Intellectual merit. Understanding the mechanics of virus budding is the focus of this research. This project employs state-of-the-art light microscopy to visualize the interactions of viral and cellular proteins that work together to facilitate the escape of mature viruses from mammalian cells. Many viruses, including the vesicular stomatitis virus (VSV), which is the subject of this research, and the better-known HIV, employ an escape strategy to exit cells once they have invaded and replicated themselves. This escape strategy requires the action of both viral and cellular proteins. Regular cellular proteins are redirected from their normal cellular locations and activities to the sites of virus budding. The exit process involves a large number of recruited cellular proteins and thus is complex, and while many of the key proteins have been identified, the manner and timing of their recruitment to the cell membrane and the interactions between them are only vaguely understood. Through recombinant virus technology and high-resolution live cell imaging, this project will investigate the timing and mechanisms of protein recruitment to the membrane thereby identifying rate-limiting steps and crucial interactions between proteins. The insights gained through this research promise to increase our basic understanding of the mechanisms involved in viral infection of cells.
Broader impacts. This project draws heavily from both biology and physics, two disciplines that have historically been separate but which blend together powerfully in the emerging study of cellular biophysics. Students will receive the important benefit of training in both biology and physics, allowing them to approach biological problems using rigorous quantitative analytical skills. This project embodies a strong commitment to the education of women and underrepresented groups. The project also involves outreach activities for both undergraduate and secondary school students, including in particular recruitment of high school and junior high school students from disadvantaged areas of Salt Lake City. This project emphasizes multi-disciplinary training and student opportunities, and possesses the potential to achieve important new insights into basic mechanics of virus replication.
