of TLR2. BLPs are made by all prokaryotes and they signal through TLR2 for either the activation of the transcriptional activator NF-kB and for the induction of apoptosis. However, it remains unknown if this effect occurs via direct or indirect interaction of BLP with TLR2. In this study, we will test whether BLP binds directly to TLR2 by binding assays using soluble form of the recombinant TLR2 extra cellular domain in vitro. Synthetic BLP will be used in this study to rule out contaminants bearing others PAMPs motifs. If TLR2 binds directly to BLP, we will identify the BLP-binding motif from the extra cellular domain of TLR2 receptor by site directed mutagenesis. Induced apoptosis and cell activation will be evaluated in the transient mutant cell lines. On the other hand, if BLP fails to bind directly to TLR.2 we hypothesize, that
(1) BLP binds an adaptor protein in the membrane, or
(2) that BLP exhibits high affinity for lipid rafts, based on its acyl moiety. Acylation seems to be a required feature for raft targeting. This aim will be approached by UV cross-linked biotinylated-sBLP (PA-bioBLP) to THP-1 membranes followed by isolation and characterization of PA-bioBLP-containing raft. This approach will provide crucial information about the composition of the sBL/TLR2 signaling platform involved upstream of the TLR2 mediated signaling.
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 biomolecules proteins
- natural sciences biological sciences biochemistry biomolecules lipids
You need to log in or register to use this function
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.
Data not available
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.
Data not available
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
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
10117 BERLIN
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.