Direct measurements of RNA virus nucleocapsid self-assembly and disassembly

Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. This R35 MIRA proposal aims to measure and understand the molecular mechanisms of viral nucleocapsid self-assembly and disassembly through a combination of quantitative experimental methods, including two powerful single-particle methods: interferometric scattering (iSCAT) microscopy and cryo-electron microscopy (cryo-EM). We will apply these methods to a diverse set of RNA-packaging viruses with the goal of uncovering potentially universal mechanisms that span multiple virus types. Throughout, special focus will be paid to the role of RNA sequence and structure in directing these mechanisms. The results of this research could significantly enhance our fundamental understanding of nucleocapsid assembly and disassembly, two essential steps in the replication of all RNA-packaging viruses. Furthermore, the results could inform new classes of antiviral therapeutics that block these steps and halt the spread of pathogenic viruses, or they could inspire the design of next-generation delivery systems for genetic medicine. The project will also provide a technical roadmap for integrating iSCAT and cryo-EM, two highly powerful and highly complementary single particle microscopies, to address complex biological questions. In addition, the work will promote transdisciplinary training and career development for graduate and undergraduate students.