MICHAEL, BAUER Name of your research group: Müller Department/Institute Institute of Molecular Cancer Research (IMCR) Street, Post Code City Winterthurerstrasse 190 8057 Zürich Email: bauer@imcr.uzh.ch Link to your website https://www.imcr.uzh.ch/en/research/Muller/Team/Bauer.html

KEYWORDS – BACTERIAL INFECTION, H. PYLORI, TIFA/ALPK1 SIGNALLING, DNA DAMAGE, R-LOOPS MAIN FIELDS OF RESEARCH; ABSTRACT The gastric pathogen Helicobacter pylori is best known for its carcinogenic properties and link to gastric malignancies. We are interested in the mechanisms underlying gastric carcinogenesis, which we study in cell culture systems and mouse infection models. We believe that H. pylori promotes gastric (pre-) malignant transformation through at least two processes. On the one hand, exposure to live bacteria severely compromises the stability of the host genome. We find evidence of genomic instability in all eukaryotic cells that have been exposed in vitro to wild type H. pylori strains; manifestations of genomic instability include strand discontinuities as evidenced by microscopy of metaphase chromosomes, fragmented DNA detected by pulsed-field gel electrophoresis, and the recruitment of repair factors to sites of DNA damage (Toller et al., PNAS 2011). A genome-wide screen for H. pylori factors involved in DNA damage implicated the Cag pathogenicity island-encoded type IV secretion system and the activation of NF-kB-dependent transcription triggered by this system (Hartung et al. Cell Reports 2015). We have more recently discovered that R-loop formation at sites where the transcription and replication machineries collide in actively proliferating cells gives rise to DNA double strand breaks (DSBs) (Bauer et al., in preparation). Further we were able to identify the bacterial LPS-intermediate β-ADP-heptose inducing R-loops and DSBs in an ALPK1/TIFA-signaling manner. Moreover we could show that the DNA damage arising in H. pylori infection is restricted to S-phase cells. SPECIAL TECHNIQUES AND EQUIPMENT PULSED FIELD GEL ELECTROPHORESIS (PFGE), Immuno-fluorescence microscopy, Western Blot, DNA-fiber assay, In viro/vivo infection, ELISA, FACS sorting, q-PCR,