— My first question is pretty standard. Where did you study and how did you get into biology?
— That'll take me a while to answer. You see, until my very high school graduation, I was a fully-fledged physicist who won academic contests. I graduated from Lyceum №131 , a physics and mathematics school in Kazan, the best school in the city and very well-known in Russia. And I was absolutely certain that I would pursue astrophysics. I had made this decision around the age of four and it never changed. Although, my father, a physicist as well, had the misfortune (and still does) of being an avid hiker. Surrounded by physicists, I traveled extensively throughout Russia. At some point, I became fascinated with invertebrate zoology, and in the tenth grade, I announced that I would study it. This was because on one of our hikes, I saw a huge variety of insects swarm a recently deceased lizard. I was so impressed that when I got back, I bought a book by Jean-Henri Fabre, read about wasps, and declared, "Guys, physics isn't for me. I'm going to study invertebrates." I graduated from Kazan University as a biologist, and I still work there.

— How did you transition from invertebrate zoology to molecular biology?
— Well, it's not the only unusual thing to have happened in my life...

— Let me tell you a secret. Everyone I interview has a rather unusual story. The previous invertebrate zoologist we spoke with, Alexander Tzetlin, also graduated from a physics and math school.
— My mother dreamed that I would pursue biomedical studies, but I decided to study invertebrate zoology instead. In the crime-ridden Kazan of the 1990s, studying invertebrates seemed ridiculous. I mean, butterflies and wasps? Really? But I promised myself and my parents that neither of us would regret it. From my first year, I started visiting the Kazan University's biological station on Sredny Island in the White Sea as part of a student construction brigade. As a result, all my work was related to marine biology, even though I was based in Kazan, in the middle of Russia. I decided to pursue marine biology with all my might. So I went, as they say today, "googling", which was to “to the library” back then. I picked up a dusty abstract journal and started looking to see who else in the world was studying the crayfish and crabs I was interested in. I found a Japanese professor, wrote an actual letter, sent it, and received a reply. We started corresponding. I received a scholarship from the Japanese government. And the competition was huge by the way, only few people in Russia received the scholarship each year. I came to Japan, and successfully defended my PhD thesis on marine biology with elements of genetics.
My thesis told a fascinating story about crabs that live in the hills and travel for several days to reach the sea at high tide at night and lay their eggs, from which little crabs immediately hatch and disperse. The process is synchronous, and these crabs are terrestrial. My job was to figure out what mysterious substance was providing that synchrony.
In my final year of graduate school in Japan, I met an eccentric scientist who said, "To avoid any doubts about what to do, you need to explain it to others." And I found it difficult to explain why I was studying those crabs and who would benefit from it. He also thought it right to focus one's efforts on something very outstanding and very unusual. He said that he was studying a recently discovered mosquito, the strangest one in the world. So I asked — and it was a pivotal moment — if I could join him in his fascinating mosquito research. Since then, I have dedicated myself fully to genetics.

— I'm confused. If you were planning to be an astrophysicist, and your mother wanted you to be a biomedical scientist, then invertebrate zoology is certainly a good compromise, but it doesn't quite fit into the narrative.
— I'm very lucky to have amazing parents. During my transition from physics to invertebrate zoology, I was all over the place. For a long time, I had poisonous tarantulas, thirty hamsters, not to mention other animals living under the same roof with me. But my parents had a great strategy. They believed that if a child, who is already quite grown up, wants to try something, it's better not to interfere. It worked out wonderfully.

— Isn't it possible to talk about synchronous crabs as a part of an amazing biology that you're doing? I mean, it’s great. Even your voice changed. "The crabs descend from the hill at night..."
— It's a very interesting topic and a unique phenomenon, but it's still hard to explain. When I said "there's this protease that is secreted by the mother-crab and signals to the little crabs it's time to dig because they will soon be in the water, and they need to break through the eggshell and swim away within 30 seconds", and people asked me then why a normal person would need to know that, I had no answer.

— Did you study in Japan in Japanese or in English?
— I have a natural aptitude for languages. I'm not particularly diligent, it's just a feature I have. I actually enjoy mirroring people, which is probably why I managed to survive in Japan. It was the year 2000. When we arrived in Japan, we were supposed to take a language course. I tried preparing myself in advance by learning the Japanese alphabet, 28 katakana characters, and could already write my name. We were told to form two groups: beginners and advanced learners. One of my colleagues, a Mexican, had been studying Japanese intensively for about five years and was immediately placed in the advanced group. He was bored being alone, so they put me in this group as well because I knew how to write my name. Everything was in Japanese, including the textbooks. I always proudly say that I was second in our group in written Japanese and first in spoken Japanese, but I don't mention that there were only two of us.
Before going to Japan, I read books that said you would never be able to fully blend in and would always be a gaijin, a foreigner. So I decided to prove them wrong and become a real Japanese person. In my opinion, people who come to Japan go through four main stages of acceptance. At first you think, "Wow! It's amazing! Everyone is so nice. Everyone bows. They have everything. They even have iced lemon tea. Life is perfect!" Then you realize that the country is completely different. You are truly an outsider. Nothing makes sense. And you say, "Okay, I'll try to become as Japanese as possible. I'll learn Japanese. I'll follow all these rules..."

— Excuse me for interrupting. What do you do with a million Japanese particles they use to sound polite? And how do you use verbs correctly? Can you instinctively tell which particle to use when conversing with a specific individual?
— I have some understanding of it. I fall in the top 5% of foreigners who can speak Japanese, even when it comes to politeness. Because in Japanese, you can offend someone by simply using an incorrect form of politeness when saying "thank you very much". My Japanese isn't perfect. There is still room for improvement. At some point, I decided to strive to become a real Japanese person. Then you encounter the final barrier as you realize that you don't quite understand that country, meaning that you'll always remain a foreigner. This is a crucial moment. Out of the 50 people who came to Japan with me to study, everyone left. No one stayed in Japan. You've done it all. You speak fluent Japanese. You understand the culture. However, Japan will never become your second home. There is no rectifying this. You'll always be an outsider. Hence, when I land at Sheremetyevo, I feel like I'm back in my homeland. I understand this country. I understand its people. In Japan, I'm always a visitor. A very welcomed visitor, being a professor at a Japanese university. But still a visitor.

— Do the Japanese understand that a foreigner might make mistakes?
— Absolutely. They understand it perfectly. Keigo, the polite form of Japanese language, is very hard to learn. Actually, with me it's often the other way around. I speak Japanese at a proficient level, and Japanese people often can't believe that I'm saying exactly what I want to say. Because they don't expect a foreigner to be so fluent. If you speak politely, the Japanese assume that you, as a foreigner, can't really know the true meaning of those words, and attempt to guess what you're actually trying to say.

— So they make a correction where it's unnecessary, based on a stereotype.
— Yes. For instance, when a cashier at a store asks if you want a receipt, the Japanese don't say no. They say thank you, which means no. It's a special form of reply. And when I say thank you, the Japanese think, "Alright, he's a foreigner. Here is your receipt, just as you requested." This happens all the time. You can't hide your appearance.

— How similar is the Japanese approach to science to that in Europe?
— Japan is going out of its way to make foreigners comfortable. For instance, my wife speaks Russian, and her Japanese isn't very good, but she manages well because all the document forms are available in English. She goes to the municipality and almost through gestures tells them that she doesn't understand anything, and they do everything for her there. In this regard, Japan is making significant efforts to assist foreigners, but up to a certain extent — you can be a great professor, but you'll never be at the forefront of Japanese science.
When it comes to science, Japan has taught me one thing, to avoid arguments. If a Russian or American scientist hears something absurd, we express our indignation. For the Japanese — it's commonplace, so everyone probably knows this — it's crucial not to offend someone's feelings. Even when you're hearing absolute nonsense, you first say, "Hmm... I didn't know that. I'll go read up on it," just to avoid offending that person. Because they might be genuinely mistaken. Their life may be depending on it. Say something wrong to them, like "homeopathy doesn't work", and they might jump off the ninth floor upon learning this terrible secret. Therefore, in Japan, everything is geared towards maintaining one's reputation and saving the other person's face. It really affects things.

— Now I understand why you're so successful at Kazan University.
— Oh, that's a good one. But it's true. I believe I have a much higher threshold for losing my temper, swearing, or engaging in destructive actions than many people do. It's not always a good thing, but it's certainly a reflection of the Japanese lifestyle.

— You're talking about the style of communication, but I was asking more about the learning style. For example, in Russia, we have scientific schools of sorts — it's a bit less apparent these days, but still — there is a sensei and students, and then one of the students becomes the head of the school themselves. They may have disputes along the way, and that's already a major tragedy. And then there is the American way, where you get your Master's degree in one place and your PhD in another, followed by a couple of postdocs. If you spend your entire life at one university, it means there is something wrong with you.
— I understood your question right away. It's just that it's difficult for me to answer it, and I'll explain why now. You see, when I arrived in Japan, this style, with a sensei and senpai, was in full swing. What I appreciate about it is the work in the lab is organized with succession in mind, with young scientists guided by more experienced ones. The older ones have their own teachers — they’re called not "sensei" but "senpai", meaning someone who is older than you. They teach you to ensure succession. In such a system, professors can be kings and gods. But even now, this leads to a vast number of nervous breakdowns in Japan because they can't express their negativity directly. That was the situation in 2000. Today, Japan is trying to emulate the American work style as much as possible, and there are now unspoken rules — perhaps even explicit rules — stating that to secure a good position in Japan, you must leave the lab you worked in and spend several years abroad. All the leading scientists, whether at RIKEN, Kyoto University, or Tokyo University, have followed this pattern. So, staying forever in your scientific “home-school”, progressing from student to researcher to head of the department, is no longer the thing in Japan. Entire new ecosystems are being formed, like OIST, the Okinawa Institute of Science and Technology, which was built on a mountainside. There, the situation is similar to the one in Europe. RIKEN, where I'm currently working part-time, has this cyclicality, with an anticipated five-year or six-year cycle. Japan is trying to catch up with the States, but it seems to have started a bit late and is, of course, lagging behind.

— If you work part-time at RIKEN, then what's your primary employment?
— I've actually been promoted. I'm now a professor at the Faculty of Medicine in the very heart of Japan, at Juntendo University. I'm practically a biomedical scientist now, just as my mother secretly wanted.

— Is she still alive?
— She passed away suddenly three years ago when me and my father were in Japan. I almost made it home in time, but alas. It was my first year of work.

— Let's get back to the topic of the mosquito. You said you spoke to the professor... Kikawada, right?
— I actually spoke to his superior, Takashi Okuda. He is an excellent scientist and a wonderful person. He was working on an unrelated topic when he came upon a book saying that 40 years ago a scientist named Vanderplank in Nigeria described a phenomenon where he poured water on mud and had that mentioned mosquito emerge from it. Okuda-san made a mental note of it, realized that there were no other such peculiar mosquitoes, and went to Nigeria, amidst looting and terrorism, to find that mosquito. He then spent a decade breeding a colony in his lab, right under his desk, while at the same time focusing on his main task of studying agricultural pests. The moment he established the colony, everything took off. I was lucky enough to get involved when the genetics of this mosquito were still unexplored. Only its physiology was known, and the movement towards genetics had just begun. Meanwhile, the remarkable Kikawada, who at the time was what you'd call a mid-tier researcher, was against Okuda-san introducing an unknown Russian into the team. He was questioning the need for more personnel when funding was not unlimited. Eventually, Kikawada and I became best buddies, forming a rather unique and rock-solid Russian-Japanese friendship. We've been advancing this field ever since.

— Just to clarify, by "this field" you mean molecular biology and genetics of various extreme organisms. What do you now tell people when they ask you why you're doing this?
— I came up with a fantastic example just this year. You won't believe how simple it is. I used to call it the preservation technology of the future and something that would help us when refrigerators failed. I'd say that it was extremely fascinating and so on. But since last year, I've had a rock-solid explanation. The COVID-19 pandemic is actually to thank for it because at airports, when you land and want to get a PCR test right on the spot, they perform an express PCR, which is pricier but quicker. You’ve probably seen these red counters at Sheremetyevo airport for taking the test. And it just so happens that the cells of our mosquito are used to produce the necessary enzymes for the test, namely polymerase and reverse transcriptase. They are so low-maintenance that we decided to try expressing recombinant proteins in them, and it worked wonderfully.

— So the cell line has turned out to be technologically efficient.
— It has turned out to be resistant to side effects. Usually when you express something inside a cell, everything gets messed up and doesn't fold properly...

— What about the crabs?
— The thing is, I worked with my crabs in a physiology and zoology lab that mainly focused on ecology. When I decided to start doing genetics there, I had to start from scratch. The challenge with the crabs was to get them, you had to drive for hours, crawl around mountains with a flashlight, and wait for them to show up. And to collect biological samples for later analysis on HPLC to see what proteins were there or for genetics, you had to spend several nights running around with a flashlight...

— Meanwhile, the professor had already brought all the mosquitoes from Nigeria and developed the line...
— Yes. With the crabs, I eventually found myself trying to balance the effort and potential outcome.

— You can have an excellent research subject, but it can be too complex to work with for various reasons.
— Exactly. We're still learning from our mistakes in this regard. We have a project about dormouse hibernation and an article about the dormouse genome coming soon, but it turns out that having an interesting phenomenon isn't enough. When we have to purchase those dormice in Volgograd, they are heterogeneous. They are caught in the forest and brought to us. It's unclear how to keep them. There is no genome [sequenced] and no methodology on how to work with them. It's quite challenging. But everything fell into place perfectly with the mosquito.

— This, however, leads to everyone being stuck with a handful of model subjects that are easy to work with and that everyone is used to, and we end up with a rather skewed view of biology. In older studies, the creatures were quite diverse.
— You've just highlighted probably the biggest conflict. Note that our lab in Kazan is called "Extreme Biology", and we're trying to maintain that balance. That is, we study very unusual phenomena and try to do it on most suitable subjects such as the spiny mice, our mosquito, the indestructible leech... This seems to be where the super abilities of the subject meet the applicable methodology. And, of course, NGS [next-generation sequencing] and genomic studies have been a great help to us. For us, it was nothing short of a revolution.

— Was it difficult to set up a lab in Kazan?
— It's still quite challenging. I've honestly been working for both countries my entire life. My Japanese lab has an official connection with Russia. Leveraging the authority of the Japanese side, starting with the partnership between Kazan University and RIKEN, and now Kazan University and Juntendo, has added reputational weight at times. For the first 15 years of my work at Kazan University, when I was studying and working in Japan, it was somewhat under the radar. At some point, the head of Tatarstan visited RIKEN, and we discussed everything with him. Also, the university competitiveness project 5–100 was launched back then. That's how our lab in Kazan was established.

— Just on a technical note, Russian experimentalists often complain about things being inconvenient, kits getting delayed, antibodies going bad because they have been taken out of the refrigerator at customs, and so on...
— There is a simple explanation. We all have used a single technology, high-throughput sequencing, and have been utilizing it for everything until recently.

— Sequencing in Russia is twice as expensive as in any other place.
— That's true. But once again, the Russian-Japanese partnership comes to our rescue. Kikawada’s side deals with in-vitro and in-vivo, such as cellular work and creating recombinant lines. We therefore focus on NGS and bioinformatics. That's how we've combined our efforts.

— So you do the simpler and more technology-intensive stuff here and the more delicate tasks that require better logistics are performed in Japan.
— Here's the most surprising thing.  When you get to know how it all works in Japan, you suddenly realize that the procurement systems are the same. So why does it take half a year in our country and less than a week in Japan?

— On the other hand, if you consider the logic behind a Mercedes, you'll find it to be the same as the logic behind a Zhiguli. Four wheels, a steering wheel, a carburetor...
— That was a real eye-opener for me. Advance delivery, commercial offers, contract, bidding — everything is just like in Russia. But somehow, it's still a Mercedes versus a Zaporozhets. Nevertheless, we are making progress. Just this year, we began to evolve towards becoming a comprehensive facility. I'm not entirely sure we will succeed, but we have started trying to stablish the technology for validation in Kazan, in situ hybridization involving morphologists and histologists. Here too, of course, we can't do without international partners such as Igor Adameyko and Petya Kharchenko...

— You have good partners. With collaborators like that....
— We're trying. It's challenging because the people from our lab get a taste of good collaborations and all strive to go to Skoltech and other places. They continue to work with us, but forming a strong lab in the Russian region is certainly very difficult.

— The problem is not that they leave but that they don't come back. On the other hand, it creates a network of collaborations for you.
— Absolutely. Again, it's my Japanese heritage. I try to never spoil my relationships with my alumni...

— So, there is this remarkable mosquito that, as it turns out, holds significant economic value. There are dormice that are fascinating because they hibernate, but they are a challenge to work with. Anything else?
— Let me tell you all the secrets, then. We're gradually becoming wiser, but there is always a certain balance between marginality and potential. One of our favorite subjects is this indestructible leech I’ve mentioned. It was discovered purely by accident when one of our Japanese colleagues, a turtle expert, pulled a five-year-old frozen turtle from deep freeze. Although the turtle was dead, a leech on it came back to life and started crawling towards the door. It turned out that a species of leech from the Ozobranchus genus, native to the subtropics, can withstand instant freezing without any preparation, unlike mosquitoes, which require preparation before they can survive desiccation.

— Is this some kind of side effect? What purpose would this ability serve in the tropics?
— Of course, it's entirely non-adaptive.
Another extreme organism that we are particularly fond of is the chicken. There is a phenomenon widely utilized in agriculture known as temperature torpor. The idea is the development of a chicken embryo can be slowed down by a slight change in temperature. Lowering the temperature by five degrees halts embryogenesis, but warming up the egg after a couple of weeks restarts the process.

— I can see how this could be marketed to the agricultural sector.
— Indeed. It turns out that this is an entirely unexplored area, despite its extensive use in agriculture. Synchronizing the hatching of broilers is a common practice, but no one really understands how it works. I can tell you, though, the acidity of the environment, which is indirectly altered by temperature, has a significant impact. It seems to be one of the fundamental laws of nature that embryogenesis and the development of various organisms are regulated by the acidity and alkalinity of the environment.

— Is it true for all birds?
— It's true even for reptiles, as temperature synchronization is crucial for simultaneous hatching of offspring. Temperature torpor has been known for a long time, but no one has really delved into it. It appears that we were among the first to examine it from a genetic standpoint.

— What about reptiles whose sex is determined by temperature?
— That's a slightly different phenomenon. From what I recall from literature reviews, their sex is determined by minor temperature fluctuations. However, it takes a more significant change in temperature to go into torpor.

— Does that mean that after torpor they will all be of the same sex?
— The thing is, during torpor, we observe a significant slowdown of all genetic processes. Perhaps a slight drop in temperature triggers a different mechanism.

— One of those mechanisms relies on drastic temperature changes, and it's responsible for synchronization. The other mechanism depends on subtle temperature changes and is responsible for determining sex. If these processes aren't separated by time, how can they coexist?
— That's a good question. I don't know. In chickens, we observe that a decrease in temperature doesn't inhibit the transcription machinery but rather redirects it towards rejuvenation. During torpor, transcription factors that are characteristic of earlier stages of embryogenesis are activated. Next in our "zoo" we have the entire range of Chironomidae. Our indestructible dry mosquito is, of course, the champion, but there are also Chironomidae that live in super saline lakes, super acidic lakes, and super alkaline lakes, often inhabiting places where other invertebrates simply can't survive. In super saline lakes with the highest salinity, the entire lake bed is covered with Chironomidae larvae, and nothing else can be visually detected.
A fascinating subject that we're still trying to get closer to are flies that feed on the surface of oil and asphalt lakes. They eat whoever gets stuck there and gradually fill their entire digestive system with oil, and they're perfectly fine.

— Have you tried examining the gut microbiome of these flies?
— No, we haven't been able to do that yet. You see, we have more subjects than opportunities to study them.

— It would be interesting to compare it to the microbiome of oil.
— Indeed. That's our dream. Both genetics and the microbiome are very intriguing.
And finally, our latest hot topic (or hot subject in this case) is the spiny mouse. I'm not sure if we'll be able to outdo our foreign competitors, but I hope so. Spiny mice can regenerate and restore up to 70% of their skin lost from their body without any scarring. They have spines on their back like a hedgehog, hence they're called spiny mice. Their primary defense mechanism against predators, however, is to leave their fur and skin in the predator's mouth and escape. You can strip off three quarters of a spiny mouse's skin, and it will regenerate without leaving any scars.

— No bacterial infection as well?
— None. And it happens because as we know from our observations and articles, these mice have a unique immune system where immune activation occurs in a distinctive way. Also it's not only their skin... We've noticed that they have somehow learned to regenerate their severed ears. Last fall, we traveled all over Russia, buying these mice from breeders for 100 rubles each, and established a colony in Kazan. People asked us, "Are you buying them to feed snakes?" And we replied, "No, it's for important scientific research." So now we have a colony of spiny mice in Kazan.

— What will you do when you run out of interesting animals?
— That's not going to happen. Our wish list keeps growing. I think it was Tzetlin who said in an interview that zoologists have been sidelined and that evolutionary research is now conducted using entirely different methods. However, I disagree. It's actually the opposite. We now come to zoologists and say, "Have you seen anything unusual during your field trips?" Igor Adameyko is about to publish a great article on serotonin control during development. Zoologists who observed that different populations of voles migrate differently helped him get well published. Zoologists are becoming the key players. Sequencing can now be done anywhere, but the question is what to sequence and where to look. Our list is actually growing, so I'm not worried. We have an abundance of subjects for now.

— On the other hand, the mechanisms are always different, and as soon as you move from a purely descriptive level, even genomic, to a molecular mechanistic level, things become incredibly complex.
— That's correct. During our joint work on the mosquito, we did the bioinformatics in half a year and then spent two and a half years contemplating it just to verify a single good prediction. Another initiative of ours is to establish a center for single-cell sequencing in Kazan. The approach that worked with the mosquito will work well here, starting with comparative genomics. We conduct experiments simultaneously on regular mice and spiny mice and analyze the differences. Our chicken project has suddenly found a strong Japanese collaborator who studies the hibernation of the African medaka (killifish). It seems that similar mechanisms are at play there, including control of developmental dynamics through acidity levels and involvement of autophagy. We're now combining studies on chickens and fish into a single project.

— If this is common in fish and birds, then it's likely common in all vertebrates, right?
— We need to investigate this a bit more.