Ben Engel

Cells accomplish the biochemical reactions of life by concentrating their proteins into a variety of subcellular compartments called organelles.  Our group explores the relationship between the form of the organelle and the function of its resident macromolecules.  How does organelle architecture direct molecular function, and reciprocally, how do macromolecules sculpt and shape organelles?

To investigate these questions, our group uses cryo-electron tomography (cryo-ET) to directly visualize macromolecules “in situ”, within the native cellular environment.  First, we rapidly freeze the cells in non-crystalline vitreous ice, preserving them in a state of suspended animation.  Next, we use a focused ion beam to thin the cells, followed by cryo-ET to acquire 3D images (called tomograms) of the native cellular interior with molecular resolution.  These tomograms enable us to solve molecular structures directly within the cell, at sufficient resolution to distinguish different conformational states and interaction partners.  We then map these structures back into the cellular volume with nanometer precision, allowing us to analyze molecular organization within the cell at the scale of single molecules.