research

Computational imaging and discovery, from molecules to cells.

From noisy images to molecular discovery

We combine physics-based modeling and AI to detect molecules and characterize their structural states directly from cellular cryo-EM/ET data. Our ultimate goal is to understand how the structures of molecular machines relate to their functions in cells, and to use these insights to guide the design of more effective therapeutics.

01 DiffPose

Faster in situ template searches

We speed up projection matching so cellular cryo-EM images can be searched against many molecular templates. Our goal is to make large-scale in situ searches practical for identifying molecules directly inside cells.

Watch DiffPose refine a molecule's orientation, step by step.

02 GisAPR

Refining atomic models directly from images

We adjust the atomic model to match observed 2D cryo-EM images directly. This lets us refine molecular structures without first reconstructing a 3D map.

A molecular ribbon model with a highlighted region and two structural conformations shown in purple and cream.
Molecular models connect the positions of atoms to what we see in an image.

03 Sub-50 kDa

Resolving structures below 50 kDa

We use known structures as templates to select and align images of proteins smaller than 50 kDa. This improves single-particle cryo-EM reconstructions, revealing clearer details of ligands and their binding pockets.

Side-by-side density for residues 222-227 and ATP in protein kinase A from a conventional single-particle map, the 2DTM template, and the 2DTM reconstruction.
A clearer view of protein side chains and ATP in a ~41 kDa protein kinase A complex, comparing the conventional single-particle map, the 2DTM template, and the 2DTM reconstruction.

04 2DTM p-value

Detecting small and rare molecular targets

We developed the 2DTM p-value, a statistical score that helps distinguish molecular signals from noise in cryo-EM images. It improves detection of small and rare targets while controlling false positives.

Scatter plots compare conventional 2DTM detection thresholds with the p-value approach, highlighting true positives.
A new detection score helps separate molecular signals from noise.

05 In situ classification

Distinguishing molecular states inside cells

We distinguish different stages of ribosome assembly directly in cellular cryo-EM images, without reconstructing a 3D map. Using multiple templates and a statistical model, we classify individual ribosomes and map where these distinct states occur inside cells.

Cryo-EM images and analysis show different 60S ribosome maturation states in the nucleus and cytoplasm of yeast cells.
Distinct 60S ribosome maturation states classified and mapped inside yeast cells.

These projects include current work and earlier research by Kexin Zhang with collaborators. Explore each project for more figures, animations, and publications.