Objective
The antimicrobial resistance crisis is escalating, and while phage therapy can clear acute infections, eradication of chronic infections reThe antimicrobial resistance crisis is escalating, and while phage therapy can clear acute infections, eradication of chronic infections remains elusive. This limitation is attributed to host physiology under stress that limits phage replication. But the prevailing assumption that virulent phages inevitably proceed to lysis is increasingly challenged. Our recent findings show that nucleus-forming phages can replicate in synchrony with their host across generations without lysis—a phenomenon we summarize as permanent phage replication cycle. This replication strategy is invisible to classical plaque assays, mechanistically unexplored, and may explain why chronic infections resist clearance.
Hypothesis. Nucleus-forming phages use their specialised compartments together with host-takeover factors to establish and maintain permanent replication under stress. If we can define, measure, and disrupt this cycle, we can convert persistence into clearance.
Aims. Define and quantify permanent replication cycles. Map the molecular landscape of permanency. Identify and characterize key determinants, and engineer phages that bypass permanency to generate hyper-virulent phages.
Approach. We combine quantitative virology, utilise time-resolved single-cell assays and fluorescence imaging and electron microscopy in a validated E. coli–Goslarvirus model that demonstrates both technical feasibility and a clear knowledge gap.
Impact. The project will (i) deliver the first mechanistic framework for the permanent phage replication cycle, (ii) establish tools and criteria to detect permanency, guiding the discovery of novel phages, and (iii) provide a rational framework for designing therapeutic phages that skip permanency—enabling faster clearance. This work reframes virulent phage biology and lays the foundation for next-generation phage therapy.
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Keywords
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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.
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-2026-STG
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38124 Braunschweig
Germany
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