Molecular chaperones assist the folding of virtually all cellular proteins. Despite years of intensive study, the fundamental question of how chaperones facilitate protein folding remains unclear. Whilst molecular chaperones in the cytosol use the energy of ATP hydrolysis to control substrate binding, folding and release, how chaperones in the bacterial periplasm assist folding in the absence of ATP is unknown. Recent experiments have identified the substrates of the periplasmic chaperones Spy, Skp and SurA. Some of these chaperones assist folding of both water-soluble and membrane proteins, raising fascinating questions about how a chaperone is able to recognize its substrates, to release them in a controlled fashion and to assist folding. In this project the student will use biochemical and biophysical methods to determine how periplasmic molecular chaperones recognize their substrates, assist folding and, in tandem with each other and the Bam complex, create the folding pipeline required for bacterial growth and survival.