All of you could do a PhD at Stanford or MIT

This year, you started working on a project, Towards an atomic understanding of the first moments of a protein’s life, supported by the Czech Science Foundation (CSF). The catchy title caught my attention and is actually the reason why we chose you for the interview, though several other researchers from UCT Prague also received CSF funding.

When I talk about science, I make an effort and enjoy interpreting my findings in the form of stories. Our project is about researching ribosomes, something I’ve been working on for seven years. I like to personify them and often compare the functioning of ribosomes to human childbirth during lectures. Because it’s easier to imagine something as intrinsically human as childbirth than it is to conceptualize the Lennard-Jones potential, which describes the interactions between atoms. A few weeks ago, Professor Pavel Jungwirth received a grant from the European Research Council (ERC). He is going to study, in detail, the interactions between atoms and ions, and in all interviews, he uses the analogy of a beating human heart. He sees a connection between our heartbeats and some microscopic parameter for calcium ion. That’s great, isn’t it?

If a grant proposal has a catchy title and is written in an accessible way, do you think it has a better chance of getting funded?

From a personal point of view, it would be great if this were the case. But I haven’t written enough proposals to be able to answer this question based on statistics. Quantitative research has shown that the appearance of the first page of a proposal is important to reviewers in the grant application review process. So, in this case, I made the title and the opening page stand out. That said, another successful CSF proposal in which I was a co-investigator was just the opposite. In terms of graphics, it was so ugly that I wouldn’t want to evaluate it. But the proposal was funded (laughs – editor’s note).

Please elaborate on what you expect to encounter as you are proceeding with this project, in terms of understanding the birth of proteins.

Almost every protein in the world has formed some kind of ribosome. A ribosome is a 25 nm complex with about 50 molecules that catalyses a chemical reaction. Protein synthesis takes place by combining protein building blocks, amino acids. An unbranched chain is formed, which typically has around 300 amino acid residues. For the protein, getting out of the ribosome takes quite a long time, on the order of seconds. The protein therefore spends a non-negligible part of its life bound to a ribosome, like a child connected to its mother by the umbilical cord, to use the childbirth analogy. No one knows exactly what happens to the protein at this stage; it’s uncharted territory.

Why don’t we know anything about this process yet?

Current techniques, such as electron cryogenic microscopy or nuclear magnetic resonance spectroscopy, do not “see” the initial phase of protein birth. Accordingly, we only have structural experiments available for about ten different nascent proteins, which are very specific. We know almost nothing about the rest. I study nature using computer models, machine learning, and structural analysis, thanks to which we can “see” what an experiment cannot.

What is the basis for modelling something that cannot be seen?

We know what amino acids look like, how they join in a chain, and how the chain grows. We also know the physical laws of the microuniverse. We enter the information into a computer and use it to predict what’s happening inside a ribosome, for example, in a part that’s called the exit tunnel. There are some special constricted places that the protein has to pass through. We do not know how it moves through the constriction region, what force makes it to do so. We also not know why constriction exists in ribosomes at all. What purpose could it have, since evolution has not removed it in over hundreds of millions of years? There are biochemical experiments showing that without narrowing, ribosomes function poorly, making non-functional proteins or not making them at all. It is also interesting that a large class of antibiotics binds precisely to the constriction region, which adds overlap to the applied setting complementing our basic research activities.

I assume that modelling events at the atomic level would be very demanding in terms of computational power. Do you use computing supercentres, or do you make do with UCT Prague’s infrastructure?

We have been able to employ the largest machines in the world for quite some time now. When we do a molecular dynamics simulation of a ribosome and count about 2.5 million atoms and their interactions, we consume supercomputer computing time in the order of weeks. We use the computing centre in Ostrava and compete for time elsewhere. Just as an example, when I returned from Germany from the Max Planck Institute in 2018, I had 40 million core hours of computing time allocated for my project in Stuttgart. At that time, in the Czech Republic, the Ostrava supercomputer centre had just announced a competition with the capacity of 70 million core hours for the entire republic.

Is limited computing time limiting to you in your research?

I am more limited in my “real-world” time, because I also have to teach, have a family, and also commute quite far to UCT Prague. If I suddenly had access to a large computing resource, I would be under more pressure to use it. Calculations need to be well planned and phased.

You mentioned that the outputs of your project may have overlap to applied settings, to antibiotics development. Is potential use in medicine (and thus helping people) a motivating factor for you in being a scientist? Or do you just enjoy exploring the unknown, and when a discovery comes with real-world impact, it’s a nice bonus?

B is correct: I'm really interested in how things work and why they do what they do. I look at the world realistically and do not set unnecessarily large goals. I am not lying to anyone, not even to myself, that I will invent a new pharmaceutical. I don’t know, of course, if twenty years from now I might be disappointed by the fact that I spent my whole life tinkering with theoretical concepts and that you can’t buy anything I developed in a pharmacy. However, I do not share the current obsession funding agencies have, requiring basic research to be related to a social problem. After all, a lot of revolutionary and useful things have come about thanks to people digging into something that, at first glance, seemed useless.

I find your approach to basic research perfectly legitimate.

It is legitimate when we have fun together. But I can’t simply write to a funding agency that I’m interested in why there are suddenly five positively charged amino acids here in the ribosome and why evolution didn’t throw them away. That I don’t care whether an antibiotic is currently being attached to the site. But the funding agencies, in principle, require possible real-world applications. So I’m just going to tell them what they want to hear, because undoubtedly, there’s always some link to an antibiotic. But in the drug research field, an idea is often so far from implementation that it’s pointless to declare it.

At UCT Prague, you lead the Laboratory of Biomolecular Dynamics. How difficult was it to start this group?

Our group has been operating for six years now and the beginnings were hard for me. I had nothing to do with this university before coming here from Germany, and I think that UCT Prague is not very good at integrating scientists who did their training elsewhere. I see inbreeding being cultivated at every turn. To this day, I sometimes feel like a dissident who clearly has a different opinion than the people who studied at UCT Prague and straight away continued their academic careers here.

What did you struggle with the most?

I don’t list my daily frustrations (laughs). It has been time-consuming for me to find the necessary forms. I didn’t know how grant applications work at UCT Prague, who was in charge of which agenda, or how teaching works here. I often didn’t even know who to ask, and when I did ask, I usually didn’t get an answer. A lot of information is spread through grapevines among colleagues who spent their entire careers here and know how things work.

But enough criticizing: I was given space for absolute independence, and no one has told me what research topic to pursue and how, which has been fantastic. And some things are changing for the better. For example, getting the Project Centre going is a great step forward.

If you were to compare your time here with life at the Max Planck Institute, what do you miss the most?

Probably a way of thinking about science that I don’t see here. Here, we talk a lot about grants, administrative duties, and citations. But to talk to someone about ribosomes and proteins first and only later discuss about administrative tasks? I don’t experience that here, unlike in Germany.

Are you missing anything else?

Although I have been working at UCT Prague for over six years, I do not have any intensive cooperation with anyone else at the university. I’m certainly partly to blame for this; I don’t tend to actively reach out and try to convince others about things we might do. In Germany, we always had events where we could meet each other and solve purely scientific matters. For example, internal seminars, conferences, and thematic lectures, which many people attended. People were active, curious, and interested in learning how their colleagues could help them. A few days ago I was at a lecture on machine learning organized by the UNICORN association, and there were maybe ten, fifteen of us there.

Why do you think it’s like this?

The fact that the Institute of Organic Chemistry and Biochemistry AS CR (IOCB) is nearby might play a role, because a lot of high-quality/ambitious people do their doctorates there or work there. Many UCT Prague colleagues are strictly technologically oriented thus they do not crave scientific knowledge. I need people who enjoy learning about the workings of nature and are not scared of words such as derivation, optimization, or programming. In my opinion, UCT Prague does not target the best students in the given age cohort. When I teach sophomores, I ask them, for example, who will go to Stanford after they graduate? And they stare at me with surprise, wondering if I lost my marbles. Almost no one starts with an ambition to do a PhD at a top-ranked university. Then I tell them: you could all go to Stanford or MIT; people there usually don’t have better brains than you, they’re just dedicated to their interests and consider it normal—even in their free time!—to talk about science, learning, solving tasks together, and preparing for a scientific career.

Is there something in which, on the other hand, UCT Prague excels compared to institutions where you worked previously?

I really like the social activities organized by the university on the Dejvice campus. CrossCampus, Hanami, Campusfest. I also find the relationships between younger and older students that is visible, for example, with tutoring activities, to be great.

How do you feel about the possibility of going abroad again in the future?

Right now, the Czech Republic is the place where I want to live permanently, but I’ve not yet closed the door to future international chapters. If the opportunity presented itself and, above all, provided favourable conditions for my family, I would like to do more work outside the country. Let’s say, as part of a sabbatical, for example. I have a few places in mind where I’d love to collaborate with specific scientists for a longer period of time. But I also have three daughters and a wife, and each of them has interests and responsibilities here in the Czech Republic…it would not be easy to coordinate.

Do you have a scientific dream?

You just touched upon my soft spot. All great scientists say that you have to have big dreams and goals. I don’t have them. I’m a little sorry about this but it’s probably connected to my aforementioned realist outlook on life and my tendency to avoid disappointment. So I’m just gradually working my way through the laws of nature.

You are one of the few active Czech scientists on Twitter (@mhkoscience). What motivates you?

I was originally looking for doctoral candidates there. Now it’s a kind of hobby. In any case, science is a community affair, and if a person wants to be successful, he or she must be part of a scientific community. It rarely happens that a lone scientist suddenly comes up with a discovery that takes the whole world’s breath away. Rather, it is about small discoveries that the community gradually adopts and continues to refine. Without marketing, no one will know you’re around these days, so I’m tweeting.

You use a combination of bike and train to get to work from the countryside near Kolin.

I don’t like to drive, and traveling by train, in particular, is a special to me. It’s a time when I can think and feel good. I really enjoy train travel, even though I hardly travelled by train as a child. During my studies, I travelled along the Trans-Siberian Highway and in southern India. On the Beijing-Almaty-Moscow-Košice route, I returned to the Czech Republic by train after my friends and I decided to visit northern China and track Siberian tigers.

Did you succeed?

Fortunately, no. Plans are one thing, but when a person enters the forest and realizes that a 300-kilogram tiger might be waiting for them, it’s just not good (laughs).