I was literally thrilled
with protein engineering
Mgr. Martin Toul
RECETOX, Faculty of Science, Masaryk University
Martin Toul graduated with a Bachelor’s and Master’s degree in Biochemistry from the Faculty of Science at Masaryk University. He is continuing his Doctoral studies at the same faculty in the Molecular and Cellular Biology and Genetics program. He works at the Loschmidt laboratory of protein engineering, where he deals with detailed transit kinetics of proteins, and is a member of the International Clinical Research Centre of the University Hospital of St. Ann’s in Brno (FNUSA-ICRC). Last year, he completed an internship in Thailand and his results have so far been awarded with the Brno Ph.D. Talent and the Rector’s Award for outstanding Master’s students. He will now enrich his successful scientific career with a four-month research stay at the University of Texas in Austin (USA), for which he managed to obtain a prestigious Fulbright scholarship. Martin is 26 years old and his hobbies include programming, floorball, working out and snowboarding; he also enjoys reading books by Stephen King and constructing origami.
What path led you to the field of biochemistry?
To be honest, I didn't enjoy biology at first, but thanks to my older sister I've been interested in chemistry since about the second grade. I learned the names of the elements, filled in their marks in crossword puzzles and I was looking forward to having it as a subject. Then I participated successfully in various Olympics, not only chemical but also mathematical and physical. However, chemistry has always led, so even at the turn of primary and secondary school I was clear that I would like to study it at university as well. Biology came more from a practical point of view, because I see greater potential in connecting the sciences with living nature. While it is true that I have never been very interested in certain aspects of biology, such as monitoring the anatomical features of individual animals or their systematics, I really ‘found myself’ when I examined the microworld, i.e. when working at the level of biomolecules, DNA and proteins.
What led you to choose the Faculty of Science at MU?
I liked the Bohunice University Campus. As I come from a small village in the Boskovice region, transport accessibility was also a factor. Furthermore, I knew that they certainly did not lag behind other science faculties in our country. Now, in retrospect, I'm very happy for my choice, especially when I see how well research is undertaken here, we even have a connection with CEITEC. I would say that, in the field of research, we often go beyond other universities.
What possibilities are there for involving students in practical research?
As for possibilities in general, there are many at the MU Faculty of Science, it just depends what you are looking for. Students from Brno in particular can devote themselves to SOČ. We have a number of high school students in our research group who are engaged in really interesting research, something I personally never dreamed of at that age.
As for studying at university, everyone must complete their laboratory studies module. If you want, you can start researching for a Bachelor’s thesis from the first year. In some fields, laboratory work is not a condition but in biochemistry, for example, the practical part of the Bachelor’s thesis is common. I personally got into research at the end of my sophomore year, precisely because of my Bachelor’s thesis. At that time, I was most attracted to organic chemistry, which is why I started to focus on organic synthesis at our Institute of Organic Chemistry. After about half a year, however, I felt that I was just suggesting chemical reactions on paper and I began to find the laboratory work in this field a little too monotonous, so I started looking around.
And then you started working at the prestigious Loschmidt Laboratory of Protein Engineering at the Department of Experimental Biology, Faculty of Science, MU. How difficult was your journey there?
Paradoxically, I did not realize how prestigious they were at the time. I remembered that we had had a lecture with Prof. Damborsky, who introduced us to what the Loschmidt Laboratories were doing; and I was definitely excited about the topic of protein engineering. Based on this, I wrote an e-mail stating that I would like to work for them, after which I was asked to send them a brief CV and cover letter in English. Subsequently, I was invited for a personal interview, where I met with the leaders of various teams. Based on a personal meeting in the laboratory, they selected what I could do and they immediately chose a project that matched my profile.
Generally speaking, what do you do in the Loschmidt laboratories?
At the Loschmidt Laboratories, we focus on protein engineering, which means that we modify a specific protein (or proteins) to exhibit improved properties, whether it is higher activity or longer stability, or we get rid of some undesirable side effects. In practice, such proteins can be used as medicaments, for the removal of waste and pollutants from the environment or for bioproduction of commercially important chemicals, vitamins and other substances.
What exactly do you deal with?
I specifically deal with detailed transit kinetics, which entails the detailed study of such proteins. In contrast to classic kinetics, which is dealt with by most other “protein” research groups, I study the reaction of enzymes over short time-scales, i.e. in the order of micro- and milliseconds. This time window contains the most information on mechanisms of enzyme behaviour and, as such, the data obtained provides much more information about exactly how enzymes work at the molecular level. Further, if we know the mechanisms, then we also know how to modify enzymes because we know exactly what their biggest weaknesses are. As a result, enzyme modifications are really targeted and not “blind”, as is often the case with the classic approach. This is important for both basic and applied research.
Specifically, I touch on both of these areas. I deal with luciferase, an enzyme that produces light. It is of great importance wherever we want to observe an otherwise “invisible” biological process using a light signal (even in a clinic). At the same time, however, this protein has a very atypical evolutionary history; thus, it can help us better understand how modern specialised biomolecules evolved from their ancestors. In addition, I also work with a tissue plasminogen activator, a clinically approved drug that helps dissolve blood clots. It is used to treat heart attacks or strokes, but unfortunately it does not always work as intended. We are looking at how to adjust this drug so that the treatment is more effective and the negative side effects are minimised.
You have completed the second year of your Doctoral studies. How much time do you spend studying and how much in research?
At this stage of my studies, I already spend most of my time in the laboratory, so I have one or two exams per semester. Plus, part of the study is conditioned by the teaching of younger students, so I help with leading practical exercises in bioinformatics and molecular biotechnology in the Loschmidt laboratories. In addition, we have a mentoring system for younger colleagues; so, for example, we Doctoral students teach students within SOČ. In general, I probably spend a little more time at work, but I think it’s a big part of science and the desire for knowledge so, as long as the research fulfils me, I'm completely satisfied.
Have you already used the opportunity to study or work abroad?
In the first year of my follow-on Master’s degree, I went to Sweden as part of the Erasmus programme. I have always liked Sweden as a country and I was attracted to Swedish culture. I wanted to combine my stay with something useful so we came to an agreement with our friendly scientific group in Sweden that I could join them for an internship, which I combined with studying abroad.
Last autumn, I was on my second internship in Thailand. Actually, I got there a bit accidentally. The Thai research group first came to us to share in our experience. During this time, however, we found out that we were working on similar projects and that I could use their know-how and instrumentation regarding kinetics.
What has been most beneficial for you on internships abroad so far?
In Sweden, I was also enriched by the teaching style, which was perfectly set up in the sense that it forced students to think more rather than simply memorising. One good example is "every answer in this test is correct if you justify it correctly". One simply finds out that it can work differently, one can get the good out of every way and try to implement it here, and thus improve the operation of the laboratory. We are very open to such changes and improvements.
You have now received a prestigious Fulbright scholarship, for which I congratulate you from the bottom of my heart. Due to the situation with the COVID-19 pandemic, your trip was unfortunately moved forward a year, but fortunately not cancelled. So you will now have an internship in Austin, Texas; have you always wanted to go to the USA?
From a travel point of view, the USA, and America as a continent, has always attracted me, both because the people there have a completely different mentality and there are lots of interesting places. However, as far as this specific stay is concerned, the main motivation was to spend time in the laboratory of one of the greatest experts in transit kinetics in the world, Prof. Kenneth A. Johnson, who works at the University of Austin. My main goal is to learn something from him and transfer the acquired know-how back to our research group. In fact, it closes a kind of cycle; I first collected data here, then more data in Thailand, and now it is necessary to interpret the large amount of data correctly and add the last piece to the whole puzzle. Hence, now is the right time to go to the United States and to analyse this data in detail with the help of Prof. Johnson. The opportunity to travel and get to know the culture of the USA is just the icing on the cake, a way of perfectly combining work and personal interests.
How difficult was the path to obtaining a Fulbright scholarship? How long in advance did you have to apply for a scholarship and how did the selection rounds go?
I originally tried to reach the deadline at the end of September 2019, so I dealt with everything during last year’s holidays. Unfortunately, at that time it was not mentioned anywhere that the selection rounds would be in October, at whichtime I was in Thailand, so I could not participate. However, I managed to arrange that my application was postponed to the deadline at the end of February; both of these deadlines were aimed at selecting applicants for the next academic year, i.e. 2020/2021.
So at the beginning of the summer, we started to arrange things so that I could apply for the scholarship and I started to find out what was needed. I even called their office once, which I definitely recommend because they always try to find satisfactory answers and clarify all ambiguities. I then started securing all the administrative documents such as transcripts or copies of diplomas. The most important and time-consuming were the two main documents. The first concerned my personal approach to science and the reason why I wanted to go to the University of Austin, while the second concerned a description of the project I wanted to complete there. In the end, I had to get three letters of recommendation, one from Professors Zbyněk Prokop and Jiří Damborský, my mentors from the Loschmidt Laboratory, the second from the head of my research in Sweden and the third from Prof. Robert Mikulík from the ICRC, who sponsors research on strokes.
The candidates were selected on the basis of all these documents, and I must say I was pleased that, unlike other competitions, this was not so bureaucratic; rather, it seemed to me to be based much more on “common sense” thinking. The Commission did not try to exclude applications simply because someone used a different font size on the form, and it was really clear that they sat down and read all the documents in order to assess whether the project was meaningful and motivated. The most suitable candidates were then invited to a second personal interview in Prague. There, it was clear that each member of the commission knew exactly what my project was about, which pleased me. Within about two weeks, I knew the final result.
What would you say to other students who are considering a Fulbright scholarship but find it unreachable?
They should definitely try it because it’s worth it. The selection process is definitely not about boxing or testing, so they don't have to worry about not having a chance to get a scholarship. The Commission mainly wants to see interest and enthusiasm, so if you have a goal and you think that a foreign trip makes sense, then you definitely have a chance. The main thing is not to be afraid and go for it.
What are your plans for the future?
I would like to stay in science. After my Doctorate, I want to apply for a postdoctoral position abroad again because I can see for myself that internships abroad are beneficial. One thinks that science has to be done in the same place everywhere, but then suddenly one sees that there is another view. However, I would not want to live abroad all my life, so in about five or ten years I would definitely like to be back in the Czech Republic, settled on the campus of some university. But who knows, maybe I'll join a biotech company.
Thank you for the interview and I wish you much success in your personal life and future scientific research.
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