Darja Klementová, who comes from an artistic family, studies clarinet at the P. Křížkovský High School in Brno, which specialises in artistic subjects. However, she has also been interested in nature and the human body since she was a child, so finally decided to devote herself fully to molecular biology, choosing to study at the laboratories of Masaryk University’s (MU) Faculty of Science. For her work, which deals with the role of kinases from the CK1 family in the Wnt/β-catenin cell signalling pathway, and the potential application of these findings in the treatment of leukaemia, she won the national ‘České hlavičky’ (Little Czech Mind) award.
As a high school student with an artistic background, how did you end up at the university laboratory?
My journey to the laboratory was a little different than usual. I was already interested in biology, and especially molecular and cellular biology, in my first year of high school, and I wanted to devote myself to this field, and push myself beyond the scope of regular teaching. At the age of 13, I signed up for the DNA Club course under the guidance of Marek Šebesta from CEITEC as part of the Bioskop project, which offers courses in biological sciences for primary and secondary school students at the MU Faculty of Science. That’s when I actually entered the university laboratory for the first time.
Did you find the work at the laboratory with Bioskop so interesting that you wanted to continue it?
At Bioskop, my future consultant, Marek Šebesta, approached me and offered me the opportunity to continue studying molecular biology and learn how to think scientifically. For the next two years, thanks to him, I visited various research groups and got to know the scientists, who showed me what they were working on.
What interested you the most?
The research team of Vítězslav Bryja, which is dedicated to the study and characterisation of signalling pathways inside cells. I found it interesting that knowledge about one specific enzyme needs to be placed into the broader context of a given signalling pathway for proper understanding. In essence, it is a complex network where many proteins interact with each other, and we are trying to figure out how and why these interactions occur and what effect this can have on a person, such as the development of cancer. In 2020, we agreed that my work would act as a kind of bridge between two research groups, namely Vítězslav Bryja’s laboratory at the MU Institute of Experimental Biology and that of Richard Štefl’s laboratory at CEITEC.
How did it go?
First, I had to create CK1α and CK1α-like kinases in Richard Štefl’s laboratory in order to examine them at a later stage. Kinases are enzymes that bind a phosphate group to their protein substrate, with subsequent effects on their overall properties. My goal was to find out which specific proteins from the Wnt/β-catenin signalling pathway are phosphorylated by the kinases under in vitro conditions. Having done this, I then analysed the kinases in the laboratory of Vítězslav Bryja under the guidance of one of his team members, Tomáš Gybel.
What did you find?
Previous studies have already shown how disruption of the CK1α kinase by mutations within the Wnt/β-catenin pathway can lead to the development of two serious haematological diseases, myelodysplastic syndrome and acute myeloid leukaemia. Any increase in our knowledge of CK1α, therefore, could prove really important for improving current treatments of these diseases, such as through the use of more precisely targeted CK1α kinase inhibitors.
In my study, I provided the first information on CK1α-like characteristics, something that had not previously been described in the professional literature. I compared the activity of the CK1α and CK1α-like kinases I obtained with their relative, in living cells. I found that, under in vitro conditions, all the kinases phosphorylated the same protein substrates, though this does not happen in reality. It follows, therefore, that the different substrate specificity of kinases in vivo is influenced by other, external influences, and not through properties of the kinases themselves.
That sounds like a pretty big task for a student who still has school to catch up on. How did you cope?
It helped me a lot that the teachers at the high school went out of their way to help me. I had an individual education plan, which allowed me to alternate work in the laboratory with school. It was a bit difficult at first as I wasn’t sure how to do some of the experiments myself and, for that reason, I was very much tied to the time options of my consultants in the laboratory. Now, after two years of laboratory work, I have gained experience and confidence, so I more able to manage my time on my own.
You are also studying clarinet playing. When do you find time to practice the clarinet?
It’s challenging, but I always try to find time to practice, especially when I have a concert. My other subjects are the same as a regular high school, so there is a lot to cope with. However, I have a lot of support from the teachers at the high school. The school itself is relatively small, so there is a great family atmosphere and everyone helps each other. Even so, from a time point of view, I sometimes get into problems. In short, sometimes things don’t go as planned in science and you have to repeat an experiment, sometimes several times in a row, before you achieve a successful result.
What was the reaction of the scientists at the university when they had to talk to a high school student?
It never found that someone looked down on me for not knowing something or not understanding something. It certainly helped that I’m not the first high school student to attend the university. Before I arrived, numerous high school students had already worked in the laboratories and achieved great success, and this motivated me a lot.
Will you continue in science? Where will you apply after graduation?
I definitely want to continue studying natural sciences. I am applying to study experimental and molecular biology, with a focus on molecular biology and genetics, at the MU Faculty of Science. I would like to finish my ongoing projects and turn the results into publications. I would also like to be there when a new inhibitor that specifically targets the CK1α kinase is being tested in our laboratory. This could potentially be used to treat some cases of myelodysplastic syndrome and acute myeloid leukaemia. In the future, I would like to gain further experience in molecular biology by studying abroad.
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