Zhen Chen

How do cells build themselves?

During development, stem cells transform into highly specialized cells such as sperm, neurons, and muscle cells. This process requires cells to dramatically reorganize their internal architecture, assembling precise molecular machines and organelles that enable specific functions—movement, signaling, and force generation.

For example:

• How is a sperm tail assembled to generate rhythmic beating motions?
• How is a synapse built to enable rapid and precise signal transmission?

At the most basic level, cells must produce the right proteins at the right time, move them to the correct locations within the cell, and assemble them into functional complexes that hold the cell together, drive chemical reactions, or generate dynamic force. All instructions governing these processes are encoded in specific molecular interactions and disruptions can lead to defects in complex cellular systems and diseases.

Beyond conventional approaches to studying cell differentiation—including cell biology, single-cell methods, biochemistry, and computational modeling—we develop in situ cryo-electron tomography to visualize macromolecular machines in their native cellular environment at near-atomic resolution. This high-resolution approach enables the discovery of previously unknown molecular assemblies and links their structural organization to cellular function and developmental state.