Objective
RNA lies at the core of the central dogma of molecular biology. It can both store genetic information and catalyse biochemical reactions. An often-overlooked property is that it contains next to A, G, C, and U, approximately 170 different non-canonical nucleosides. Transfer RNAs (tRNAs), as the central adaptor molecules for translating, harbour the highest number of these non-canonical nucleosides.
A recent surprising discovery revealed that tRNAs are cleaved by, in part, unknown RNases into smaller fragments, referred to as tsRNAs, which keep the non-canonical nucleosides. The functions of this entirely novel class of RNA molecules remain unknown.
Our first goal is to prepare phosphoramidite building blocks for non-canonical nucleosides and to synthesize tsRNAs. Although all available knowledge about tsRNAs has been obtained using synthetic RNAs that lack modified nucleosides, the data suggest that their primary function is to stimulate the immune system to enhance for example anticancer responses. Consequently, we plan to focus our synthetic efforts at evaluating the immunological effects of tsRNAs. This aim is further supported by the seminal discovery of Weissman and Kariko, who demonstrated that the presence of non-canonical nucleosides, such as pseudouridine, in mRNA profoundly modulates immune recognition.
The second goal of the study is to employ the synthetic tsRNAs, containing the respective embedded non-canonical nucleosides, to investigate how these fragments are processed by specific RNases. We will analyse how tsRNAs, or their secondary cleavage products, activate immune responses. Furthermore, we plan to identify and characterize the enzymes involved in these processing pathways. Finally, we will study tsRNAs derived from pathogenic bacteria following infection, focusing on those carrying pathogen-specific non-canonical nucleosides. We hypothesize that these structures will elicit particularly strong immune responses.
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 microbiology bacteriology
- medical and health sciences basic medicine immunology
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences biological sciences molecular biology
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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)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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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.
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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.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-ADG
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80539 Planegg
Germany
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