RESIST Guest Group Quantitative and Molecular Virology

Herpesviruses assemble in a complex order of consecutive and convoluted morphogenesis events that involve large macromolecular complexes interacting with host-derived membranes. Advances in structural methods allow us now to characterize these transitional states in-situ. Unfortunately, the kinetics and dynamics of these processes often remain unstudied because purification for classical biochemistry usually disables the superstructures and ensemble assays lack resolution. For these reasons, very little is known about the in-situ dynamics and kinetics of herpesvirus assembly intermediates at single-particle resolution. This information is, however, crucial to mechanistically understand the effect of pharmacological inhibitors on virus productivity.

To fill this gap, the group Quantitative and Molecular Virology at the MHH & the CSSB develops functional assays to quantify and mechanistically describe the kinetics and dynamics of viral macromolecular complexes in living cells at the single particle level. To this end, we use light microscopy with very high spatiotemporal resolution and develop novel imaging modalities. In addition, we create computational pipelines to analyze large image datasets.

Currently, we are working on the question of how capsid-membrane association and dissociation is regulated. To this end, we cooperate closely with our colleagues at the LIV as well as with our international Wellcome Trust Collaborators by integrating our kinetic models into multimodal frameworks of virus morphogenesis. The close association of this research team with the LIV's microscopy core also allows us to drive technology development along biological questions.