Phage-encoded host takeover: from molecular insight to biotechnological innovation

01/10/2026 to 30/09/2031

Antibiotic resistance is a growing global health threat. Bacteriophages represent a promising alternative through phage therapy, yet their full potential remains untapped due to limited understanding of how they hijack bacterial gene expression. A key challenge lies in the large proportion of uncharacterized phage genes – the phage “unknome” – and the poorly resolved architecture of phage transcriptomes, including non-coding RNAs. Our interdisciplinary research will integrate bioinformatics, machine learning, and experimental biology to systematically uncover phage-encoded mechanisms of RNA- and protein-based control of gene expression. In this project, we will (1) characterize host and phage transcriptome structures and uncover the functions of phage non-coding RNAs across diverse phage-host systems using RNA sequencing and genomic language models, and (2) functionally annotate the "phage unknome" using protein language models to identify novel host takeover mechanisms, focusing on phage-encoded ribosomal proteins. Subsequently, we will experimentally validate these mechanisms in E. coli-phage infections and study their potential for biotechnological applications. This research will offer new insights into phage biology and contribute to the development of innovative antimicrobial strategies.