Working in a stimulating, constantly changing environment is essential for scientific research. This can only be achieved by challenging yourself to leave your comfort zone and gain international experience. Dr. Arnout Voet travelled from KU Leuven to RIKEN, a world class research institute, in Tokyo, Japan. He also made the move from computational drug design to designing novel proteins with putative usage in bionanotechnology and drug delivery. We spoke with him about his life in Japan, traveling, “Pizza” proteins and the importance of changing research environments.
Why did you change fields?
Arnout Voet: “I decided to switch to another field because I was already experienced in designing small molecule drugs and I needed a new challenge in a novel and unexplored field. Something where I thought I could make a major contribution”
How is protein design different from drug design?
“Contrary to drug design, where we try to design a key that fits in a lock, in protein design we are trying to design the lock (eg. a flexible protein, with flexible backbone and yet unknown amino acid sequence) to fit around the key, while making sure the lock is not only a good match in shape but also actually still able to open and close correctly (eg. a fully functional active enzymatic site). Such novel, designed proteins could be used in the biopharmaceutical and bionanoelectronic field. For example, as a delivery system that can be triggered to specifically release highly toxic drugs exclusively at the cancer sites within the patient. Also, we managed to grow the smallest nanocrystals ever inside a designed protein network. This method could be applied to produce quantum dots (nanocrystals made of semiconductor materials) for optical, electronic, and cellular imaging applications. They are currently being produced using inorganic chemical synthesis, but we could synthesize them in an eco-friendly aqueous environment using a designed protein network. We are contributing to an ongoing research to make new enzymes to catalyze specific reactions for eco-friendly biofuel production.”
You designed a “Pizza” protein. What does it do and what does it have in common with Italian fast food?
“One of my friends, now a collaborator, was trying to modify a natural ring-shaped protein for bionanotechnology applications. The protein had a modular structure and consisted of several repeats of the same motif that self-assembled in a 11-fold symmetric ring motif. They were interested in a variety of applications which were out of reach because of the inability to create asymmetric modifications and modulate the self-assembly. Therefore, I decided to computationally design them using a monomeric symmetric protein that could be sliced according to their preference. A small number of non-symmetric ring shaped repeat containing proteins exist in nature. These are believed to originate from genetic duplication and fusion events during evolution. After the fusion event, the ancestral protein would most likely be a perfect symmetric monomeric protein, whereas before fusion it would have been a multimeric (sliced) protein. Therefore we decided to reverse-engineer this evolutionary process and designed a protein which had 6 identical repeats, was circular in shape and could be sliced into smaller pieces and assembled back into its original shape.
One Friday evening in the Riken Wakoshi cafeteria, we were having drinks and food with some fellow researchers. We ordered a pizza, which was delivered cut into 6 slices, and because of the similarity in shape and the tolerance towards slicing I decided to call my protein “Pizza” at that exact moment.”
How did you end up in Japan?
“I once gave a talk in Philadelphia (PA) and I was offered a position in Nashville by a professor in the audience. I went to visit that lab in 2011, but I could not imagine myself living in Nashville. At that time the earthquake, and resulting tsunami, had recently occurred in Japan. Because of all the attention that Japan was getting in the media I started to think more about this place as a potential country to relocate to. Shortly before I moved, a Japanese scientist from RIKEN was appointed as a professor at our department at the KU Leuven. Back then, The RIKEN institute was building the world’s most powerful supercomputer (kei computer) and also has the world most intense synchrotron radiation facility. The institute is also world famous for computational and structural biology. Moreover, the laboratory that I wanted to join had been doing drug design in both the academic and industrial settings with world acclaimed results, which was one of my areas of expertise, but also was interested in protein design, which was exactly what I wanted to learn. I have always been passionate about the Asian culture and it inspired me to look for a post-doc position at this laboratory in the RIKEN institute to expand my international network.
Originally I only planned to join the laboratory for one year, but I quickly realized that one year was not enough time to learn all of the things I was interested in, or make significant progress.
In my opinion, it takes a few years to really benefit from changing ones research environment. And as such, 4 years later I am still in Japan. I started in a pure computational environment but am now also working in a protein crystallography laboratory as well.”
You used to be a travel guide for many years; did you visit Japan before you moved there for work?
“No, although my previous travels had been concentrated in Asia. I came to Japan with the intention to explore more of Asia, while doing research. However, after one year I realized that I had hardly left Tokyo. I had been busy with research during the day and in the evenings I took classes in the modern Japanese martial art, Iai-do. During the weekends I explored the different neighborhoods of Tokyo, took pictures and embarked on a quest to find the best place to eat Japanese noodles, ramen.”
What are the differences between living and working in Japan and in Belgium?
“At work, the main difference is that the Japanese work very hard and longer hours. This does not mean they get more done, but they take pride in being careful and precise. They do not think about planning/multi-tasking their work so that it fits into a 9-to-5 schedule, as many European employees may do. Also, living in Japan is actually more convenient than living in Belgium. Many shops are open 24/7, or at least till 22h30, so you don’t need to worry about grocery stores closing before you are home from work. You can even buy a new pair of jeans at 3AM if you wish.”
Tokyo is one of the biggest cities in the world, however it still is very organized and clean. It is very busy during rush hour, but outside of the rush hours the city actually has a relaxing, enjoyable atmosphere.
Do you have plans to move to another city in the future?
"I had some doubts when getting on the plane to Japan, leaving my happy comfortable scientific life in Belgium behind, but it was the right thing to do. It has been an essential experience to further develop myself as a scientist. I have learned new techniques, explored different fields, and created an interdisciplinary international network of scientist-friends. Also, on a personal level it has been an amazing experience. I don’t want to leave Japan, however after 4 years it is time to move on. I feel I need another scientific challenge in another place where I can do something new. However, before I leave Japan, I still have a lot of experiments to finish, a few prefectures to visit and mount Fuji to climb.
As a scientist you should prove yourself among several groups, explore new areas and acquire new insights.
Although I initially had some difficulties adapting, what I like most about Japan is the kindness and helpfulness of the people, the amazing food and drinks, the Japanese way of life, and of course my friends. I am not sure what my future will bring, but when I will leave Japan, I will probably miss it more than I missed Belgium during my time here. However, I have loads of nice memories and experiences to take with me as I continue my scientific journey. Actually, one of my favorite memories from Japan will be a personalized manga-comic about my research. It was drawn to explain the Pizza protein design to the broad audience of one of Japan’s major newspapers in the science section. I will make sure it is framed and put in a nice spot in my next office.”
Voet, Arnout RD, et al. "Computational design of a self-assembling symmetrical β-propeller protein." Proceedings of the National Academy of Sciences 111.42 (2014): 15102-15107.
Voet, Arnout RD, et al. "Biomineralization of a Cadmium Chloride Nanocrystal by a Designed Symmetrical Protein." Angewandte Chemie International Edition 54.34 (2015): 9857-9860.