Uncovering infection sensing in the molecular arms race between Bacteria and Bacteriophagescore
REDQUEEN · Horizon Europe grant · 2026-12-01–2031-11-30
EC contribution
Total cost
Beneficiaries
About the data
Source: CORDIS (official EU open data), Horizon Europe. Framework HORIZON · call ERC-2025-ADG · scheme HORIZON-ERC · topic ERC-2025-ADG. CORDIS record →
Objective
The phage-host arms race has been the ultimate breeding groThe phage-host arms race has been the ultimate breeding ground for ingenious evolutionary innovations in immunity and immune evasion such as CRISPR-Cas. Over 150 highly diverse phage defense systems have now been catalogued, yet fundamental mechanistic insights into how many of these innovations work at the molecular level - especially the sensing of infection - has remained a mystery. This knowledge gap constrains the use of these defense elements for further transformative applications in science and medicine, and limits fundamental insights into the relation between prokaryotic and eukaryotic innate immunity. In the timely project REDQUEEN, I ask the key question how bacteria sense phage invasion at different stages of infection, how they activate an antiviral response and what molecular innovations phage have evolved to counter infection sensing. I aim to capitalize on breakthrough discoveries and hypotheses from my group including DNA-sensing CRISPR-controlled transcriptional regulators, RNA-sensing multidomain nucleases, and phage-encoded broad inhibitors of defense involved in counter-sensing. Furthermore, I set out to create de novo designed proteins using artificial intelligence that can inhibit sensing and action of phage defense systems to create engineered phages able to overcome host defense. I will pursue my objectives through an integrated, interdisciplinary strategy that unites cutting-edge molecular microbiology, sequence and structure-based genomics with single-molecule biophysics and AI-driven protein design. This approach promises to uncover fundamentally new insights into the mechanisms of sensing and activation of viral immunity, while mining a rich genetic blackbox at the virus–host interface. By elucidating these processes, our work will inform strategies to modulate viral resistance and lay the groundwork for novel bacteriophage-based therapies against antibiotic-resistant pathogens.
Beneficiaries (1)
| Organisation | Country | Role | EC contribution | SME |
|---|---|---|---|---|
| TECHNISCHE UNIVERSITEIT DELFT | NL | coordinator | €2,500,000 |
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