MIRACLe: Viewing Multi-segmented Viral RNA Assembly, Infection, and Evolution through the Biomolecular Condensate Lens

Rotaviruses are a diverse group of viruses responsible for >170,000 child deaths annually. This project seeks to deepen our understanding of the process by which multi-segmented RNA viruses, including rotaviruses, assemble their genomes. This will be achieved by focusing on three fundamental goals. Firstly, we intend to characterize the role that dynamic RNA structures play in the assembly of rotaviruses. We will decode the specific signals within the RNA that are responsible for selecting different segments, combining insights from experimental structural data and computational modeling. Lastly, we will explore the role of a process known as phase separation in the formation of structures we refer to as viral replication factories. By investigating these mechanisms in rotaviruses and related RNA viruses, we will reveal universal aspects of genome assembly in viruses with segmented genomes. Through these efforts, we will gain transformative insights into the replication cycle of multi-segmented RNA viruses by enhancing our understanding of how they leverage biomolecular condensates during replication, and how their individual RNA structures may shape their evolution. These findings will greatly enhance our knowledge of a large class of important pathogens, providing new avenues for the development of treatments and improved vaccines.