Professor Bukau is concerned with the mechanism and regulation of protein folding in cells via chaperones in a normal state and under stress conditions such as heat shock, which can lead to misfolding, and with the balance of protein formation and degradation (via proteases) and the associated quality control in the cell. Among other things, he developed a model of the DnaK/DnaJ/GrpE system of chaperones. He also investigated the spread of protein misfolding to neighboring proteins that occur in neurodegenerative diseases.
In 1999 he received the Gottfried Wilhelm Leibniz Prize, in 2008 a Heidelberg Molecular Life Sciences Award and in 2005 the Leopoldina Research Award. In 2005 he became a member of the Leopoldina and in 2013 of the Heidelberg Academy of Sciences and Humanities. In 2001 he became an EMBO member. In 2017, he received an ERC Advanced Grant and the Research Award of Heidelberg University.