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 componentsThe focus is the complex role miRNAs are playing in innate immunity and inflammation. Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-LS6 - ERC Advanced Grant - Immunity and infection Call for proposal ERC-2010-AdG_20100317 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Coordinator THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD, OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN Address College green trinity college D02 CX56 Dublin 2 Ireland See on map Region Ireland Eastern and Midland Dublin Activity type Higher or Secondary Education Establishments Administrative Contact Deirdre Savage (Ms.) Principal investigator Luke O'neill (Prof.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD, OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN Ireland EU contribution € 2 480 586,80 Address College green trinity college D02 CX56 Dublin 2 See on map Region Ireland Eastern and Midland Dublin Activity type Higher or Secondary Education Establishments Administrative Contact Deirdre Savage (Ms.) Principal investigator Luke O'neill (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
