Proteins carry out many fundamental life processes, and the ways they work are very similar to the machines we see around us. High-resolution details of these tiny protein machines are essential for understanding their mechanisms and for developing drugs to interfere with their functions. 

The Liao lab focuses on understanding the structure and function of protein-DNA/RNA complexes and membrane proteins, for example, RAG12 complex, CRISPR, ERAD protein channel and ABC transporters. One particular interest is to reveal the mechanisms of how proteins sense, move and convert specific lipid molecules. This can be achieved by obtaining high-resolution structures of lipid-interacting proteins, and by studying the dynamic protein conformations in native membrane environment.

Cryo-EM is a rapidly advancing research area, powered by the knowledge of biology, physics, material science and computation. Single particle cryo-EM is a ‘rising star’ in structural biology, providing remarkably versatile and powerful tools to study the structure and function of biological macromolecules. Compared to more traditional methods such as X-ray crystallography and NMR spectroscopy, cryo-EM demonstrates a number of important advantages, including small amount of sample required for EM analysis, flexibility in studying different functional states, and computational sorting of mixed conformations. Exploiting recent advances of cryo-EM, we aim to obtain the complete “molecular movie” for protein machines in action.