Elucidating molecular principles of RNA phage-host interaction

forthcoming

Bacterial viruses called phages are highly diverse predators with multifaceted life cycles. Recent major breakthroughs in phage biology brought phages back into the spotlight, highlighting their tremendous potential in basic and applied research. For instance, bacterial immune systems were shown to be the origin of human innate immune systems and there was significant progress in developing phages into therapeutics to treat multidrug-resistant bacterial infections. However, this recent renaissance of phage research neglected the study of phages with RNA genomes, which are a historically understudied group of phages with a fundamentally different biology from that of phages with DNA genomes. Consequently, the current developments in phage biology left the potential of RNA phages untapped. RNA phages rely on unique regulatory mechanisms during their replication cycles while requiring their hosts to employ specific immune systems to combat the infection. These unique phage and host mechanisms must be highly specific to guarantee efficient phage replication and avoid auto-immunity, respectively. I posit that understanding these processes is a prerequisite to utilize RNA phages as therapeutic agents and bears the potential to discover new biotechnological tools. In RIBO-PHAGE, I therefore aim to elucidate the unique lifestyle of RNA phages at the molecular level. Specifically, I will 1) Decipher how RNA phages regulate their replication for efficient propagation. 2) Elucidate the host factors RNA phages hijack during replication. 3) Determine how bacteria defend themselves against RNA phage infection. Building on my extensive background in RNA and phage biology, I will combine molecular biology and biochemistry methods with global high-throughput techniques using RNA phages of the Fiersviridae (e.g., MS2) and Cystoviridae (e.g., φ6) families as models. This project will provide a detailed picture of the molecular processes involved during RNA phage infection.