The Foundation for Polish Science (FNP) celebrates its 25th anniversary this year. To mark the occasion, we have invited 25 beneficiaries of our programmes to tell us about how they “practise” science. What fascinates them? What is so exciting, compelling and important in their particular field that they have decided to devote a major part of their lives to it? How does one achieve success?
The interviewees are researchers representing many very different fields, at different stages of their scientific careers, with diverse experience. But they have one thing in common: they practise science of the highest world standard, they have impressive achievements to their credit and different kinds of FNP support in their extensive CVs. We are launching the publication of our cycle; successive interviews will appear regularly on the FNP website.
Algorithms capture molecules
An interview with Dr Bartosz Wilczyński, bioinformatics researcher, by Anna Mateja
ANNA MATEJA: What path was it that led you, a computer scientist, to molecular biology and seeking answers to questions like how cells make decisions when controlling the production of nearly 30,000 different proteins?
BARTOSZ WILCZYŃSKI: After high school I chose computer science because I knew that with that education I could easily find a job. And so it happened. By the middle of my first year at university, thanks to a flexible course schedule, I was already working. But because I was studying computer science in the College of Inter-Faculty Individual Studies in Mathematics and Natural Sciences at the University of Warsaw, I began to take an interest in topics from other fields.
But you found a job in a corporation?
Yes. Although I had various interests, including research interests, I didn’t plan to become a scientist. I changed my mind when, thanks to the adviser on my master’s thesis, Prof. Jerzy Tiuryn, I visited the United States for a year to join the team of Dr Krzysztof Fidelis at the Lawrence Livermore National Laboratory in California. That visit worked out so well that after it I was encouraged to pursue a doctorate.
Why did it work out so well?
Because two papers arose out of the results of the work conducted during the fellowship. This was the turning point. At Livermore I encountered for the first time topics that closely combined issues of molecular biology with computational methods. This turned out to be particularly intriguing, because in California I could easily fill my day with various absorbing activities, but I realized that scientific work—writing programs modelling gene expression and gathering materials for publication—drew me in the strongest. Even though before my visit I didn’t consider myself an ideal candidate for a scientist.
After returning from the fellowship, I knew that I would begin my doctorate. Although I had written my master’s thesis on a topic from mathematics, highly theoretical, my doctoral dissertation would be about bioinformatics—building mathematical models explaining biological issues.
Photo: Dr Bartosz Wilczyński, photo by OneHD
What was it that intrigued you about bioinformatics? The possibility of combining research tools from such different disciplines?
For me, and probably for lots of scientists working in interdisciplinary fields, what was the most interesting appeared at the interface between various research disciplines. Besides, I did not especially enjoy writing theoretical works in mathematics or informatics, where problems are solved within fairly narrow specializations. By the natural order of things, the target audience for works of this type is narrow, sometimes just a few dozen people in the world. Practically speaking, it’s work for a lone wolf. And as I don’t feel that I was meant to sit in contemplation in the privacy of my study, I chose a field that requires me to work in a team—bioinformatics.
The topics I work on can also be approached more theoretically. Or biological problems can be treated exclusively as inspiration for the work of a computer scientist. I’m not suited to either of those approaches, because one of the main drivers of my activity is the possibility of cooperation with others, particularly if I can learn something from them during my work. It is in cooperation with biologists that we select a problem to be solved—ideally one that is interesting for both sides. Then, together with other mathematicians or computer scientists, we work on a computational model, which rarely lasts less than one year and often lasts two to three years. We present it to the biologists when it seems to us that the predictions obtained through our calculations will enable formulation of new biological hypotheses. Even if only a portion of them are verified experimentally, it means that our algorithms “capture” the molecular reality. Those moments reinforce the confidence that the choice of scientific work I made several years back, although unplanned, was not such a bad choice.
But it did not have to be that way, because a doctorate, even in bioinformatics, doesn’t foreclose any options.
That’s true—with a doctorate I could easily return to a corporation and work on something different. The reason that did not happen was due in part to the first reviews of my research projects, which were flattering and encouraging—for example from the Foundation for Polish Science (which enabled me to win a START stipend for young researchers) or from the Ministry of Science and Higher Education. At the beginning of the path, such an evaluation is very much needed, because confidence that you have made the right choice is not obvious even for PhD students who are doing very well. It was also significant that the grants not only enabled my scientific research, but also ensured the financial stability of the family I began while still a student.
During my postdoctoral fellowship at the European Molecular Biology Laboratory in Heidelberg, one of the most interesting places to work in this field, I was involved in the issue of gene regulation in embryonic development. The main interest of Dr Eileen Furlong, the head of my team, was the development of the mesoderm—the middle layer of the cells of the embryo, where, among other things, muscle tissue and the epithelium of body cavities are formed—in complex eukaryotic organisms (we worked on fruit flies). We were interested in the early stage of differentiation of the cells of the mesoderm, when it is necessary to observe at least several hundred genes simultaneously. Each changes expression in a non-accidental manner. We tried to determine which genes regulate each other and in what order.
What function does a computer scientist perform in such research?
Let’s start from the fact that the complexity of the process does not allow biologists to analyze it if they do not have a precise description of it in the computer. Because the mechanisms of genetic control of the activity of cells, described in the 1960s by Jacques Monod and François Jacob, are highly susceptible to mathematical description, I could juxtapose them with the knowledge obtained through state-of-the-art research methods, such as measurement of the level of expression of genes. But the mathematical models that had been used tended to be quite abstract and did not cover very many genes at the same time. My trip to Heidelberg coincided with the moment when scientists could analyze for the first time the regulation of gene transcription, taking into account what was happening at that time in the chromatin (the stringy substance occurring in the nucleus of a cell, the main component of chromosomes, which contain the genetic material of the cell). The research begun there led me to my current work, where we construct more global models covering not only individual genes, but dozens or hundreds of genes. Equally important, we are no longer referring to genes as abstract switches. We are trying to determine how chromosomes are arranged in the cell, and how the genes are arranged in the chromosomes, because this is relevant for the right ones to be activated. A description of these processes using computer models can provide biologists with an answer to the question of which genes are responsible for which processes occurring in the cell.
You describe it as if nature were governed by algorithms.
As far back as the 19th century embryonic development fascinated scientists because of its near-perfect reproducibility. Total determinism is an illusion, but it is worthwhile to inquire to what extent processes connected with regulation of genes are conditioned and to what extent they are governed by chance (which in its own way makes them even more interesting). We have a process that is strictly controlled and provides predictable results (all embryos of fruit flies are very similar to one another), but at the same time based on mechanisms with a high degree of randomness (such as the transport of molecules regulating transcription in the nucleus of the cell). To reflect both of these aspects on the scale of hundreds or thousands of genes, we have to apply various mathematical approaches.
This is an area of interesting research primarily thanks to the rapid progress in the field of subtle biochemical techniques allowing us to “peek” inside cells. It is possible for example to study the expression of genes at the level of individual cells, or to examine the structure of the chromatin in the nucleus of the cell. Consequently, complex measurements conducted for example on a thousand individual cells generate so much data that it requires advanced mathematical methods to harness and understand the data. Thus we try to build models that cover the random portion and the deterministic portion of the processes in question at more than one stage of regulation. This is still a challenge and interesting material for research.
In Heidelberg I became immersed for the first time so deeply in the details of molecular biology, and this happened mainly because I met people you could spend hours with talking about contemporary biology. Because in science the people we chance to come into contact with have a big impact. If we have the misfortune of encountering people who generate a toxic atmosphere, it can discourage even scientists who have a great research topic. In Heidelberg, the belief that I was working with interesting people on scientifically important issues was confirmed every step of the way.
What made them so special?
I can describe it using the example of my boss, Dr Eileen Furlong, who is by education a biologist without much of a mathematical background. I was the opposite: a mathematician fresh from finishing my doctorate who still had lots to learn about molecular biology. But we were both open-minded enough to work together on the project, from the moment the research issue arose, through discussions on the choice of the optimal mathematical method, to working up the results and writing the publication. I was responsible for only specific elements, but we openly discussed the whole project and designed experiments to perform. The work was interdisciplinary from beginning to end, thanks to which I saw that effective cooperation between the two fields does not consist of presenting readymade computational models to the biologist for verification. Or thinking up ad hoc analyses to quickly deal with results of completed experiments.
Now, after five years of independent scientific work, I know how hard it is on the organizational side. How much effort it takes to coordinate the endeavours of scientists from different fields, with their own research methods, different goals, and even different journals where they would prefer to publish their results. The backbreaking settlement of accounts for funding of interdisciplinary projects. You have to constantly overcome centrifugal force if the cooperation is not going to end only with some interesting conversations, but will actually lead to joint results and publications. In Heidelberg, as a postdoc I was happily relieved of mundane financial and organizational issues and exclusively devoted to science. But I became convinced that interdisciplinary research is possible and generates concrete results, and for that it is worth overcoming the difficulties I mention.
Photo: Dr Bartosz Wilczyński, photo by OneHD
If Heidelberg was so great, why after your fellowship of nearly three years did you nonetheless return to Warsaw?
I could have stayed there longer, but I was just a couple of years away from my 35th birthday. That’s a major boundary line for scientists, when you fall out of the category of “young researcher” and begin to be subject to different funding criteria when applying for grants. It was the right moment to return and test my strength as a scientist who leads his own projects, independently raises funds, and looks for his first collaborators among students. But it can’t be ruled out that if I hadn’t received a HOMING PLUS grant, designed for scientists returning to Poland from abroad, I would have extended my stay in Heidelberg by several years. I have to admit that thanks to the changes that have occurred in science in Poland over the last decade or so, young researchers in particular are in a much more comfortable situation than their colleagues who began their careers for example in the 1990s. But this doesn’t change the fact that returning to Poland from more scientifically advanced countries is not an easy decision, particularly if you have the opportunity to remain there longer.
For me, when I decided to return, apart from the grant I won (but also the desire to raise our children in Poland!) it was also relevant that I would be working scientifically at a place where you can have a big impact. In Poland there is still a lot of change underway in the structure for pursuing science. If I am a researcher in Poland, I have the opportunity to have my input on that, to influence the direction where decisions are being taken—implementing what I learned about that abroad. Science is fortunately governed by democratic principles, so all voices are heard, even those of younger and less experienced colleagues.
Some people say “fewer changes, more consequences.”
From the scientists I met in Heidelberg coming from Austria or Spain—countries that may not be in the very front ranks in terms of scientific success, but where they practise science at a very decent level—I heard that in their home countries nothing was changing. Nothing had changed for years. The system was functioning OK, so no one saw a need for example to launch additional grant competitions. I met lots of people from such countries who had chosen the US or the UK because there a young researcher has more chances to become independent. Based on that comparison, Poland is a much more dynamic location than some well-established countries.
Do you like to teach?
Yes—teaching is for me a highly rewarding experience. While scientific research, particularly interdisciplinary research, sometimes goes on for years before it delivers any interesting results (specialization is indisputably more efficient), teaching can provide almost instant satisfaction. The awareness that I enabled just one person to understand an issue that the person had no concept of half an hour earlier is a fantastic feeling. I value the possibility of leading classes because it brings knowledge into order, trains your communications skills and ability to convey knowledge in an approachable way. If I have presented something poorly, I will know right away because the students will be buried in their smartphones instead of discussing the topic. Of course this requires students who are eager to learn, and fortunately there are plenty such students at the University of Warsaw.
And did you like studying, for example biology?
In secondary school I hated it. Primarily because I was taught practically 19th-century biology, almost purely descriptive and not molecular. There were hardly any quantitative issues, when the correct conclusions are drawn from measurements and statistics. The discord between school biology and the exact sciences is so big that despite the many comments on the advantages of the interdisciplinary practice of science, students fall deeply into this pigeonholing. Practitioners of statistics and mathematics generally aren’t interested in contemporary biology, although they could easily find a place there to show off their talents. Meanwhile, many natural scientists suffer from the belief that if someone needs too many statistical or computational methods, the experiment should be designed differently.
The effect of this pigeonholing is depressing, as I learned when giving lectures on my research in Warsaw high schools. In the biology and chemistry classes everyone knew what a genome is, but providing quantitative data, for example on the average number of mutations differentiating between two people, caused panic. Or indeed any question that asks “How many?” Even though they could find the answer to the question about the number of mutations in a few minutes, using their own smartphone, where they could find the relevant information in Wikipedia and then make a few simple arithmetic calculations.
This is what gave rise to the concept of creating an online platform with programming tasks for secondary school students combining biology, chemistry and physics?
The problem of the divisions we are discussing is complicated and I have no ready solutions. It just occurred to me to try at the school level to interest young people in tasks that require knowledge from biology or chemistry as well as programming skills. Thanks to a grant from the Foundation for Polish Science and the commitment of some of the students from the bioinformatics science club functioning at my faculty, the project could be implemented. Since April 2016 nearly a hundred people have tackled these tasks (and some of them did great), so we have had some impact, though it’s hardly Pokémon Go! But I have no illusions that launching this type of portal, writing a book on the limitations flowing from excessive attachment to divisions between sciences, or conducting training sessions, will solve the problem. It is too complex, if for no other reason than because it affects too many people, not all of whom are willing to question their own way of thinking.
This is rather the beginning of work on the foundations that will take many years.
Or even several generations. But meetings with young people have reinforced my belief that it is worth devoting energy to this. Even if most of them still prefer to become specialists in only one field, they will at least learn that science overlapping different disciplines is also possible.
Dr Bartosz Wilczyński (born 1979 in Częstochowa) is a scientist at the Faculty of Mathematics, Informatics and Mechanics at the University of Warsaw. He is a winner of FNP programmes START (2007 and 2008), HOMING PLUS (2010), INTER (2012) and eNgage (2014).