A cartoon of protein folding during translation at the ribosome.

David Balchin : Protein Biogenesis Laboratory

We study how cells make proteins and fold them into functional molecular machines.

Almost every biochemical reaction in our cells is carried out by proteins. These tiny molecular machines are made as straight chains, but to work properly they must fold up into intricate 3D shapes. Many different shapes are possible, and each protein must go through precisely the correct sequence of folding events to end up as a working machine. 

Our cells perform this impressive feat of molecular origami millions of times every hour for more than 20,000 different proteins. But the folding process is not always perfect, and small errors can have severe consequences. Incorrectly folded proteins are a hallmark of aging, and a cause of neurodegeneration and type II diabetes. 

The synthesis and folding of new proteins are carefully coordinated and closely supervised to avoid toxic mis-folding, but we are only beginning to understand how this works. To unravel the details, my lab makes and folds proteins under controlled conditions in a test tube. By building the machinery of protein folding ourselves, we want to learn exactly how this remarkable process occurs in cells and what causes it to go awry in disease.