![リガクル[RIGAKU-RU] Exploring Science](/ja/rigakuru/images/top/title_RIGAKURU.png)
Dr. Ai Niitsu is the PI (principal investigator) of the Biomolecular Dynamics Research Team at a laboratory established in January 2024 on RIKEN’s Yokohama campus. Her research focuses on membrane proteins and peptide design in synthetic biology, a field that aims to understand how proteins work by creating them.
Perhaps she never stops smiling when talking about the difficulties of her work precisely because of the non-stop challenges that membrane proteins pose. Why does this research topic take longer than usual time to yield results?
Scientists have to be “stupid”
"When I face something that seems to be going wrong in a project, I tend to doubt that the problem is impossible to solve. I often think that there might be a way to solve the issue," says Niitsu, adding that she is a person who wants to take on a challenge the riskier it is. She credits her daringness to the encouraging words of “Scientists and smarts,” a book written by Torahiko Terada.
“To be a scientist, you have to be smart…but you also have to be stupid.”
Of course, having a challenging research topic is not everything. Niitsu was interested in understanding living organisms and was charmed by the fun of design in chemistry. So, she began researching membrane proteins, important chemicals found in the cell membranes of living organisms, and membrane peptides, even shorter versions of these proteins. Her professor warned her that membrane proteins took much longer to study than water-soluble proteins, making them difficult research subjects.
"People around me were choosing research topics along the lab's main theme. However, being told it would be difficult only lit my fire as a researcher. To be honest, as a fourth-year undergraduate student, I had no idea how difficult it would be. Making full use of my “stupidity” I declared “If it is that difficult, I want to do it even more!” and decided to go down that path. Once I had first-hand experience, I found that it took more than twice the time it would normally take to conduct experiments and analyze data. It was hard work, but I could not back out anymore," she recalls.
Even after that, she continued to tackle time-consuming topics. Her postdoctoral research topic was such a long shot that it prompted questions like “Your initial contract period may not be long enough to publish a paper. Are you ready for the challenge?” She started the project from scratch in the laboratory, designing peptides that self-associate in membranes to form uncollapsible pores. The resulting papers were published five and nine years later, both in Nature Chemistry. The project had a great impact because it was a topic that smart people avoided.
Design x Simulation x Measurement
From January 2024, the Biomolecular Dynamics Research Team led by Niitsu has been conducting research by skillfully combining three methods: designing membrane proteins, making predictions with molecular simulations, and making measurements in the laboratory.
Going back and forth between design, simulation, and measurement is an intricate process. However, Niitsu did not learn each skill with the aim of combining them later. Rather, it was the result of her drive to understand membrane proteins better. She asked for help and instructions even from professors she had never talked to before, and the skills she had acquired along the way came together by chance.
“I am grateful for the labs and the professors who have taken me under their wings. As a PI, I want to make sure to respect and be open to the ideas of the people I will be working with,” Niitsu says.
What I cannot create, I do not understand
Physicist Richard Feynman once said, “What I cannot create, I do not understand.” This is precisely how synthetic biologists including Niitsu think about understanding the rules of folding amino acid sequences (sequence-structure relationships).
It might seem that these rules have already been discovered by AplhaFold2, an AI software developed by DeepMind. However, the software's accuracy is reduced for membrane proteins and artificial protein sequences. Moreover, the information obtained about dynamically folding proteins is limited. In other words, there are folding rules waiting to be discovered. Niitsu says, "My scientific interest lies in clarifying this part of the puzzle.” Creating membrane proteins that function as intended deepens our understanding of living organisms.
Cherishing the thrill of understanding
Conducting research that breaks new ground in a field is extremely challenging. While there is a potential for great impact, there may be a long waiting period before results can be published in a scientific journal.
“I am usually just grinding when doing research, but every once in a while, I have a really good day,” Niitsu says. “It is not always a great discovery, but there are moments when a path opens up. When I finally experience the thrill of understanding, I cannot resist it. 99% of the time I am grinding through obstacles to experience such moments 1% of the time (laughs),” she explains her motivation to continue taking on research topics that have a high risk of failure in addition to the struggle. She continues.
“I believe that the students who enter the Faculty of Science are those who have felt the thrill of understanding. I encourage these students to make their choices based on what allows them to experience such thrill. If they do so, they will be able to persevere no matter what happens later.”
Laboratory website: https://www.bdr.riken.jp/ja/research/labs/niitsu-a/index.html
Year of the interview: 2024
Interview and text: Naoto Horibe
Photography: Yuki Ide
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