Objective
MicroRNAs (miRNAs) can be transferred between cells, representing an exciting new dimension to intercellular communication, referred to as non-cell-autonomous gene regulation. We recently identified that distinct miRNAs are packaged and exported from TREG cells and delivered directly to TH1 cells, suppressing T cell-mediated disease. Different T cell populations express different miRNAs and release a distinctive set of extracellular miRNAs. In this proposal we will identify whether the transfer of miRNAs between cells contributes to T cell development, T cell differentiation and TH2-mediated allergy and anti-helminth immunity. miRNA-mediated gene silencing requires one of four catalytically active Argonaut (Ago) proteins to regulate gene expression. To investigate miRNA transport between cells, we have generated novel mice with miRNA-deficient T cells that can (Dicer–/–) or cannot (Dicer–/–Ago-1,-3,-4–/– Ago-2fl/fl) respond to exogenous miRNAs. Using these novel mice we will identify which Ago protein(s) specific miRNAs associate with and which Ago proteins are required for miRNA-mediated gene regulation in T cells. TH2 cells express unique miRNAs, which can be found within TH2 cells and in extracellular vesicles released from TH2 cells. We have generated several new TH2-associated miRNA-deficient mice to investigate the cell intrinsic (cell-autonomous) and extrinsic (non-cell-autonomous) role of these miRNAs in TH2-mediated allergy and anti-helminth immunity. Studies in plants and worms have identified various mechanisms of RNA transfer between cells, involving cell-contact dependent and independent mechanisms. We will translate these observations into mammalian systems and identify the mechanisms of miRNA transfer. Results from this work will identify novel miRNA-mediated pathways and incentivise state-of-the-art approaches for novel therapeutic intervention to treat inflammatory diseases.
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.
- medical and health sciences health sciences inflammatory diseases
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences cell biology
- medical and health sciences clinical medicine allergology
- natural sciences biological sciences genetics RNA
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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.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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.
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.
ERC-COG - Consolidator Grant
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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.
(opens in new window) ERC-2014-CoG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
NW1 1AT London
United Kingdom
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.