Introduction

This article was originally published on our company’s note（Japanese only） in October 2024. To reach a wider audience, we are also reposting it here on our official tech blog. The content reflects the information available at the time of publication.
(All organizational names and job titles mentioned in the article are as of the time of the interview.)

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ーーFollowing our first interview with our CTO, Mr. Nakamura, this time we are interviewing Mr. Isozaki, our Principal Investigator (PI). Thank you very much for joining us today, Mr. Isozaki.
To begin, could you tell us how you came to join digzyme? During your student days, you moved from the Tokyo Institute of Technology to the doctoral program at Kyoto University, correct? And after that, you joined digzyme.

Yes. I actually left the doctoral program at Kyoto University before completion. When I returned to Tokyo afterward, I found out that our CEO, Naoki Watarai — who had been my senior by one year at Tokyo Tech — had just founded digzyme. I thought it sounded really interesting, so I reached out to him, and that was the beginning.

ーーBack in your Tokyo Tech days, what kind of relationship did you have with our CEO, Naoki Watarai?

I originally met Naoki Watarai back at Tokyo Tech, when we were both involved in iGEM.（※The International Genetically Engineered Machine Competition）

ーーiGEM！digzyme is also supporting it as a sponsor.

Yes. iGEM is the world’s largest synthetic biology competition, where even undergraduates can engage in realistic research activities without joining a lab. During iGEM, Watarai-san and I were on the same team representing Tokyo Tech. It was a small team of just three people, so we got along quite well from the start. I could already tell back then that Watarai-san was an incredibly powerful and remarkable person. Over time, I became convinced that 'if Watarai-san starts a company, it’s going to be something really interesting.'

At the time, my own field of study didn’t give me deep expertise in enzymes, so I wasn’t that knowledgeable about them yet. After returning to Tokyo, I spent a while working in technical sales at another company. But after a short period of side work, I eventually joined digzyme full-time.

In my technical sales role, I would explain the platform we were handling to customers, then bring the information back to the company and hand it over to the appropriate engineers. That itself is an important job, and in fact it’s a position that digzyme still needs. However, most of the work was focused on customer negotiations, and I had very little direct involvement with new technical developments. I sometimes felt a sense of powerlessness in that kind of bridging role.

That experience was very valuable in giving me a hands-on understanding of what technical sales is like. But as a researcher, I believe creativity comes from being able to set your own challenges and run toward your own goals. At digzyme, I felt I could do just that, which is why I decided to commit fully. And I’m really happy that I can actually work this way now. I get a great sense of accomplishment tackling daily challenges.

ーーI see. It’s great to hear that you’re moving in the direction you want, and I feel happy listening to that! Specifically, what kinds of tasks or aspects do you find particularly rewarding?

I develop analytical technologies every day to solve challenges in collaborative research and new business projects. What I find particularly rewarding is the part where we discuss how to effectively translate biological features into dry analysis and then actually test them in practice. Specifically, we take the 'abstract challenges' we receive from our clients and break them down into very detailed hypotheses about the biological characteristics — testing them in dry analysis, and eventually connecting them to wet experiments. We refer to this process as 'translating' the features.

The procedure usually starts by identifying which aspects of biological features are likely to contribute to the problem we want to solve. In dry analysis, we formulate hypotheses and analyze things like structural differences, patterns in temporary sequence motifs, or whether the protein can be expressed in a particular species. But it doesn’t stop there: we also validate these hypotheses in the lab through wet experiments, or, in the case of collaborative research, have our partners test them directly.

Whether it’s collaborative research or our own projects, we can perform the full cycle of hypothesis testing — in other words, we can actually prove the hypotheses we’ve worked hard to develop. That is what gives me the greatest sense of fulfillment.

At digzyme, DRY and WET are seamlessly connected. Because these two foundations are solidly in place, it makes for a really excellent environment.

ーーNow, Isozaki-san, you are well-versed in both DRY and WET approaches… In your daily work, are there moments when you feel that your past experiences have been particularly helpful?

Actually, when it comes to DRY, my experience as a student was really just as a user — I could use some commercial analysis tools a little bit. I wasn’t able to write code or anything like that…

ーーWow! I can’t believe it…!

That’s right. And on top of that, I didn’t really know the logic behind how DRY tools are made — I was really just ‘able to use them.’ So I don’t think you could have called me a ‘DRY person’ back then (laughs). I was mainly a WET person.

During my doctoral program, I went offshore and studied marine bacteria. My main work was WET, and I only used Linux a little as a supplementary tool.

I used techniques like RNA-Seq — one of the next-generation sequencing (NGS) methods, which allows comprehensive detection of gene expression, known as the 'transcriptome' — to estimate the infection targets of marine viruses based on their genomic genes.

ーーI see. How about during your master’s program?

Up until my master’s program, I didn’t even know Linux, and I only used Windows — basically just Excel (laughs). At that time, I was even further away from genomics. During my master’s, I worked on cancer models using mice: transplanting cancer cells into mice, collecting samples, preparing tumor sections — it was almost like craftsmanship — and observing them under the microscope. You could say it was somewhat similar to what a pathologist does with human samples.

However, as I started attending academic conferences, I realized that if I couldn’t do any DRY work at all, I wouldn’t be able to survive, whether in academia or in any other research role.

I think many people who specialize in WET share this feeling. Most of the current members at digzyme would probably say the same thing: 'If possible, I really want to learn this too.

ーーBeing able to understand both DRY and WET approaches seems to have a lot of advantages.

Yes. But often, it can feel like you’re just pending, not really sure what to do. That’s part of the reason I deliberately changed labs when moving from my master’s to my doctoral program. I moved to a lab where I could potentially work with both WET and DRY. That said, as I mentioned earlier, I was only using commercial tools at the time, so I hadn’t even touched Python in terms of coding until I joined digzyme.

At digzyme, I learned everything from Watarai-san and Nakamura-san. Back then, we would occasionally hold programming sessions at a certain family restaurant (laughs), where they’d give me homework and I’d gradually improve.

Interestingly, having WET experience actually benefits DRY development. Understanding how WET researchers feel when using DRY tools is really valuable. Since we’re here, I can also explain what it means to do something in DRY that’s normally done in WET. First of all, you obviously can’t perform the experimental part of WET in DRY. What you can do in DRY is the investigative part. For example, at digzyme, 'enzyme discovery' is exactly that. Deciding which sequences to propose for a given challenge is normally part of the broader 'researcher' role. But because digzyme has the two foundations of DRY and WET, this 'enzyme discovery' is handled by DRY specialists.

If you can automate and quickly judge what sequences are likely to be effective in DRY, experiments in WET can proceed immediately afterward, and the number of experiments can also be reduced — there are many benefits. The same applies to 'enzyme modification.' You can quickly see in DRY where modifications should be made. But originally, all of this is part of the broader 'researcher' role. So, having WET experience naturally contributes to DRY development.

ーーGot it! That makes sense, thanks.
Going back a bit, could you tell us more about your research on marine viruses during your PhD?

I’ve always wanted to study viruses that exist in unusual places, not just in the ocean. As I mentioned earlier, I chose a lab where I could also do some DRY work, which led me to the Marine Molecular Microbiology Lab.

The motivation for wanting to study viruses in unusual environments goes back to when I was in elementary school. At that time, there was a somewhat popular book called The FUTURE is WILD (by Dougal Dixon and John Adams, with contributions by Takayuki Matsui and Akiko Tsuchiya), which simulated what kinds of creatures might thrive on Earth after humanity is gone. The book included CGI depictions of fantastical future creatures, like giant squid that looked almost like elephants — it was really captivating.

I was also interested in paleontology books. In evolution, when you trace ancient organisms, they generally get smaller — starting from microbes and gradually getting bigger is quite different from the world we live in now. I found that monster-like, imaginative aspect really fun (laughs).

So, I could have gone into a field like 'extremophile microbiology,' but I was drawn to something a bit more unusual. For example, there’s a hypothesis that viruses might have contributed to the development of mammals. The genes responsible for forming the placenta are composed of retroviruses, and in fact, the reason this suddenly appeared can be explained by viral evolution. Studying particularly unusual viruses like these seemed fascinating, and that’s what influenced my choice of research direction.

ーーI’m also curious about what viruses really are — they’re quite fascinating. Now, changing the topic a bit, could you tell us about any challenges you’ve faced in your work so far?

The main challenge is translating the abstract requests from clients into 'analytical approaches that are both commercially valuable and feasible.' Often, clients don’t know how detailed their requests should be for digzyme, or they simply can’t specify the level of detail, which makes the requests quite abstract.

For example, they might say something like, 'We don’t even have a concrete chemical structure yet, but we want something with roughly these properties,' or, 'It would be great if the production of this current product could be increased — we’re not sure whether an enzyme can be used or not.' When addressing these kinds of requests, we have to compare conventional methods and competitors with digzyme’s unique technologies, assess whether we truly have an advantage, and also consider market fit and other perspectives. Turning all of this into a concrete analytical approach is a challenge each time.

As for how we overcome this, we resolve it by consulting the right people, both inside and outside the company, as early as possible. Also, now that the business team has grown, I’m less often involved in the initial client meetings, so I personally encounter these abstract requests less frequently. I’m grateful that, as a company, the layer that converts abstract challenges into concrete plans has been steadily strengthened.

ーーWith the team growing, it seems that the environment for solving challenges is steadily improving. By the way, speaking of 'consulting the right people inside and outside the company,' Isozaki-san, I get the impression that you communicate very actively within the company. I personally benefit from that all the time, but do you do the same externally as well?

Yes. For new business projects, I often interview experts using platforms like VisasQ. In particular, for topics related to the Food Business Division, we sometimes gather experts through Mr. Takuo Miyauchi (Director and CSMO) and get their insights.

ーーThat’s reassuring. Are there any insights from these interviews that have particularly stuck with you?

There are many, but as one example… When we asked whether it would be commercially viable if the activity of a certain enzyme (the kind used in tests) could be greatly increased, we received the following comment:

‘The activity of this enzyme has never increased beyond a certain point. Of course, if it could be increased, the accuracy of the tests would improve, which would be good… but I’ve never seen such a case from a technical standpoint.’

ーー‘I’ve never seen anything like that!’ — That must have been really thrilling!

Yes. I could confidently tell myself, ‘This will really hit the market.

ーーThank you for sharing such a wonderful example. I have a follow-up question: what principles or values do you prioritize in your work?

For me, it’s about keeping open communication both inside and outside the company. To achieve this, I focus on building relationships where it’s easy to consult each other early when problems arise.

When psychological barriers are low, it’s less likely for relationships to turn sour. I’m careful not to signal any ‘walls’ to others, because visible barriers can create an ‘us versus them’ mindset. As long as the relationship is at least neutral, it prevents unnecessary conflict and makes problems less likely to occur.

ーーThat’s quite moving. Speaking of Isozaki-san, what kind of challenges would you like to take on in the future?

What I am currently working on is the overall management of WET research operations.
In the past, employees were organized flatly under our CTO, Nakamura. However, starting this year, Takayama-san (PI = Principal Investigator, Hiroo Takayama) and I have taken on a layer above all WET members as PIs. Under us are the PMs (Project Managers), while DRY members report directly to Nakamura.

Since I’ve never directly managed the research work of WET members before, it has been a bit challenging. I am moving forward with support from Takayama-san, my fellow PI.

Looking ahead, I hope digzyme will strengthen its PM layer even further. Ideally, we want to increase the number of WET members who have some understanding of upstream (DRY) work.

That said, I realize that diving straight into DRY work can be confusing—people might not know exactly what to learn at first. That’s why I plan to convey this gradually through on-the-job training (OJT).

ーーI see. If the number of WET members capable of DRY analysis continues to grow, the organization will become even stronger. Are there any other challenges you would like to take on?

I want to promote the development of analysis pipelines that reflect the characteristics of enzyme families based on their three-dimensional structures. By doing so, we can tap into unmet needs across the enzyme industry and explore novel approaches that haven’t been tried before, which should lead to greater diversification and improved productivity in enzyme-based manufacturing. I hope to advance this together with Mr. Koichi Tamura, our informatics specialist.

digzyme’s strength lies in our ability to handle both upstream and downstream processes, while also preparing for production. This is fundamentally different from the nuance of “AI doing a bit of analysis for you.

ーーIt seems like this will become a move that truly leverages our strengths.

Yes. I think digzyme’s biggest distinguishing feature is that it’s deep tech with a genuine market-in mindset. In particular, all the executives naturally think in terms of scaling.
—Of course, the fact that we can differentiate ourselves in specific technologies comes from having professionals from various fields gathered here—but even putting aside whether it’s technically feasible right now, we have our antennas up for ideas that could significantly propel the business forward. That’s why we have this virtuous cycle: we can define the necessary technologies and reliably develop them.

In some cases, deep tech companies aren’t focused on scaling. But our philosophy is that a vague notion like “it’s fine as long as it makes some money” or “this technology is amazing, so surely everyone will want it” just won’t cut it. No matter how impressive a technology is, if it’s for applications people don’t actually want, it can easily end with a “Sure, it’s innovative, but…” and go nowhere.

Because we have a market-in mindset, we can truly move our customers. That’s why it’s so important to have people like Mr. Watarai leading the charge—investigating the cutting edge of business with scaling in mind, and translating those insights into precise technical language.

ーーFinally, could you share a few words for those future colleagues who are considering applying to digzyme?

We have a diverse team in terms of both personality and research or professional backgrounds, offering opportunities to gain experience across a wide range of fields beyond just research. So, if you’re eager to take on new challenges, you’re very welcome here!

▼Original Post［note（Japanese only）］
https://note.com/digzyme/n/n4cb24197110b