Project description
Study of the newly discovered cyclic oligonucleotide-based bacterial immune system
All living things are prone to virus attacks, and cells have developed different immune systems to protect themselves, including the adaptive and innate immune systems of vertebrates and the CRISPR and restriction/modification systems of bacteria. Cyclic oligonucleotide-based antiphage signalling systems (CBASS) are a family of newly discovered bacterial immune systems, which generate an array of cyclic di- and tri-nucleotide signalling molecules that activate effector proteins to combat phage infection. The EU-funded CBASS project proposes a fundamental study of CBASS defence to identify new enzymes, pathways and mechanisms. The objective is to unveil the ways viral infection is detected by bacteria, the consequences for the cells, the role that protein modifications play and the ways the viruses overcome CBASS defence.
Objective
All living things are subject to attack by viruses. Cells have evolved many different immune systems to protect themselves, including the adaptive and innate immune systems of vertebrates and the CRISPR and restriction:modification systems of bacteria. Viruses have developed potent countermeasures to subvert these systems, and this perpetual arms race has been a strong driving force in evolution throughout the history of life on Earth. CBASS (cyclic-oligonucleotide-based antiphage signalling systems) is a newly discovered bacterial immune system with evolutionary links to the eukaryotic cGAS-STING innate immune pathway. CBASS generates an astonishing array of cyclic di- and tri-nucleotide signalling molecules that in turn activate a diverse range of effector proteins to combat phage infection. These cyclic nucleotide second messengers thus lead to life or death decisions for infected cells. CBASS are abundant in pathogens and the microbes that dominate the human digestive system: this microbiome and the viruses that infect it are now implicated in diverse aspects of human health. This is a powerful and complex defence system, but fundamental aspects are not understood. How is viral infection detected by bacteria, triggering cyclic nucleotide production? What are the consequences for the cell: does activation inevitably lead to cell death, or is there a mechanism to switch it off? What role does protein modification play? Furthermore, how do viruses overcome CBASS defence? These questions will be addressed using a cutting-edge combination of structural and molecular biology, bioinformatics, biochemistry and microbiology. We propose a ground-breaking study of CBASS defence, with a focus on discovery of new enzymes, pathways and mechanisms. This work will open up new paradigms in bacterial cell signalling with broad implications for our understanding of microbial physiology, infection and the evolution of immune systems.
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
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences cell biology
- medical and health sciences basic medicine physiology
- natural sciences biological sciences genetics nucleotides
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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)
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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.
ERC-ADG - Advanced Grant
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Call for proposal
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(opens in new window) ERC-2020-ADG
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KY16 9AJ ST ANDREWS
United Kingdom
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