Research into bacterial virus protection systems has led to the development of CRISPR-Cas genome scissors, which have made Lithuanian researchers famous worldwide. “It shows how great the potential of this research is, how many undiscovered mechanisms of action there are, which may have many applications in biotechnology, molecular biology, industry and so on in the future,” says Mindaugas Zaremba, a researcher at the Institute of Biotechnology of Vilnius University's Life Sciences Center.
Dr Zaremba’s team will now try to determine not only how individual defence systems work, but also how they interact with each other. According to the researcher, this is a new level of research.
We talked to Dr Zaremba at the VU Life Sciences Center to find out more about bacterial research, the bureaucratic challenges faced by researchers in Lithuania, the importance of research communication, and why he chose to become a researcher.
Q: When did you realise you wanted to be a researcher?
A: Only in the 10th form. As I grew up, my perception of what a profession is changed a lot. When I was very young, I imagined I would be a millionaire (laughs). I just thought there was a profession to be a millionaire. Then, according to my father, I wanted to be a welder, a builder, and then a maths teacher.
I used to be very sick a lot, I had to interact a lot with doctors in hospitals, and I was still a good pupil, so my parents thought I should become a doctor. With that “programme” in mind, I studied, but eventually I became interested in chemistry. I had a very good teacher, and I took part in chemistry Olympiads... I had an older neighbour who was studying biochemistry, and I realised in the 10th form that medicine was not for me, so I chose biochemistry.
I was most interested in how nature works at the molecular level, how certain biological processes work, what mechanisms are involved. Since I was a child, I wanted to understand how things worked, down to the smallest detail. I used to love to dismantle various devices that I didn’t always manage to put back together (laughs).
Q: How interesting - often when you talk to researchers, it becomes clear how important teachers are. One teacher can have a very strong influence, as in your case.
A: Yes. It’s very important to get pupils interested and help them discover what they like. Then, once a pupil is interested, he or she will definitely make the effort, even move independently in the desired direction, to improve. And that can grow into something more - like in my case, becoming a researcher. I call such teachers “pupil entrepreneurs” - they can guide a pupil to where he or she is suited and enjoys it.
Q: You are now researching the resistance of bacteria to viruses. Why is this topic important?
A: Bacteria, like humans, are under constant attack by viruses (bacteriophages) - this happens all the time, so bacteria have evolved defence mechanisms against them over the course of their evolution. Otherwise, they would die out. At present, over 100 different bacterial defence systems have been identified, varying in both their structural organisation and their mechanisms of action, but only a small number of them have been studied in detail, and some of them have found wide practical applications.
Probably the best-known example is restriction-modification, which gave rise to restriction endonucleases, which initially revolutionised genetic engineering and more recently led to the discovery of genome scissors, CRISPR-Cas, for genome editing. It shows the great potential of this research and the many undiscovered mechanisms of action that could have many future applications in biotechnology, molecular biology, industry etc.
Bacteria used in industry are also bioreactors that produce certain substances in the pharmaceutical, chemical, biotechnology and food industries. It is therefore important to understand how to make a bacterium resistant to different viruses in order the processes (such as cheese or yoghurt production) could continue uninterrupted.
There are also bacteria that are resistant to all the antibiotics that have been developed and that know how to defend themselves. This is a global problem, and it is no longer cost-effective to develop new antibiotics. So alternatives are being sought. One of them is phage therapy, which has been around for more than 100 years. Bacteriophages are viruses that exclusively attack and kill bacteria. The aim of this therapy is to kill bacteria with viruses. But it has not been used in the past because antibiotics were cheap and effective. Now that the effectiveness of antibiotics is declining, attention is turning to phage therapy.
In short, we have bacteria that produce something for us that we want to protect. And bacteria that are dangerous to us, that we want to destroy. In both cases, it is therefore very important to identify how they interact with viruses, which can then be exploited.
Q: What are you and your team focusing on now?
A: Together with other colleagues in the Department, my team is researching different bacterial defence systems. We are mostly transferring these systems and monitoring their performance in the most studied E. coli bacteria. Recently, we have been working intensively on prokaryotic Argonaute proteins, which have been the subject of two publications in the prestigious journal Nature Microbiology last year.
We have also launched a project funded by the Lithuanian Research Council (LRC) to investigate different bacterial defence systems. Sometimes there can be dozens of these in a single bacterium. We will try to understand not only how these systems work individually, but also how they interact with each other within the same cell. This is a new level of research.
Q: Reading your biography and the list of research you have contributed to, it is obvious that you are very active and have been awarded the Lithuanian Science Prize. How would you name the main goal of your research?
A: My main goal is twofold. First of all, fundamental research, which is very interesting to me as a researcher. That is, to shout “Eureka! I’ve figured out how it works!” And then to put the systems I am studying into practice, for example, by developing new molecular biology tools or detection systems, such as the CRISPR-Cas nucleases involved in bacterial protection against viruses, which have been applied to genome editing and the detection of nucleic acids (such as the genetic material in the RNA of the SARS-CoV-2 virus).
Q: As you mentioned, you also work with CRISPR-Cas. This technology is, of course, also very controversial in society. Do you think it is possible to ensure the safe, ethical use of CRISPR-Cas and other powerful technologies, for example, in China, which is investing heavily in research and technology, but, as practice shows, is certainly not always following international agreements?
A: The use of any technology can be both good and bad. For example, nuclear energy, as a technology, is neither good nor bad. The question is what it is used for. If it is for electricity generation that is fine, but if it is for an atomic bomb? The same with CRISPR-Cas: it can help treat various genetic diseases, which is already in development. There may also be uses beyond ethical boundaries.
Because we do not yet know exactly what the consequences of CRISPR-Cas will be, and if we edit the human genome in such a way that it will be passed on to the next generation, we do not yet predict what will happen then. But it is being discussed, it is being tried to be agreed upon.
However, there is a grey area, where unethical researchers, I will call them, can opt out of the agreements and do their own thing. An example is in China, where a researcher edited the genomes of twins in violation of agreements and ethics to cure them of HIV infection, even though the twins had not yet contracted HIV. But then the researcher was condemned by China itself, convicted and sentenced to 3 years in prison.
I think, however, that you cannot control those who do not want to follow the rules, just like anywhere else.
Q: Has the perception of the profession of a researcher changed? What did you expect when you joined, and how do things look now that you’re doing research?
A: In fact, when I joined, I romanticised the researcher’s profession to some extent. I imagined that I would be delving into the mysteries of nature in some laboratory, mostly imagining myself alone.
Now that I am also a supervisor of PhD students, when I am managing projects, nuances have emerged that I never thought of. That is, communication with the team, attracting funding and the huge administrative burden of managing projects, a lot of “paperwork”, procurement challenges... The further you go, the more time it “eats up”. For me, it is a disappointment - it is not what I wanted. On the other hand, if I want to do research without having my own money, without being a millionaire, as I dreamt of being a child (laughs), it is not possible to avoid this in Lithuania.
Q: You mentioned the administrative burden. What other challenges do you face?
A: First of all, the funding of education in Lithuania is still very low. More precisely, it is half the EU average as a percentage of GDP. As far as I know, ministries are already planning for a significantly higher share of GDP to come from the development of high technology (including life sciences and biotechnology), so an increase in the funding of research, which is what generates high technology, is inevitable. Simply put, you cannot generate more value added if you feed the cow less but milk it more (laughs).
Of course, it is also very important that the funding is sustainable and stable, independent of European Union funding periods. It has happened before that funding ‘pits’, where, for several years in a row, there were simply no calls for proposals to carry out their research due to delays in EU money, have even led to some researchers leaving the Academy.
However, the situation is slowly improving, and the Ministry of Finance, together with the LRC, is working to prevent such pits from appearing. A new LRC Board has recently been approved, a new Chairman has been elected, and there are already signs of positive developments, such as increased funding for student research practice work. Once the new composition of the LRC research committees has been finalised, the research community is looking forward to new positive developments in research funding. We shall see how the future unfolds.
Q: What about public procurement? To be honest, I never thought that procurement could be such a big part of a researcher’s work.
A: As the person who manages the projects on whose success my future research career depends, I am the person who is first “hurt” if a project starts to stall. This can happen because of research uncertainty, which is beyond our control as researchers and cannot be predicted or controlled in advance. But it can also be due to more mundane things, such as not acquiring the necessary reagents or equipment fast enough to meet the needs of the project. And then there is the “realm” of public procurement, whose rigid and stringent rules are often incompatible with the unspecified and urgent acquisitions inherent in research.
Of course, I would like to express my sincere satisfaction that there is an initiative on the part of the decision-makers to make life easier for researchers, as a new version of the Public Procurement Law has entered into force since the beginning of this year, with changes that are important for research.
However, I would like to urge them not to stop there, but to continue to facilitate procurement for research and experimental development. In research, we are competing with the whole world. In the so-called “hot” area of research such as genome editing, there is fierce competition: whoever is first to carry out the research, whoever is first to publish it and patent it, will be the leader in the field and will be able to reap the sweet fruits of the new technologies created, establishing high-tech start-ups and high added-value jobs.
Q: In order to increase funding and make the public procurement system more user-friendly, it is important to have both political will and public opinion about research and researchers, because, after all, the money comes from the taxpayers. And that is where research communication comes in. How do you assess research communication in Lithuania? What do you do yourself to make communication between researchers and the public more effective?
A: A very fair question. I think that communication with the general public is becoming more and more mandatory. I am trying to be part of that. I am always happy to talk to children about DNA, and I am invited by various student organisations to present my research field.
The hardest thing is to talk about research to people who are not involved at all. It’s easiest to talk to colleagues and students (laughs). But you have to know how to talk to the general public. The improvisation training I have been doing for quite a long time at IMPRO GYM helps me. I’m learning how to speak in public, how to get my message across. Recently, I took part in the VU Innovation Department’s INNODAY event, where we have to present our innovations not only to the public, but also to business - what we have to offer, what we can offer. In a word, if I have time, I am always happy to talk. I would encourage other colleagues to do the same.
By the way, I think the importance of researchers in society was very much highlighted by the COVID-19 pandemic. The researchers of Vilnius University really played first fiddle in explaining what an infection is, how it spreads, what the myths are, how vaccines work, what their importance is and so on. It is very important to present research and evidence-based facts to the general public.
It seems to me that when society faces big challenges, researchers can always be called upon to offer real solutions. Of course, researchers are often not the ones who like to appear on the screen, some are very self-critical or think: “oh, no one will be interested in it”. Then they need to be ”interviewed”. That way, there will definitely be people who want to talk - like me, let’s say (laughs).
Q: It is very interesting that you mentioned the pandemic. Polls, public opinion surveys show that, not only during a pandemic, but in general, public confidence in researchers is growing. Which may seem strange, because a marginal group that is against practically all research-based information, especially in social networks, is very vocal. The impression is that there are a lot of them, but that is not the case. The vast majority of society does trust researchers.
A: I think that is the way it should be. Because real researchers can only speak the language of evidence. After all, there are also pseudo-researchers who are able to manipulate the public, and it may be in the interest of certain political forces to have such “loudmouths”.
People often ask what I think about certain events. If it is my area of expertise, I am always happy to share what I know. Ideally, people should not read Facebook posts, but ask an expert in the field. For example, with all due respect, a PhD in philology or a lawyer cannot comment expertly on how vaccines work. After all, these are different fields, and a doctorate does not mean that one is an expert in all fields and can be trusted.
It happens that the less an “expert” is knowledgeable in a particular field, the clearer things seem to him, the more confident and louder he is explaining things to others (laughs). However, only true experts in their field can give a full and correct account of an often ambiguous situation. That is why I wish the public would rely more on the opinions and recommendations of researchers who are experts in their field.
Q: Thank you for this interview.
A: Thank you!
Interviewed by Goda Raibytė-Aleksa