Will Wan, Ph.D.
Assistant Professor, Biochemistry
Member, Vanderbilt Center for Structural Biology
Viral life cycles of negative-sense RNA viruses
Research Keywords: Structural virology, Ebola virus, rabies virus, cryo-electron tomography, in situ structural biology.
Research Description: The Wan lab is interested in studying the molecular interactions that drive viral life cycles. This includes studying the structure of intact viral particles as well as characterizing how viral molecules interact with host molecules in infected cells. Our lab is focused on members of the viral order Mononegavirales, which contains a wide range of important human pathogens that share a common negative-sense single-stranded RNA genome. Despite their evolutionary relationship, Mononegaviruses infect a wide range of hosts with each viral species exhibiting distinct cellular and molecular pathologies. Our main viral systems are Ebola, measles, and rabies viruses, which represent emerging, re-emerging, and neglected infectious diseases, respectively.
Current projects in the lab include:
- Determining the molecular architecture of pleomorphic viruses.
- Characterizing the host-pathogen interactions that drive Ebola virus assembly.
- Understanding how viral infection drives changes in host cell biochemistry.
- Studying the molecular pathology of rabies infection in neurons.
Our lab uses a range of different approaches including viral reverse-genetics as model systems for high-biosafety level viruses, live cell fluorescence microscopy to monitor cellular changes during viral infection, and cryo-electron tomography for molecular-resolution imaging of near-native specimens.
Significance: Mononegaviruses include a number of important human pathogens that have distinct viral life cycles. Current approaches to treating these viruses include vaccines or antibody therapeutics, both of which target the viral glycoproteins, making such approaches susceptible to a single point of failure. Furthermore, such therapeutics can often be difficult to provide to the communities most affected by these diseases. By studying how viral molecules interact with host cells to drive viral pathogenesis, we will obtain a more holistic understanding of their viral life cycles. Studying prototypical members of different mononegavirus families will further provide insights into how evolutionarily-related molecules can drive different cellular pathologies. A holistic approach of understanding host-virus interactions is an essential step towards developing novel classes of therapeutics with wider ranges of molecular targets.