As the second seminar speaker Dr. Malaiyalam Mariappan, PhD invited Dr. Kazutoshi Mori to talk about “Dynamics of Function and Regulation of the Endoplasmic Reticulum” on February 9th 2021
With his first international online talk premiered during the CB seminar series, Prof. Dr. Kazutoshi Mori presented his recent work on UPR. Even though the time zone difference makes it more difficult, ‘since [he] went to bed at 3 am that day’, Dr. Mori honored us with an interesting and inspiring talk.
An unclear path towards a clear goal – to be a scientist!
Prof. Dr. Mori’s interest has always been in science and technology from an early age on. ‘I loved to read comics {Japanese manga} in my childhood. Some of them became American movies, such as Astro Boy and Speed Racer’.
[Author notes: ‘Astro Boy’ is a science fiction manga (Japanese comic) in a futuristic world where robots (androids) live among humans, while ‘Speed Racer’ focuses on automobile racing. Both manga are among the most successful franchises of all time.]
Analytical thinking showed his talent for Mathematics and Arithmetic, Curiosity got him to read about science in the newspaper. Inspired by the first Japanese Nobel prize winner in Physics Dr. Hideki Yukawa in 1949, he first wanted to study Physics [2]. However, his enthusiasm about molecular biology grew, being amazed by the research of Dr. Susumu Tonegawa, who was awarded the prize in Physiology or Medicine 1987 [2]. Dr. Mori got more and more curious and passionate about molecular biology, unfortunately ‘not many labs took interest in it in Japan in the 1980’s’. And he desired to be a scientist. He made the decision to quit his secure and permanent position at the university in Japan and go ‘to the USA to learn Molecular Biology at the age of 30’.
‘Fortunately, Joe Sambrook (one of the three authors of “Molecular Cloning” which was called Bible in Molecular Biology) and Mary-Jane Gething at the University of Texas Southwestern Medical Center at Dallas, Texas accepted me in 1989.’ One year prior to that, ‘they found that mammalian cells are equipped with the UPR, but no mechanism or molecules were known at that time’. Clues were found earlier in 1984, when the increase of glucose regulated proteins (GRP) was observed after cell starvation (Lee et al., 1984 [4]). Also the idea of protein folding by helper proteins, chaperones, was postulated but not involving GPR proteins. In fact, the connection between GRP and chaperones was only hypothesized upon observing that ER resident GRP78 was similar to HSP70, a cytosolic chaperone (Munro and Pelham, 1986 [5]).[3]
A response to open questions
With Joe Sambrook and Mary-Jane Gething’s finding that the protein GRP78 can bind misfolded protein in a chaperone like manner, the door was opened for Dr. Mori to provide the response:
In a mutant screen using yeast, Dr. Mori found the protein IRE1 independently in parallel with Peter Walter [6], [7], which ultimately founded the discovery of the ER based UPR. [3] In his ‘10 years as a Postdoc, of which 4.5 years were spent in the US and 5.5 years in Japan’, he explored the mechanism of the newly found UPR. At the age of 40 Dr. Mori finally became an Associate Professor and 5 years later he holds the position as Professor of Biophysics. ‘Hard work with proper strategy to survive was very important for my career.’ A view that was awarded, often jointly with Peter Walter, with important international prizes: Wiley, 2005; Gairdner, 2009; Lasker and Shaw, 2014; and Breakthrough, 2018; along with several national awards and merits. For Dr. Mori ‘(and to [his] family) the own unique style of each ceremony is unforgettable.’
The way of the sword
Besides science Dr. Mori is also passionate about Kendo [jap. ‘way of the sword’]. A traditional Japanese martial arts form which he actively practices for many years already. ‘the foot movement in Kendo is very different from those in Western sports.’, which encouraged him to try this sport as a junior high school student. He describes himself as ‘unathletic’, but ‘[his] choice [in Kendo] turned out to be very good’. ‘In Kendo we use bamboo sticks, that’s why technique is more important than power’ [8] The sport accompanied him through his time in High School, Kyoto University ('practicing up to 6 times a week') and even after graduation ('practicing 2 times a week even at Dallas'), Kendo literally chaperoned him. ‘I obtained 5-dan (fifth ranking, an instructor level) at the age of 40.’ A huge achievement among the successful science. Even as an Associate professor, when he ‘could not find time to play Kendo for [himself]’, he is still actively involved in the sport. ‘Instead, I am instructing elementary school students and junior high school students once or twice a week to show “a sound mind in a sound body”.'
We can go forward – believe in yourself! [Breakthrough Laureate interview 2018]
The nature of the sport, where physical benefits in young age does not matter much, makes it possible to be ‘active players throughout our lives’ and ‘can go forward’, as Dr. Mori stated in a Laureate interview for the Breakthrough prize in 2018 [8].
Going forward together is what is highlighted when looking at the website of the Mori Lab as well. A blog with up-to-date science and stories. A gallery with lots of photos from events and team building sessions outside of the lab bench. All of this accounts for a good work atmosphere which includes a ‘lab meeting on the first day of every week [to] discuss’, making it possible to manage all the projects and experiments from his currently 24 Bachelors, Graduate students, Technicians, and Post-Docs.
10 years from now
‘Universities in Japan have automatic retirement system for faculty members’, which is different from the system in the US or Europe, where the retirement can be supposed but does not have to be enforced. ‘I will retire from Kyoto University 3 years later. If I could continue my research, I will spend more time on applicational aspects of the UPR.’ With the time restriction in sight, and fully focused, the Mori lab is working on 'three papers currently:
1) Effect of persistent ER stress on embryonic development in Medaka fish
2) Mechanism of neurodegeneration
3) Role of the UPR in tumor growth in nude mice
covering a broad area on the ER.’
Hard work with proper strategy to survive was very important for my career.
Dr. Kazutoshi Mori
Let’s watch out for the great upcoming science!
(The interview was performed via eMail with questions developed by Mai Ly Tran. The article was compiled from answers from the interview questions and sources stated below.)
References:
- http://www.upr.biophys.kyoto-u.ac.jp/en/
- https://www.sankei.com/west/news/141014/wst1410140009-n1.html (jap)
- https://www.pnas.org/content/111/50/17696
- Lee AS, Bell J, Ting J (1984) Biochemical characterization of the 94- and 78-kilodalton glucose-regulated proteins in hamster fibroblasts. J Biol Chem 259(7):4616–4621
- Munro S, Pelham HR (1986) An Hsp70-like protein in the ER: Identity with the 78 kd glucose-regulated protein and immunoglobulin heavy chain binding protein. Cell 46(2):291–300.
- Cox JS, Shamu CE, Walter P (1993) Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase. Cell 73(6):1197–1206
- Mori K, Ma W, Gething MJ, Sambrook J (1993) A transmembrane protein with a cdc2+/CDC28-related kinase activity is required for signaling from the ER to the nucleus. Cell 74(4):743–756.
- Laureate interview breakthrough prize 2018 https://breakthroughprize.org/Laureates/2/L3825