Daniel Wrapp

Many of the proteins that viruses use to infect host cells exist in a “metastable” state, allowing them to rapidly undergo dramatic conformational changes when they encounter conditions that are permissive for infection. These conformational changes are critical to the viral lifecycle, making some of these viral proteins ideal targets for the development of vaccines or other therapeutic interventions. Unfortunately, the inherent metastability of these proteins makes their expression and purification notoriously difficult, particularly in the relatively large quantities that are often required for vaccination.

The Wrapp lab uses structure-based design to stabilize these tricky viral proteins into conformations that are optimal for antigen presentation. These efforts are facilitated by experimental techniques such as cryoEM and X-ray crystallography, as well as more recent advances in machine learning and artificial intelligence. Stabilizing modifications generally have dramatic beneficial impacts on the yield of recombinantly expressed proteins, allowing for material to be produced in quantities that permits thorough downstream biophysical and immunological characterization. Not only does this stabilization allow for easier in vitro expression, but because many of these proteins represent potential vaccine immunogens, this work also has direct translational implications for human health.