Ms. Satoko Kinoshita, who supports researchers with her outstanding communication skills, introduced me to the next interviewee, Dr. Tomoki Ishibashi, saying, “He is doing some seriously fascinating research!” She gave him her full endorsement, explaining that he was working on uncovering mysteries of biology in a physics laboratory and could talk about complex topics in an engaging manner. So, I sat down with him to find out exactly what he was working on.

IK refers to interviewer Izumi Kanchiku and TI refers to Dr. Tomoki Ishibashi.

The appeal of continuous biological hierarchy

IK: Please tell me about the topic of your research.

IT: I am interested in the left-right (LR) asymmetry that is seen in molecules, cells and organs of living organisms.

IK: By LR asymmetry of molecules, are you referring to molecular chirality, for example, seen in amino acids? That they are known to have L- or D-configurations, but they are almost exclusively found in L-configurations in living organisms?

TI: Yes. Since living organisms are made from these LR asymmetrical molecules, it should follow that cells are also LR asymmetrical. Further, I think that organs and bodies of living organisms are LR asymmetrical precisely because they are made from these LR asymmetrical cells, although this has not yet been fully verified.

Generally, I am interested in and researching the continuous biological organizational hierarchy, from the molecular to the individual body scale, as well as populations of individuals to the environment.

IK: Does LR asymmetry of organs refer to things like the heart being positioned on the left side (of the body)?

TI: Exactly and not only its position, but the shape of the heart is also LR asymmetrical. There are also people in this world whose hearts are positioned on the right side but are healthy. Some of these people have hearts that show LR reversal in shape, a mirror image of the shape seen in a normal body. Even with this reversal in shape, there may be no problems in function. The fact that the heart can still function even if there is a mirror-image reversal in shape indicates that the conventional heart shape that most people have was not necessarily selected for a functional reason. Just as the speed of light is simply fixed without a functional reason, once we are born onto this Earth, this is simply the shape we possess. It has no meaning. Yet the LR asymmetry is stereotypically fixed. It is this aspect that I find a certain beauty or romanticism.

IK: What led you to become interested in LR asymmetry?

TI: During my undergraduate and graduate school days, I was doing research on LR asymmetry in fruit flies in the laboratory of Professor Kenji Matsuno. Professor Matsuno’s lab conducts large-scale genetic screens in fruit flies from which they discovered various mutants exhibiting abnormalities in the LR asymmetric development of the intestine. And I was studying how the mutants showed such abnormalities. While we were able to publish papers from the lab, I was not entirely satisfied with the explanation.

IK: What was the explanation given?

TI: That the LR reversal of intestinal development was caused by the reversal of cell chirality states.

In addition to molecules such as amino acids, cells of the body are also known to display chirality. This is all well and good, but explaining the LR reversal of intestinal development is due to the reversal of cell chirality merely defers the actual issue. Unless we investigate why this reversal of cell chirality occurs or why organs can display LR reversal in the absence of cell chirality reversal, we don’t really have a complete explanation. Perhaps the reason I continue to pursue research on LR asymmetry is because I want to address that lingering doubt that I have for myself.

What happens when cells rotate?

IK: What kind of research have you been doing since coming to RIKEN?

TI: I am continuting to research LR asymmetry and am currently studying cell rotation. Caco-2 cells, which are epithelial cells, when viewed from above, are always seen to rotate in clockwise direction. They rotate approximately 50 degrees per hour. I am studying the rotation of these cells when they form multicellular colonies.

IK: If the cell rotates on its own, then it seems likely that they will also rotate when you have multiple cells.

TI: One would think so, right? But picture two gearwheels meshed together. If both of the gearwheels move in a clockwise direction, the gears would not rotate.

IK: Hmm... That's true!

TI: But cells can rotate collectively. They rotate about 10 degrees per hour. We are currently developing a model to understand the mechanims behind this collective rotation.

IK: How did you feel when you discovered the cells could rotate even in a group?

TI: I was ecstatic!

IK: Did you discover this collective rotation of cells using a special technique?

TI: No. I always try to adopt simple experimental techniques. I culture the cells and look at them closely and carefully. That's all. I am not employing any particularly special methods. If I had to pick something, I would say that I am particular about quantifying the process. I do not just want to describe what I see; I want to convert things that could only be expressed in words quantitatively. But even that does not require any particularly advanced techniques. I think it is cool to examine what anyone can see in ways no one has ever thought of before.

IK: So why do these cells rotate?

TI: I believe that there is no functional reason. We have a tendency to try and explain biological processes in terms of their function, but just like the speed of light is fixed, there is no meaning to it. There are cells that rotate. I want to view this simply as a physical constraint, with exactly the same significance as an apple falling to the ground. If there are cells that rotate, I want to explain their physical mechanism. I especially want to prove it not only theoretically, but also empirically.

I want to be a calm and composed scholar

IK: Lastly, could you tell me about your future aspirations? For example, what kind of researcher you'd like to become or your ambitions.

TI: Lately, I find myself thinking that I would like to be a scholar with a calm and composed demeanor.

Just as complaints like, "Young people these days are incompetant," have been heard since the Roman times, in academia, we often hear grievances that "there are more and more specialists and researchers today, but fewer scholars with a broader perspective." While I dislike that kind of condescending talk, at the same time, I find myself thinking, "Yeah, actually, I want to be a scholar."

I know it might sound like I am putting myself on a pedestal as I talk about this. But let me be clear, putting yourself on a pedestal is not a good thing. There are as many researchers as there are police officers in Japan, yet we do not seem relatable to most people. In fact, it's not just that we seem unrelatable; we may even be slightly disliked. I want to change that reality. I want people to see us more as equals.

IK: I thought that it was nice that the name of your favorite band was written in your researcher profile. It made you feel more relatable.

TI: I could probably go on for another hour just talking about Suzuki Mikiko Zu. They are a band that manages to find a balance between hardships and happy ending. Please give them a listen sometime.

IK: I want to find balance between hardships and happy endings. I'll give them a listen. Thank you for sharing so many different stories.