Research

Cells are surrounded by membranes. A variety of cellular processes, such as substance transport and cell signaling, are carried out by proteins embedded in the membrane. Membrane proteins are targets of more than half of all modern pharmaceutical drugs, and they are notorious for structural determination. Recent breakthroughs in cryo-electron microscopy (cryo-EM) provide unprecedented tools to study structures of membrane proteins in their native environment and hence greatly improve our mechanistic views. The Mi laboratory exploits structural, biochemical, and genetic approaches to understand the structures and functions of membrane proteins and identify potential drug targets.

Gram-negative bacteria are characterized by two membranes: an outer membrane (OM) and an inner membrane (IM). The OM forms the outermost permeability barrier to protect the cell against both large polar molecules and hydrophobic agents. Compared with their Gram-positive cousins that only have a plasma membrane, Gram-negative bacteria are intrinsically more resistant to antibiotics because of their unique asymmetric OM, with lipopolysaccharides (LPS) in the outer leaflet and phospholipids in the inner leaflet. We are interested in how LPS and phospholipids are balanced to maintain the asymmetry and integrity of the OM at the molecular level. Our recently published YejM/LapB complex structure provides the first hint on how LPS and phospholipids syntheses are coupled and leads to new targets for developing the next generation of antibiotics.

We have collaboration projects with several labs to determine structures of membrane proteins, which assist structure-based drug development. Collaboration projects include receptor tyrosine kinases, and membrane proteins involved in epileptic and infectious diseases.