Project description
Identifying novel cyclic nucleotide signalling in humans
Cell survival depends on processing environmental information, primarily through second messengers like cyclic nucleotides (CNs). CNs are diverse and significant in bacteria and humans, and show promise in cancer immunotherapy. However, many human nucleotidyltransferases (NTases) remain uncharacterised in the absence of their ligands. The ERC-funded NTasePro project will uncover the molecular functions of uncharacterised NTases and identify novel CN signalling pathways in humans, focusing on both immune and non-immune contexts. It will activate these NTases and explore their roles in immune responses. This approach suggests that uncharacterised CNs are critical for immune signalling and other pathways. Results could reveal new biological regulation mechanisms and pave the way for new therapeutic options using CNs as drugs.
Objective
Survival of a cell depends on its ability to receive and process information coming from the environment. Second messengers are the key transmitters of information that rapidly amplify the signal inside the cell. Cyclic nucleotides (CNs) are the most diversified category of second messengers and are found in all organisms modulating diverse pathways. CNs are best studied in bacteria, where they have a variety of biological functions. In humans, the only described cyclic di-nucleotide is cGAMP, which elicits an antiviral immune response. cGAMP is rapidly emerging as a promising drug candidate in e.g. cancer immunotherapy. I hypothesise that additional CNs contribute to yet uncharacterized pathways in humans and my aim is to discover novel CNs and their signalling pathways. CNs are synthesized by nucleotidyltransferases (NTases) and many human NTases remain uncharacterized by the lack of activity in the absence of the cognate ligand.
This project aims to reveal the molecular function of uncharacterized NTases and to discover novel CN signalling pathways in humans in immune and non-immune-related areas of biology. I will focus in Objective on the activation of as yet uncharacterized NTases and in Objective I want to identify CN signalling pathways involved in immune responses and beyond. The proposed experiments will provide me with candidates and precedence for CN signalling in humans other than cGAMP. The concept that yet uncharacterized CNs are involved in immune signalling as well as other pathways is highly innovative. Together, the well-studied activities in bacteria and the overall conservation of NTases in humans, further support fundamental involvement of CN signalling in humans. My proposed research will open up conceptually new modes of regulation in human biology, reveal novel signalling pathways and in the long-term contribute to new therapeutic options using CNs as drugs.
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 clinical medicine oncology
- natural sciences biological sciences genetics nucleotides
- medical and health sciences basic medicine immunology immunotherapy
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antivirals
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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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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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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.
Funding Scheme
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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-2023-STG
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80333 Muenchen
Germany
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