The work in my laboratory focuses on herpesviruses: ancient, ubiquitous viruses that infect most of the world’s population for life causing a panoply of ailments. We seek to answer several fundamental questions about the biology of these viruses. For example, why do they need an unusually large number of proteins to penetrate cells and how they do so? How do viral particles at different stages of disassembly or assembly traverse the crowded milieu of the cell and cross multiple intracellular membrane barriers? How are several dozens of components brought together to form mature, infectious particles set for the next round of successful cellular invasion? The resulting knowledge will not only illuminate the biology of these exceptionally complex viruses but inform new therapeutic approaches. We aim to answer these and other questions by employing a multidisciplinary approach that combines structural biology, virology, biophysics, and cell biology.
As Innovation Fund investigators, Ekaterina Heldwein and Daniela Nicastro are collaborating to investigate the assembly and trafficking of herpesviruses in host cells. For many viruses to complete the replication process, they must cross several host membrane barriers before exiting the cell. Herpesviruses in particular pass through the nuclear envelope barrier in a distinct manner that is different than other viruses, thus highlighting the potential for therapeutic intervention of this process. The pair will combine their expertise in virology, structural cell biology, and state-of-the-art imaging approaches to visualize how herpesviruses uniquely make their way through the nuclear envelope. This study will provide key structural insights into an essential step in the viral life cycle and expand the current knowledge of cellular membrane biology for preventing herpesvirus infections.