As a new graduate student at the University of Wisconsin–Madison, James Bardwell demonstrated an ability to set conventional scientific wisdom on its head. Studying a heat shock protein later shown to be essential in protein folding, he demonstrated that heat shock proteins are conserved from bacteria to humans.
Bardwell continues to study protein-folding catalysts and chaperones—the molecular machinery that helps proteins reach their proper shape—and to generate surprising insights by using Escherichia coli as a model system. The research may generate a better understanding of disorders such as cystic fibrosis and Alzheimer's disease, which are thought to be caused by proteins failing to fold into their proper three-dimensional shape.
Bardwell focuses on disulfide bonds, which act like bolts or stiffening struts to keep proteins in their right shape. He and his colleagues discovered a protein called DsbA and showed that it donates disulfides to secreted proteins and, in doing so, catalyzes their folding. Using E. coli as a model organism, his group described the biochemical pathway cells use to generate disulfide bonds.
Bardwell and colleagues recently found that a mutated E. coli strain, lacking the disulfide bond pathway, developed an alternative way to make disulfide bonds, recruiting a protein called thioredoxin to build an iron-sulfur cluster that could form disulfides.
Bardwell plans to continue to force bacteria to acquire new means of performing fundamental biochemical reactions. He will engineer bacteria to evolve other ways to make disulfide bonds and will track the coevolution of proteins and their protein-folding catalysts. He also will use disulfide bond formation as a tool to investigate protein folding as it occurs in the cell. Bardwell's lab will also explore the three-dimensional structure and function of newly identified heat shock proteins.