How does Gabriel Demo leave and come back home all at once?

Joining CEITEC MU in 2020 as the group leader of Structural Biology of Coupled Transcription-Translation, Gabriel Demo is no stranger to Brno: he spent all his university years at Masaryk University. After postdoc position in the US, this feels like coming back home to him. But at the same time, he is switching his research field from chemistry to structural biology. How does he deal with leaving and returning to familiarity?

Let us go back to your childhood. How did you first discover your interest in science?

Since I was little, I have always been the type of kid who liked to read encyclopedias. That is when my interest in science took shape. When I entered high school, I discovered my strengths in math, biology and chemistry.

Throughout those years, I developed a particular passion in chemistry, which is why I then told myself, “Hey, let’s try for a school that offers programs in chemistry.” Which is how I became a bachelor student in general chemistry at Masaryk University.

On your way to becoming a science student, did you encounter any encouragement or difficulty?

When I was at that young age, I was not thinking about difficulties. However, I did receive many encouragements. My parents inspired me a lot. We spent a lot of time together during my childhood: we read the encyclopedia; my father and I played chess together; we also went hiking a lot. These experiences all helped to form my interest in science.

During my grammar school and high school years, there were science teachers who also offered me much support on the way to pursue my science education.

Please briefly describe your research area and current projects?

Initially, I studied chemistry: general chemistry as a bachelor student, inorganic chemistry as a master student, and biomolecular chemistry as a PhD.

Nevertheless, throughout all these years, I had always been interested and in touch with structural biology, which is my research area right now. My current projects focus on the transcription-translation coupling.

DNA is the genetic blueprint for producing protein, and RNA is the message carrier. During the transcription stage, RNA polymerases use a DNA strand as a template, producing an RNA strand. Then, in translation, ribosomes are the builders that connect amino acids into proteins, following the RNA strand's sequences. These two processes had always been thought to be independent of each other.

What we are looking at are the ways these two processes physically couple in bacterial cells, and how coupling may possibly impact viruses when they infect human cells.

Why are you primarily interested in transcription-translation coupling?

The idea that transcription and translation may be physically coupled was presented only about 50 years ago. In biology, we always think of these two processes separately, either physically separated by membranes in eukaryotes, or by highly packed genomes in bacterial cells surrounded by cytoplasm. Nobody investigated the details until recent years, so it remains a relatively unknown area.

We hypothesise that transcription-translation coupling could be a standard control mechanism, where the transcription and translation can regulate each other.

This can be crucial to understand the fast response of bacterial cells in a stress-inducing environment, while selectively producing only life-essential proteins. Transcription-translation coupling can be a mechanism fundamental for the survival of these cells, which will require more studies into the matter.

How do you think the research of transcription-translation coupling can benefit public health?

There are two different ways to look at this question.

Firstly, transcription-translation coupling might be connected to how these cells adapt to specific stresses. This knowledge can then be used to search for stress responses in eukaryotic cells, such as the heat shock response and its regulation, and in turn, to find out how to treat dysregulated responses, which can be very useful for treatments of cancer and neurodegenerative diseases.

Secondly, the coupling can be vital to how viruses replicate in human cells. Certain types of viruses, namely some specific groups of double-stranded DNA viruses (e.g. pox family), infect human cells into the cytoplasm.

It was shown that in the late stages of viral infection, these viruses are creating so-called “viral factories”, which include the host’s ribosomes. We want to see if these viruses can physically couple their viral transcription towards the host’s translation. If they do, then we can design some anti-viral drugs to inhibit the spread of viral infection throughout these cells.

Do you have an analogy to summarise your work?

We are looking at two supposedly separated large biological machines: the RNA polymerase and the ribosome.

We want to figure out if they can interact together as a super machine. We aim to point out the structure of this super system

Knowing the existence of an interaction between the two machines, now it is possible to imagine them co-working in cells, in the term of a ribosome-RNA polymerase super complex, which is also our target of research.

In the past, it was challenging to study the structure of this super complex, as it is highly dynamic. Now, with the recent technological boom in cryo-electron microscopy (cryo-EM), this task is finally feasible. Which is why, lately, the field of transcription-translation coupling has become popular, and I know of four or five groups that are also looking into it.

Can you share a turning point or defining moment in your work as a scientist?

I think the turning point was during my PhD years at Masaryk University. I was in the Glycobiochemistry research group led by Prof. Michaela Wimmerová, which at that time was a big group consisted of about 20 people.

It was like a family, we talked, and we went out together. Having such a great environment helped me figure out that I genuinely love my job and my research area, which in turn was my motivation to become a postdoctoral researcher in the US, paving the path to leading a research group that deals with the research topics I am most intrigued by.

You were a postdoctoral researcher in the US for 5 years. Were there any experiences encountered that you found helpful here working in CEITEC?

While working in the US, I learned how to write scientific papers. Also, my PI at that time was fantastic, he always made time for me when I wanted to meet with him, and we would often have long discussions that were very helpful. This is one of the experiences which I want to transfer to my lab - excellent communication.

My postdoctoral stay in the US also showed me how to properly run my lab. During those years, I gained valuable scientific experiences in the field of translation, which prepared me in setting up a well-established lab, thus helping me in avoiding the confusion from changing my field completely.

You joined CEITEC MU as a research group leader in 2020. What are some challenges or engaging experiences you face when setting up your research group?

One of the challenge or difficulty is that, when many of the scientists come back from the postdoctoral positions abroad, they are tempted to compare the systems abroad with that in CEITEC MU or in the Czech Republic as a whole.

Here is what I learned, don’t do any comparisons! And here’s why. From one institute to another, the procedure of setting up your lab can differ significantly.

For example, here in Czech Republic, when you set up your lab you build up everything from square one as compared to the US, where the lab has already been partially set up as a part of the starting package.

I also must adjust my mentality. As a postdoc abroad, I did not have to deal with tasks such as hiring people, writing the grant and meeting with the administration. I have much more responsibilities now. It is very challenging to find a balance between all these tasks.

Interviewing candidates is the most difficult task for me. I find it necessary to search for people with not only suitable CVs but also suitable personalities so that the lab can feel like a family to everyone.

Therefore, I must learn not only how to lead the conversation, but also to ask the most precise questions. My performances during the first few interviews were admittedly not great. But over time, I figured out that the keys are to draft the interview questions thoroughly and to have the candidates prepare presentations on their scientific achievements.

After all that, I can take a step back and observe the candidates: do they have a friendly personality that is right for a group working environment? Are their scientific experiences sufficient? And, the most important of all, do they express joy in their voice as they talk about science?

Moreover, when I was a postdoc, I worked by myself. But now, I ought to train myself to trust the people I hire to work with. It is necessary not to be in control all the time, to let others do a great job, as every person is different. The key here is good communication - I hope to create a lab environment where everyone is believed in, and not to be afraid to talk about problems at work or in personal life. I want to have time for every single member of my lab.

What do you do in your free time to relax from your work?

Growing up in Slovakia, I was surrounded by beautiful mountains, where I fell in love with hiking.

I also enjoy listening to jazz music, especially when I come home from work in the evenings. Living by myself, I always look forward to spending time with my family. Having my brother living close by in Brno means we can hang out quite often. I also make sure to visit my parents and relatives regularly.

Not to mention my friends in Brno, many of whom I know from my student years when living in dorms. It is relaxing to have friends that you can talk to for hours.

Interviewed by Sophia Man

Publication date: 30.04.2020