Objective
MicroRNAs (miRNAs) are important regulators of both innate and adaptive immunity. This is very much a frontier area since little is known about miRNA function in vivo, and there is still much discovery to be done. Their emerging functions indicate that they are as potent as cytokines in immunoregulation.
We have found that Toll-like receptor (TLR) signaling is potently modulated by 2 particular miRNAs, miR-21 and miR-107. The programme will have 4 aspects which will build on this initial observation.
1. Extension of our observations on miR-21 and TLR signaling. We found that the translational repressor PDCD4 is a key target. We will study miR-21-deficient mice, construct a mouse model where the miR-21 seed sequence in the 3'UTR of PDCD4 is altered, and target miR-21 in vivo using antagomirs. We will also determine the mRNAs regulated by PDCD4 and examine the role of mTOR in PDCD4 control since PDCD4 is a possible substrate.
2. Examination of the role of miR-107 in TLR signaling. TLRs dramatically decrease it¿s expression. We have found that miR-107 has an inhibitory role in TNF secretion via the targeting of CDK6. Activation of PPAR-alpha increases expression of miR107, which could be part of the anti-inflammatory effect of PPAR-alpha ligands. We will explore miR-107-deficient mice and in vitro models of miR-107 function.
3. Exploring the targeting of miR-155 by IL10, which we have recently found. The miR-155 target SHIP1 may be important in this system. We will analyze this process in detail and determine other targets for miR-155 in IL10 action.
4. Perform a screen for novel regulators of the aforementioned miRNAs and screen for miRNAs as regulators of other innate immune pathways, including Nalp3 and RIG-I, about which little is known. These experiments will yield new insights and components
The focus is the complex role miRNAs are playing in innate immunity and inflammation.
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.
ERC-2010-AdG_20100317
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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.
Host institution
D02 CX56 Dublin
Ireland
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.