Project description
Molecular mechanisms of the Shango system
CRISPR-Cas systems have advanced genome editing, while bacteria use over 130 gene modules as defence mechanisms against phages. The Shango system, a bacterial anti-phage defence module, consists of three core genes (SngA, SngB, and SngC) which likely contribute to DNA remodelling. Supported by the Marie Skłodowska-Curie Actions programme, the SHARP project will investigate the molecular mechanisms of the Shango system by isolating phage variants that evade its defence. The project aims to identify triggering signals. Using advanced techniques such as cryogenic electron microscopy (cryo-EM) and total internal reflection fluorescence microscopy, it will examine Shango’s functional states, with the goal of visualising the co-localisation of Shango proteins and phages during attacks.
Objective
The SHARP (Shango Anti-phage Remodeling Pathway) project aims to explore the molecular mechanism of Shango system, a widespread bacterial anti-phage defense module. While the well-known CRISPR-Cas systems have revolutionized genome editing, bacterial defense strategies encompass over 130 distinct gene modules and present a treasure chest for novel biotechnologies. To eliminate viral threats, these systems employ various mechanisms, either pre- or post-injection. Shango consists of three core genes: SngA, SngB, and SngC with bioinformatically predicted functions thus far. SngA, annotated as tellurite stress response element, has two transmembrane helices and is proposed to detect an unknown viral signal. Its C-terminal domain may recruit SngB and SngC. SngB, a member of the AAA+ ATPase family, together with SngC, a DEAD-box helicase, likely participates in DNA remodeling.
In this project, I hypothesize that Shango induces changes in nucleic acid topology, thus impairing phage genome integrity and preventing its replication, though the exact mechanism remains elusive. By isolating phage escapers capable of bypassing Shango, I aim to identify the triggering signal. Subsequently, I will analyze the specificity and unwinding activity of SngB and SngC using biochemical assays. Advanced techniques such as single-particle cryogenic electron microscopy (cryo-EM) will be used to elucidate distinct functional states of Shango. Leveraging Dr. N. Taylor’s expertise, I aim to assemble the complete complex of Shango together with its transmembrane helices. To reveal the spatial-temporal regulation of the system during phage attack, I will employ Total Internal Reflection Fluorescence (TIRF) microscopy to visualize the co-localization of Shango proteins and phages. This project not only explores new aspects of bacterial stress responses, but also aims to pioneer tools for signal-induced nucleic acid manipulations, opening up the possibilities in biotechnological applications.
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 biochemistry biomolecules nucleic acids
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy electron microscopy
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2024-PF-01
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1165 KOBENHAVN
Denmark
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