PHAGECOUNTER · Discovery of counter defense strategies of bacteriophages against bacterial immunity

Tight co-evolutionary interactions of bacteria and their viruses, termed bacteriophages or phages, lead to continuous selection towards adaptation of the host and counter-adaptations of the parasite. Studying this evolutionary arms race resulted in discovering multiple sophisticated defense mechanisms of bacteria, such as CRISPR-Cas and restriction-modification systems. However, the diversity and mechanisms of action of counter-defense strategies of phages remain largely unknown. In this proposal, I will address this problem.The pan-genome of the phages is proposed to encode for proteins with counter-defense function. I will test this hypothesis using the largest, fully genome sequenced virus-host interaction network to date treasured in the host lab. I will combine comparative population genomics with computational biology, classical molecular genetics, transcriptomics, and proteomics. This approach will allow me to address my research objectives: (1) to identify counter-defense proteins of the phages, (2) validate the counter-defense properties, and (3) determine at which stage of phage infection the counter-defense occurs.This research will allow me to elucidate the diversity of previously unknown counter defense strategies of phages and expand our knowledge of their mechanism of action. Importantly, my approach shifts the paradigm of studying bacterial defense systems and the escape mechanism of phages and will open up many novel avenues in bacterial immunity and microbial population genomics. Implementation of the proposed project will enhance my proficiency by improving and diversifying my experimental and computational science skills and boosting my transferable skills, such as scientific communication and writing, project management, and networking. This altogether will improve my competitiveness and potential on the way to an independent career. Thus, the proposal corresponds well with the aims of the Work Programme.