Dr. Miglė Tomkuvienė, PhD in Biochemistry, takes a different approach to our body: she studies what happens in genes at the molecular level. This research is long-standing, involving thousands of researchers around the world, and the results are extending the boundaries of human understanding. “Contributing new discoveries to humanity’s body of knowledge is the most important thing for me,” says the researcher, whose main research focuses on natural and synthetic modifications to DNA.
This year, Dr. Tomkuvienė was announced as the winner of the prestigious L'Oréal-UNESCO Young Talent Program For Women in Science. During the L'Oréal-sponsored project, she and her team will study one of the human proteins that silences the necessary genes. We talked to Dr. Tomkuvienė in her office at the Vilnius University Life Sciences Center (VU LSC) to find out more about the prize and the project, as well as Dr. Tomkuvienė’s other research and interests. She also shared longevity tips that she herself practices.
“For me, there is no such thing as a normal working day. But that’s the fun of being a researcher - we do different things every day [...] In my opinion, the more you do, the more you manage to do. I do a lot of things, but for me they are slow. Research is a long process, after all”, Dr. Tomkuvienė begins the interview.
Q: After school, you chose to study molecular biology. Why were you attracted to this particular science? And did you already know then that you would be a researcher?
A: When I was choosing what to study, I didn’t even think I would be a researcher. I didn’t have that phrase in my head... I chose to study a subject I was interested in, molecular biology. My choice was probably influenced by the researchers I met when I was still a schoolgirl.
Once professors Eugenijus Arvydas Janulaitis and Gervydas Dienys came to our school, and I was lucky enough to meet Prof. Saulius Klimašauskas. Also, when we were already in the grade 12, we went the whole class to the VU Institute of Biotechnology to try experiments with DNA. What and how the researchers told us really helped me decide what to study.
When I found out that there was a BSc program in Molecular Biology, I felt like a light bulb went off: yes, this is for me. Later, I chose Genetics for my Masters and Biochemistry for my PhD. I followed what I was interested in, what I wanted to learn.
During my studies, the interest remained, I started to practice in the laboratory, and slowly I got involved in research. That’s how I stayed (laughs).
Q: During the pandemic, you were one of the most visible researchers interacting with the media and the public. Did you feel a greater sense of communication within?
A: It didn’t add any extra meaning for me, because I still know that my main job is a silent one - to do experiments and research. In other words, what the public doesn’t see for years. When that research, usually combined with the results of many other researchers, is of direct benefit, all the contributing researchers are not named. Contributing new discoveries to humanity’s body of knowledge is what is most important to me. During the pandemic, the whole world was in a critical situation and communication was simply necessary.
My husband is a member of the Lithuanian Riflemen’s Union, and he has been telling me since 2014, when Russia took over part of Eastern Ukraine that if there anything happened, he would volunteer and go and fight. When the pandemic broke out, I realized that communicating with the public was my volunteering calling. So I saw my work in the pandemic more as volunteering to fight the virus.
Q: As far as I know, you are writing a popular science book on RNA. What kind of book is it and when will we be able to read it?
A: Yes, I am not writing it alone: we are six authors. The original idea was mine, but I knew I couldn’t write such a good book on my own, so I invited colleagues to join.
We are writing about RNA because RNA as a molecule was practically unmentioned and undiscussed before the pandemic. During the pandemic, there was talk about RNA vaccines and about RNA viruses. I was talking to journalists who kept asking me to tell them in two minutes what RNA is, how PCR tests work. I’ve been learning this for maybe 6 years, and suddenly I had to learn how to tell them about it in two minutes (laughs).
Obviously, a book is not going to replace interviews with journalists, but I want the public to understand better. So we are writing about the RNA molecule, what it does in humans and other animals, about viruses, about tests for viruses, and about gene scissors, because we also have the famous team of Prof. Virginijus Šikšnys at our center. It turns out that there is also a piece of RNA inside those scissors.
The book has already been written and we are editing it. We are waiting for beautiful illustrations. I hope it will be available for purchase soon.
Q: Today we are talking due to a very important occasion - you have been awarded the prestigious L'Oréal Prize For Women in Science. This prize is awarded for a year to carry out a specific study. Tell us more about your research that was awarded?
A: The Department I work in, led by Prof. Saulius Klimašauskas, at the Institute of Biotechnology at the VU LSC studies DNA modifications, which is one of the cornerstones of epigenetics. We study proteins that modify DNA: marking some genes in cells to make them work, and some - to make them ‘silent’. When cells differentiate, every human cell - tens of trillions of them - contains the same genome.
Humans, and other animals and plants, develop from a primordial cell that contains the entire genome. Cells divide, all share the same genome, but humans, for example, end up with different organs.
This is achieved through epigenetic processes. Some genes that are not needed by heart cells, for example, are silenced. One of the mechanisms for this silencing is DNA modifications. And these are carried out by special proteins we use. In a project supported by L'Oréal, we will study in detail one of the human proteins that silences the necessary genes as cells differentiate.
We are currently collaborating with geneticists at the VU Hospital Santaros Klinikos. Geneticists study patients with genetic disorders at the macro level. And we are trying to find out how things are happening at the molecular level, how the genes are dysregulated.
I hope that this will continue to be one of my main themes in my career. There are more than one of those epigenetic regulators, those proteins in the cell. So we will study one now and then move on to the others. And the network of known regulators is growing and growing.
Q: Did you have any idea that this year’s prize would be awarded to you?
A: Actually, I was hopeful, because after the pandemic, my CV was filled with all the items that are important for the prize. I also received support from my colleagues, especially when they told me that they believed in me. So I thought it was quite possible, but still... that phone call to tell me I had won was really very emotional.
Q: How else do you think the prize is important? Apart from empowering women researchers to do their research?
A: Not only do women winners get support for their research, but they also get a lot of support for publicizing their discoveries and ideas. It sets an example for the younger generation of what it means to be a researcher. Invite them not to be afraid of the exact sciences and to join in the research.
I will go back to communicating with pupils, and I will pay tribute. Just as I was once shown how interesting the field of research is, I will communicate with pupils. One of the conditions of the prize is to communicate with schools. I may even go to schools to tell them about my research and my career as a researcher.
Q: You conducted a study with the aforementioned Prof. Saulius Klimašauskas and colleagues, and discovered the so-called “designer nucleosome”. What is this nucleosome and why did you come up with this name?
A: It’s a catchy name to attract attention (laughs). It was actually a biotechnology project, because Prof. Klimašauskas’ team has been studying unnatural gene modifications for many years. So with the L'Oréal Prize, we will be studying natural gene modifications, and the “designer nucleosome” is unnatural. It allows us to manipulate DNA in the way we want to manipulate it for biotechnological purposes - that is, to create molecular tools which give us and other scientists around the world more opportunities to study DNA in different ways. After more in-depth research, such molecular tools could in the future be applied to medical diagnostics or therapies.
We have found that one of these synthetic modifications leads to very strong nucleosome twisting. Nucleosomes are DNA wrapped around a coil of proteins. Just as we wind threads into a spool, our DNA molecule is very similarly wound up in the cell on a special protein.
Our DNA is very long. About two meters in each cell. If it were just loose, it would get tangled up and might not even fit into the cell’s nucleus (where the DNA is). That’s why our DNA is twisted inside cells.
The synthetic modification we have created causes the modified DNA to twist very strongly. We used the word “designer” because we can put that twist on whatever DNA we want.
Q: And what does that twist do?
A: Naturally, in cells, it, first of all, packs the DNA molecule, as I said. It also regulates gene activity. For example, heart cells do not need the genes necessary for the brain, so those genes are very heavily twisted and sort of backed into a corner. That is the natural composition. And where we put our modifications, the DNA is very heavily twisted synthetically. So we decide where the nucleosomes are going to go, we are the designers.
Q: Because this is basic research, it will have to continue until it is applied in practice at some point in the future. Are you continuing your research or have you already passed on the baton to fellow researchers around the world?
A: We are continuing our own intensive research. We are now trying to fine-tune the twist even more, to see what else it can deliver in a biotechnological sense. In other words, what aspects of gene activity can we selectively regulate when we twist nucleosomes like this. We have published the original discovery itself in the full public domain, accessible to researchers around the world. Perhaps someone will have some ideas on how else it can be used.
Q: You have already mentioned a little bit about epigenetics, one of your research interests. I know that you are also interested in longevity. So can you tell us what epigenetics and longevity have in common?
A: Epigenetics regulates gene activity. If all our genes are working as they should, everything is in harmony, we are healthy and young. As the body ages, the regulation of genes gets out of sync. Cells start to malfunction, sometimes even turning on genes that are not needed. This, at the genetic level, eventually unbalances the body. If a large proportion of the cells in an organ are malfunctioning, then the organ is also malfunctioning. And if the whole body is out of balance, we start aging.
The breakdown occurs over time and is also influenced by environmental influences, resulting in the so-called “epigenetic scars”. This means that environmental exposures damage the DNA, where epigenetic markers may no longer be present. For example, UV light can damage the DNA in our cells. This can lead to mutations - changes in the DNA code.
Fortunately, we have special proteins that ‘maintain’ our DNA and repair the damage that occurs. They do a good job of this, and most of the time, no mistakes are left in the DNA. However, when damage occurs and the DNA repair machine is working at the site, epigenetic information is removed (as a side effect of the work done to allow the machine to reach the damaged DNA site), which may not be restored to the way it was afterwards.
This is very similar to conventional scarring: the skin at the site of a deep wound is restored, but it is not the same as it was.
When such epigenetic changes accumulate in large numbers, the regulation of cellular activity is disrupted, and this is the molecular mechanism of our ageing process.
Q: Longevity is now one of the most popular topics in both society and science. Do you think it is possible to stop or even “cure” ageing? Considering that, many researchers in the field regard ageing as a disease. And sooner or later, we figure out how to cure diseases.
A: I think that modern scientific knowledge already allows us to hypothesize that we may be able to stop ageing. I do not want to say to stop it completely, because maybe there are some aspects that we do not know yet. But there are certainly ways of slowing down ageing that are being explored.
We already know the molecular mechanisms. Once we know the mechanism in detail, we can come up with interventions to stop it. Amazing research is already going on, and when it is finished, it will be possible, for example, to propose the application of iRNA technology to therapies to stop the ageing process. In this case, the iRNA molecules would deliver proteins to the cell that would rejuvenate it and repair the dysregulated genes.
The research is still ongoing, but there are already promising results in studies on mice and monkeys. I look forward to the clinical trials.
Q: And what do you do yourself to keep your genes as harmonious as possible and to maintain the best possible health for as long as possible?
A: It is estimated that a healthy lifestyle can give a person about 15 years. These are not extra years - we simply live as long as we are meant to by protecting our bodies. If we damage our bodies, and I’m not just talking about smoking or drinking alcohol, but also poor diet, low levels of physical activity, it takes away the 15 years that we have, let’s say, programmed into our genes.
By taking care of ourselves, we can simply keep those years. And then, with new therapies developed by science and medicine, we may be able to extend our lives even longer.
I myself follow the basic rules to keep the 15 years I have (laughs). I am very conscious of my sleeping pattern, I sleep for 6–8 hours, I don’t use an alarm clock. It may be unexpected for some, but I try very hard to make sure that all the necessary sleep cycles are completed and that the brain’s recovery and cleansing processes take place.
I try eating a lot of vegetables. Although it is not my field, I am in contact with researchers in different fields and I heard this advice from a microbiome researcher at a conference that you should sample at least 30 different plants a week. It’s a fun game in the summer, although it will be difficult in the winter. Physical activity and at least 7 000 steps a day. I think these are the basics. I don’t do drastic experiments with my body.
Q: Thank you for your helpful advice and interesting answers!
A: Thank you.
Interviewed by Goda Raibytė-Aleksa
Photo credits: Justinas Auškelis