About bioinformatics – first-hand
"Bioinformatics is not just "put a computer on and count""
About naked diggers, scientific communicators and wet laboratories
Ekaterina Erokhina, Indicator
Candidate of Biological Sciences, member of the Faculty of Bioengineering and Bioinformatics of Lomonosov Moscow State University and the Institute of Bioorganic Chemistry of the Russian Academy of Sciences, as well as an active participant in the Moscow Science Slam and other projects of the Association Artur Zalevsky in an interview with Indicator.Ru spoke about the "sinusoids" in the career of a biologist, about the curse of "tyzhbioinformatics" and about the unrecognized frontiers of scientific pop in Russia.
– Bioinformatics is an interdisciplinary field that requires understanding both programming and biology. Who comes to it and how, and what was your experience?
– I got into bioinformatics completely by accident. At school, I wanted to create some kind of cyborgs, implantable implants, for example, chips that can be inserted into the head once and no longer memorize the rules of the Russian language, but immediately write without mistakes. Of course, my favorite science fiction pushed me to this. And at some point I found out that MSU has a faculty of bioengineering and bioinformatics. I had no one to consult on this topic, and I decided that I would study there. But when I entered, it turned out that in reality bioengineering today is basically genetic manipulation at best at the level of fairly simple organisms, such as E. coli or yeast. I was, of course, a little disappointed: I went to one place and ended up in another. But I liked it here in general.
In Russia, bioinformatics is understood as a rather narrow field, primarily related to the processing of genomic data, and the study of the structures of biological molecules. But in the world, it also includes a huge number of other areas related to the processing of any biological data using information technology. Therefore, physicists, mathematicians, chemists, people from related fields of biology, programmers in the broad sense of the word come to bioinformatics today. At the same time, professional knowledge in the field of biology is very important for bioinformatics: if you do not understand what biological task you are solving, what data and why you are analyzing, then you will get meaningless garbage at the output.
– But there is a division among bioinformatics, when some are more engaged in creating data analysis methods, while others apply these developments to a favorite biological problem?
– Absolutely. At any conference, a report can hook you either with a biological problem that you are interested in studying, for example, aging; or with a biological object that you also work with, say mice or C. elegans nematodes; or by the methods by which this object and problem are studied. And different groups act differently. Some were able to put their own unique biological model, they learned how to breed some animals better than anyone else and all sorts of methods are "incited" against them. For example, we have a colony of naked diggers at the faculty. And there are groups like us, rather with methodological competencies. We are able to model biological molecules using a different set of methods at scales from chemical reactions to the assembly of nanocontainers using DNA origami technologies. And people come to us with completely different biological objects and tasks that need a specific method. But often both directions are combined in the same group. That is, you have a certain main topic or task, and around it you are developing methods.
– And what has guided your work since you entered this scientific field – the development of methods or interest in a biological problem?
– A difficult question for me. My "childhood trauma", student and dissertation, is related to thrombin. It is a key protein in the blood clotting cascade, in principle, one of the most studied proteins in the world. But, surprisingly, several mysteries are still connected with it. I am dealing with one of these problems: for some reason, thrombin behaves differently depending on the presence of sodium ion. It would seem that sodium is always in our blood, but still the behavior of thrombin changes. I've been struggling with this for ten years now. We applied a variety of methods to thrombin, including our new technologies. For example, we have developed a pipeline for modeling chemical reactions; it uses, of course, the tools of other groups, but we have combined them with our own and now apply the same pipeline to other objects. For example, to enzymes that should prevent poisoning with chemical warfare agents. I gave up thrombin for a while, I was engaged in other tasks, because it is already impossible to work with it when the result is not obtained for so long. I managed to develop a method that allows us to study the interaction of combinatorial peptide libraries (peptides are short proteins consisting of three to four amino acids) with different biological molecules. And it turned out that I could apply this method to thrombin again, gain new knowledge, new hypotheses, which, apparently, are justified. It seems to me that many people move along the same sine wave: you have an object around which you are struggling, sooner or later you get distracted from it, work on new ideas, create new methods and return to it with them – and what if it gives up this time?
– Returning to bioinformatics as a field: there is an opinion that it is developing well in Russia, including because it does not require as much money as for the maintenance of experimental animals and other components of wet laboratories. Is this true, or is bioinformatics also a rather expensive field?
– I may be mistaken in the quote, but it seems that once Mikhail Gelfand and Konstantin Severinov even called (half jokingly, of course) to refuse to finance wet science in the Russian Federation – given how much reagents are coming to us, it's easier to invest all the money in bioinformatics and become leaders in it. It is difficult to comment on this because I do not know the exact cost of wet labs. In general, of course, computers are cheaper. But there is a downside, which, unfortunately, many speakers from the positions of "cheap bioinformatics" do not take into account. Bioinformatics is not just "put a computer on and count." Building a normal computing cluster, an infrastructure suitable for bioinformatics, is a separate difficult task. And its support also costs money: it is both repair and payment of employees, and such specialists are more expensive than in the usual technical support. And sometimes computers suddenly break down, big computers break down badly, they can be idle for weeks and months. At this time, the whole group of scientists is idle, but they still need to pay. And in order for the work to stop less, you need to invest more money in reservations, in qualified specialists… As a rule, when talking about "cheap bioinformatics", people do not take into account the real cost of computing infrastructure on which world-class research can be done. But the most important thing is not even that. Bioinformatics, no matter how you twist it, must operate with some kind of data. Of course, today there are open databases of biological data, but people from all over the world are already "grazing" on them, including a huge number of bioinformatics from India and China. Therefore, it is only on your own data that you can make high-quality science that will go to top magazines. And to get them, you need either well-tuned collaborations abroad, or your own experimental laboratories.
– And how is the process of obtaining your own data built? Which of the experimenters do you cooperate with?
– I will tell you about our computational biology group of the Faculty of Bioengineering and Bioinformatics. We have the closest possible collaboration with several laboratories at the Institute of Bioorganic Chemistry of Academicians Shemyakin and Ovchinnikov of the Russian Academy of Sciences, in particular with the groups of Ivan Smirnov and Alexander Gabibovich Gabibov. With them, we develop antidotes to chemical weapons, study the mechanisms of antibiotic resistance and its overcoming. They have huge competencies in high-performance wet methods, which allows them to accumulate a large amount of data. Together we publish high-quality articles, and in the future, I hope, we will get real products for the pharmaceutical market. Plus, we have collaborations with Sechenov University, in particular with the Institute of Molecular Medicine. There we also model molecules for colleagues, and they test them experimentally. And, of course, we have a lot of collaborations inside MSU. For example, I participate in the projects of Marina Borisovna Gottikh's group, which studies the human immunodeficiency virus. To successfully embed the virus into the genome, it uses some of our own cellular mechanisms, and now we are working on how it can be prevented from doing so. And we also have a number of applied projects. For example, for one small pharmaceutical startup, we also come up with molecules that, ideally, will help fight anxiety and depression. So we were lucky to form our own network of contacts with strong groups inside Russia, and through them we have connections with larger international collaborations. For example, one of our long-time colleagues works at the University of Aix-Marseille, and with him we are doing several projects to study the interaction of zinc with various proteins and aggregates, which is also important in some neurodegenerative diseases.
– Is bioinformatics evolving fast? You have named a lot of topics and directions. Is it typical for your field to increase the specialization of scientists?
– I really participate in very different projects, for example, once during a summer practice at the Belomorskaya Biological Station of Moscow State University, students and I discovered a new species of Arctic jellyfish. The authors of the article about this are all the students who participated in this group. There are projects related to the study of drugs, there are projects to study metabolic networks in which different substances inside our body are synthesized and disappear. I'm doing this precisely because I'm insanely interested in figuring out how everything works there. And this, of course, works against me. If I had concentrated on some tasks, I would probably have finished them much earlier, achieved success and would have moved more productively to the next ones. Practice shows that if you are not sprayed, you are more likely to reach some heights, get new biological knowledge. But still, many of my bioinformatics friends are jack–of-all-trades. I think the reason is that there are just very few of us. Despite the fact that now they seem to be talking about bioinformatics from all sides, even Rosneft is doing this, there are still not enough specialists. Both my colleagues and I are ready to be invited anywhere: "Count this for us, count that, you can, you're bioinformatics." And it doesn't matter that you are engaged in a completely different field. "Tyzhbioinformatik" is the same formula as "tyzhprogrammist, so fix my printer." I hope that with the help of our faculty, our graduates, there will be less and less such distraction.
– How has the pandemic affected your scientific work?
– For me personally – as disastrously as possible. Again, from the logic of "tyzhprogramist" in March, I was assigned the duties of deputy dean for distance learning of our faculty. We quickly deployed an online platform where classes are held and additional services, we support teachers and students, we try to smooth this process as much as possible and provide them with everything they need. Of course, it takes a lot of time, and I'm not actually doing anything in science right now. This is very disappointing, and I'm looking forward to the moment when at least the session ends and I can return to data analysis. Even now, at least in the evenings, I try to help my colleagues a little. In general, the work of the experimenters was stopped, and this is a big problem for our projects. As I have already said, our group always tries to work with experimental colleagues, because any of our predictions need to be validated experimentally, otherwise it's just computer games. Or we must rely on the most reasonable biological data: the more additional biological information that we can impose on our task as external constraints, the better the result, the more accurately it describes reality. Considering that the acquisition of these additional biological data has stopped, as well as the experimental verification of our hypotheses, we are also a little stuck now. We spent this time calculating new data, and as soon as everything is restored, we will immediately give out bundles of new hypotheses to our colleagues. Plus, we were engaged in improving our tools. And yet, like any normal group, we have accumulated a large amount of data, which we are slowly making out in manuscripts. During this time we have already sent two or three articles to the magazines.
– You were actively engaged in popularization before the pandemic and continue to perform online now. Has the audience's attitude to science changed during the pandemic?
– I prefer to call myself a scientific communicator rather than a popularizer, because scientific communication is a broader concept that includes communication with colleagues from different fields. But popularization in the sense of communication with the general public is also part of my role as a scientific communicator. Usually I tell first of all about my work and rarely about my field as a whole. And it's really hard for me to say whether the attitude has changed, because I initially work mainly with those audiences who are already interested in science. Some call it "preaching to the converted." Unlike my colleagues, from the same Alexander Panchin, I am not interested in fighting with fans of myths, there is enough of another headache. During the pandemic, the audience, of course, has changed a little due to the transition to online, and this is wonderful. At various events that I am currently attending as a lecturer and as a guest, I see a large number of people from the regions. As a rule, there are very few high-quality scientific pop activities in the regions – "Gutenberg's Smoking Room", FUNK, Geek Picnic and that's it, perhaps. And access in real time, not on the record, to events, to real communication is a positive feature of quarantine. Although, of course, communicating online with an audience is far from the same as having a live conversation.
– If debunking myths is not too interesting, what is your main motivation to engage in popularization?
– For me, this is the fulfillment of what can be called a social contract or a social contract. As a researcher, I work in a state institution, even in several, and most of my research is funded by state funding – it is either direct budget money or grants from state scientific funds. In reality, this is taxpayers' money. Accordingly, I feel responsible for these funds and believe that in return I should tell a wide audience where they are going. This is not spelled out anywhere, in very rare grants there is a condition to talk about what is being done in the project. But it is only in the Russian Scientific Foundation that I see that work is really underway to promote these results, and this, of course, is the merit of the wonderful press service of the foundation - Maria Mikhaleva, Yulia Shulyak and their colleagues. So, on the one hand, this is such an internal duty, but at the same time I just like to talk about my science. I spend most of my life on my work, and it's interesting for me to share this when people like to learn something new, when I see joy in the eyes of listeners from being told about something interesting. And of course, as a fan of my faculty, I consider popularization one of the tools to attract applicants to us.
– Do you think popularization works in this capacity as a direct tool of attraction? Is it possible to set the global task of popularization as follows: saturating society with popular science information, restoring the prestige of the scientist's profession and, as a result, attracting students to scientific and technical areas?
– It is possible or not, it no longer plays a special role, because this is how many colleagues, especially festival organizers, set their goals. In the installation documents, they prescribe this: "our goal is to increase the prestige of both technical and scientific specialties, attract new applicants," etc. Regarding whether this works or not, I will try to start from afar. I believe that it is still like walking to Beijing to get saturated with information about science, simply because a huge number of people in the regions are not yet covered by this communication. And in Moscow, the audience for popular science events is actually not that big either. Yes, when you are, let's call it that, in a "hangout", it feels like there are three or four parallel lectures going on somewhere every day, and you have to choose all the time where to go, where to listen to which friends. But in fact, a huge part of the audience is simply not covered yet, and not because people don't want it. My personal practice shows that they are always interested. Now, because of self-isolation, I travel a lot in a taxi, and when I leave work, drivers always ask: "From university?", we start talking about this, and there has never been anyone who would not be interested in learning about science. So there is a desire, but the lack of free time plays against people. For many families, survival is now, unfortunately, in the first place, and people simply do not have, say, the space of freedom in their heads for leisure. Online partially removes this problem. For example, at one time, with colleagues from the company Future Biotech, we made broadcasts to gaming services such as Twitch. People come there to watch gamers' streams, and see some kind of lecture nearby, come in to see what's so strange going on, and are really interested. Even such accidentally dropped by schoolchildren are interested in this, and it seems to me that everything also works to attract them. I think this is a giant channel both to attract applicants and to increase the popularity of the profession, which we are not using yet. And this is our gigantic problem, because in Russia people in general do not really understand what science is, what scientists do in general. As a person from a small industrial city, I myself, before entering the university, did not know at all how academic science works, why scientists need internships, what publications are. And impact factors, rating magazines, quartiles were generally concepts from another universe.
– So the efforts of popularizers now need to focus on capturing new sites?
– Representation, of course, needs to be increased. But in general, "need" is a bad word in this sense. Because at least in my environment, all colleagues and friends who are engaged in popularization do it just for fun. And for me, this motivation is also the main one. If I didn't get professional pleasure from the process, I certainly wouldn't be doing this. Of course, if under the conditions of grants they write to us "write a popular article", everyone will write, but what will come of it is another question. Good scientific communication, like any job, requires time, effort, and preparation. It is necessary to study the theoretical basis in this area, to understand what communication strategies there are, how, what and to whom it is worth telling, what techniques can be used, which ones should be refrained from, how to spread your knowledge across the audience, across sites. It is necessary to determine the formats and platforms that are convenient for you, because there are also many nuances here. I know a lot of wonderful lecturers who perform amazingly live, but if you put them in front of the camera with the same topic, you will not find a more depressing spectacle. And I believe that it is absolutely impossible to force people to engage in communications. You can encourage, attract, show what opportunities there are, give it a try. But it is impossible to force him to be a scientific communicator, this is a completely failed strategy.
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