Mechanics and Variation in Host-Pathogen Engagement

 

Virus Structure and Dynamics

FusionProteins_Gallery_small_edited.png

Our lab at the University of Washington studies enveloped virus entry and the dynamic conformational changes carried out by viral fusion protein machines that drive fusion of membranes and genome delivery. 

To understand how a dynamic process like membrane fusion and cell entry are carried out, we focus on imaging the entire virus instead of just isolated components as has often been done in the past. This enables us to visualize and monitor the fusion proteins in their biological contexts on virus particles where membranes and matrix proteins that modulate the fusion protein function are still present and where the proteins can interact with host receptors and target membranes.

In addition, to go beyond structure and start understanding function, we also need to add the dimension of time by examining  protein and membrane dynamics. Structure may tell us about the anatomy of a protein or a virus, but dynamic transitions and conformational change tell us about its physiology, how it moves and works as a machine.

Fusion_Pathway_Fig_small3.png

HOW WE INVESTIGATE DYNAMIC PROCESSES

Tracking, capturing, and imaging dynamic processes require techniques that can probe conformational fluctuations and structure under native conditions. We use cryo-EM, cryo-electron tomography, structural mass spectrometry, fluorescence microscopy, and fluorescence spectroscopy to probe and dissect the changes viruses and pathogens undergo during invasion of cells.

HDXMS_HA_Fig.png
 

© Lee Lab UW 2021