séminaire CIRI : Alexander Harms (09.03.2026)

Alexander Harms, Assistant professor at the department of health sciences and technology, ETH Zürich, "Shining light on the dark matter of viral genomes".

Abstract: The billion-year arms race between bacteriophages and their bacterial hosts has inspired molecular microbiology since its first golden era almost a century ago. However, most fundamental research has focused on a handful of model phages, leaving the enormous diversity of phage biology underexplored. We therefore assembled the BASEL collection as a reference set representing all major viral groups infecting Escherichia coli. To unlock previously inaccessible viral groups, we have engineered the E. coli K-12 laboratory strain to overcome inherent limitations such as its lack of O-antigen glycans and multiple layers of bacterial immunity. In parallel, we developed HIDEN-SEQ as the first transposon-insertion sequencing approach for bacteriophages. HIDEN-SEQ can systematically link genes from the abundant “dark matter” of phage genomes to any selectable phenotype. Across diverse phages, hosts, and growth conditions, HIDEN-SEQ delivers near-base-pair-resolution maps of viral gene essentiality. As an example, we used HIDEN-SEQ to discover previously unknown anti-defense genes that enable phages to infect different E. coli strains and then matched them to specific antiviral defense systems of those hosts. Taken together, this work widely expands the scope of viral functional genomics and will enable major advances from fundamental research to applications in clinics and biotechnology.