"Although I could go on to Kyoto University right after high school, I felt a slight regret that I compromised without fulfilling my first ambition. As such, after enrolling at the university I could not concentrate on my studies, and I did kendo all the time."
However, a turning point came to him as a freshman of Kyoto University in 1977 when he read newspaper articles regarding molecular biology―an academic discipline unknown to him at that time―pursued by Dr. Susumu Tonegawa and other scientists.
"This was my first happy meeting." said Professor Mori.
Molecular biology, which seeks to clarify life phenomena at a molecular level, i.e., at a sub-cell level, has proved the genetic code is conserved from Escherichia coli to humans. The emergence of molecular biology significantly impacted him, who had disliked biology until then because he thought the subject required him to learn everything by heart. Suddenly he developed a great interest in biology, and transferred to the Faculty of Pharmaceutical Sciences in his second year at the university, with the objective of pursing studies in the field of biology.
He then joined the laboratory of Professor Ikuo Yamashina, and started to study biochemistry under the guidance of Dr. Toshisuke Kawasaki. This was because there were no faculty members specializing in molecular biology in the Faculty of Pharmaceutical Sciences. Looking back on those days, Professor Mori said, "The experience I gained working on biochemistry served as preparation for conducting my current research. In addition, I truly enjoyed biochemical research."
Fascinated by the profession of researchers who put their utmost into resolving a question without an answer, he was determined to pursue his career as a professional researcher. At that time, however, it was difficult to remain at the university in Japan; as there were many PhD holders/candidates who had completed their doctoral courses but could not find employment. When he was worried about the situation, Dr. Kyozo Hayashi, who had been an associate professor under Professor Yamashina, invited Mori to accompany him to Gifu Pharmaceutical University, on the occasion of his appointment as Professor there. Then Mori left Kyoto University in the second year of the doctoral course to become an assistant professor at Gifu Pharmaceutical University in 1985.
At Gifu Pharmaceutical University, he continued to conduct research in the field of biochemistry. As a university faculty member, a positon that he had coveted, he worked hard and published as many as eight papers in the four years, following the policy of Professor Hayashi who encouraged him to author many papers. However, Professor Mori gradually began to feel that the research project he was then engaged in was not promising for his future. He suggested other research projects, which were not accepted.
At this point, he was determined to take on a major challenge. He decided to resign his position as a faculty member. Recalling this decision, Professor Mori stated that "Every research involves difficulties. If I have to undergo certain difficulties at any rate, I would rather do something more interesting and important and something with great potential for development."

"I wanted to figure out why my research was unsuccessful, and whether it was because of the environment or because of the limitation to my ability." With this idea in mind, he went to the United States, a mecca of molecular biology, but it was hard to find a laboratory that would accept him. Finally he became a postdoctoral fellow at the laboratory led by Professor Joe Sambrook and Professor Mary-Jane Gething, at the University of Texas.
In actuality, he had planned to move to the East Coast or the West Coast after learning English and molecular biology for two years or so in the laboratory. Unexpectedly, however, it was there that he had his second happy meeting―he encountered unfolded protein response (UPR), which became his current research theme.
He went to the United States in 1989. Just the previous year, Professors Sambrook and Gething had announced their report on the presence of UPR. Professor Mori said "I was happy to be able to engage in UPR research from its beginning. I had this good fortune because I dared to come to the United States."
Professor Mori said with a laugh that he realized that he had a strong ability to accomplish research. He added, "I was right not to give up. Good can come out of misfortune. Everyone can find his/her place anywhere. You don't have to be pessimistic."

Unfolded protein response (UPS) is, so to speak, cellular response to control the quality of proteins." In cells comprising an organism, many subcellular organelles are concentrated and fulfill their individual functions. One of these subcellular organelles is the endoplasmic reticulum (ER), which has a net-like membranous structure. With a protein synthesis function, the ER can be called a "factory."
Within the ER, proteins are synthesized as chains of amino acids linked together like beads on a string, forming a three-dimensional structure that is suitable for playing their respective roles as assigned by the genetic code. Originally, proteins have the ability to naturally form a three-dimensional structure. This formation process is assisted by proteins called "chaperones" that are present within the ER. By the way, "chaperone" in French means a female assistant.
Even with the assistance of chaperones, occasionally a protein folding defect may occur, resulting in unfolded or misfolded proteins. An ordinary factory not only produces products but also manages their quality. The same also holds true with the ER. Professor Mori explains: "The endoplasmic reticulum detects defective proteins, and tries to correct them."
Various environmental changes may cause abnormalities in the ER. Sometimes the number of defective proteins may increase too much, and good proteins may change into bad ones at other times. Even under ER stress conditions, cells have a mechanism to maintain the ER homeostasis by overcoming the stress. This is called "unfolded protein response (UPR)."
Specifically, if defective proteins have accumulated in the ER, the ER stress signal is transmitted to the nucleus, so as to increase the number of chaperones to enhance the capacity of protein production. At the same time, the UPR also increases the number of the "removal devices" to decompose and remove defective proteins, thereby enhancing the capacity of degradation of unfolded/misfolded proteins.

How about the mechanisms of unfolded protein response? In attempt to clarify these mechanisms, Professor Mori formulated three hypotheses.
First, he hypothesized that there should be something like an "eye" to monitor the state of the ER. Following the advice of the professors at the University of Texas, he use yeast ER to check whether the "eye" functioned or not. The number of yeast cells he had checked amounted to 100,000. Finally, he discovered IRE1, a sensor molecule that detects the accumulation of defective proteins. "I made this discovery in 1993, which was my first feat which earned me distinction as a researcher."
Regarding IRE1, Professor Peter Walter of the University of California, San Francisco, published a paper, ahead of Professor Mori. However, as the IRE1 paper authored by Professor Mori had more detailed content, it was presented by the same scientific journal two months later.