The success of key nuclear processes like transcription and chromosome segregation depend on the correct 3-D organization of macromolecular complexes inside the cell. Failure to regulate the spatial distribution of these complexes can contribute to cancer and birth defects.

Schematic of nucleosome (blue) packing with "megacomplexes" in fission yeast. From Cai, 2018.

We are also investigating how cells coordinate large protein-based machines to segregate chromosomes.

Schematic of Dam1C/DASH (green) being driven toward the minus end (left) by the shrinking kinetochore microtubule (magenta). From Ng, 2019.

We use yeasts as model systems. The degrees to which they can be controlled allow us to ask extremely precise questions. Their superb synchronization properties allow us to "phase" the cells in meaningful biological states. 

Movie of chromosome (cyan) in interphase and mitotic fission yeast courtesy Dr. Shujun Cai.

We use electron cryotomography (cryo-ET) to see the nanoscale details of large macromolecular assemblies within organelles and cells.

Left: tilt series. Right: tomogram.

To make sense of our cryo-ET data, we use advanced image-processing workflows. These tools are as important to us as our pipettes!

Left: tomogram. Middle: moar cores. Right: template match results.