Kazutoshi Mori (Kurashiki, Japan, 1958) graduated from the Faculty of Pharmaceutical Sciences at Kyoto University in 1981. After obtaining his PhD there, in 1985 he was appointed Assistant Professor at Gifu Pharmaceutical University. He spent the years 1989 to 1993 in the United States, working as a postdoctoral fellow at the University of Texas Southwestern Medical Center. It was there that he began his studies of the unfolded protein response, setting the course for his subsequent research endeavors. In 1993 he returned to Japan, initially to the HSP (Heat Shock Protein) Research Institute in Kyoto where he remained until 1999. That same year he was appointed Associate Professor at the newly founded Graduate School of Biostudies at Kyoto University, and four years later took up his current position as Professor of Biophysics in the university’s Graduate Science School.
When the cell’s capacity to fold proteins is exceeded by the quantity of proteins in the pool or when folding conditions are subject to stress (due, for example, to lack of oxygen or nutrients), proteins cannot fold themselves correctly and acquire toxicity through aggregation. The next step is to either repair or remove them, very much as you would deal with a rubbish bin that needs emptying. This mechanism which does so is known as the unfolded protein response (UPR). While this machinery is in motion, the cell puts its protein production processes on hold until such time as it can reboot and resume normal function. Kazutoshi Mori and Peter Walter discovered this process simultaneously but independently (they have never signed a joint paper), and published their findings in Cell in the same year, 1993. They identified an enzyme, IRE1, that acts as a sensor of unfolded proteins and sends alarm signals to the cell nucleus to correct the misfolding and eliminate misfolded proteins. Both used yeast cells to start their research, since they operate like test tubes in a living system. And the final proof came when they were able to show that the salient features they had discovered in yeast also held true in human cells.