PhD Katarzyna Świderek obtained her master’s and doctoral degrees in physical chemistry from the Lodz University of Technology in Poland. She conducted research in laboratories across Poland, Germany, Spain, and the United Kingdom. Her work focuses on theoretical aspects of reactivity in cellular processes.
How did your journey with science begin?
My journey with science began relatively late. I was never one of those people who from the start knew what they wanted to do in the future and to be honest I always envied my peers who had clearly defined career goals. After graduating from XXXII High School in Łódź where I had fantastic teachers whose enthusiasm and dedication showed me that mathematics and physics could be truly fascinating I decided to try myself at the Faculty of Chemistry at Łódź University of Technology, especially since the faculty was planning to open a specialization in forensic chemistry which caught my attention. Unfortunately, it soon became clear that this would not happen. By then, I was doing quite well with my studie, so I decided to continue my education without a clear plan for the future. The turning point came in my fourth year when I chose a specialization in physical and computational chemistry inspired by the lectures of the legendary professor Ewa Hawlicka. This was a perfect choice. It turned out that computational chemistry has a lot in common with conducting an investigation. In computational chemistry, we use theoretical tools to try to understand how physical and chemical phenomena occur at the molecular level which are invisible for researchers in the laboratory but are known to occur because we observe changes over time. Computer models are excellent tools for creating possible scenarios and executing them and as many examples show, they are indispensable in studying various phenomena. It quickly became clear that computational chemistry combined with the study of biological processes, biochemistry and elements of pharmaceutical science became my passion.
What factors led you to decide to go abroad? What were the biggest challenges related to this decision?
In my case going abroad was a natural consequence of completing my doctoral studies and was mainly driven by the desire to continue developing and acquiring new skills during a postdoctoral fellowship which in my opinion, is crucial for anyone who wants to continue research work. A good catalyst for this decision was also the lack of any opportunity to continue working at my home university.
The biggest challenges I faced at the beginning of moving and continuing my work abroad were primarily logistical. For my first postdoctoral fellowship in Spain I moved with my 2-year-old daughter and for the second one in England I moved with two daughters. In both cases it required organizing not only my schedule but also the family’s weekly routine – arranging schools and simply adapting to live in a new place. In Spain an additional challenge was the language barrier. When I moved to Spain I didn’t realize how few people in the country spoke English despite it being a popular tourist destination. I myself did not speak Spanish at all at the time. Fortunately at the universities there were more people who spoke English and were willing to help. Over time I learned Spanish. However, one of the biggest challenges, in my opinion, remains the complex Spanish bureaucracy.
One of the significant challenges that young scientists face is the difficulty in securing stable positions at Spanish universities. In my case, despite conducting research for 13 years at Spanish universities I am still employed as a Postdoc and the contracts that have allowed me to continue up to this point had to be won in open national competitions. Only receiving the Ramon y Cajal contract, due to its prestige, has given me the opportunity to apply for a permanent associate professor position. The issue with permanent positions at public universities affects many talented young Spanish researchers who often decide to move and seek employment at other universities abroad.
What benefits does your work in an international scientific environment bring compared to working in Poland?
Changing research groups whether in Poland or abroad always brings benefits in my opinion. It allows for broadening horizons, offers new perspectives on certain issues and enriches us with experiences not just scientific ones. It exposes us to new scientific challenges and expands our skill set. During stays in other laboratories, researchers improve their knowledge and technical aspects of their work. I experienced this during my doctoral studies when, besides working in my main research group led by Prof. Piotr Paneth, I had the opportunity to spend several months in the experimental crystallography laboratory of Prof. Grzegorz Bujacz at another department of my university as well as during a 3-month internship at the Helmholtz Centre for Environmental Research-UFZ in Leipzig. In both cases the experience of all the people who supervised my research played an important role in shaping my final doctorate.
During my stays at foreign universities, I learned a lot, not only about new computational techniques but also about work organization methods. Perhaps most valuable were the opportunities to participate in many fascinating scientific discussions. Being in other laboratories allowed me to observe the mechanisms by which these groups function which has significantly influenced how I manage my own work and the work of the students I currently supervise.
Do you maintain contact with Polish scientific communities?
Of course! Naturally I maintain contact with my PhD supervisor – Prof. Piotr Paneth. Until 2019 we worked together on a research project that culminated in the defense of a PhD by a student who completed part of her work at our university in Spain. In 2019 a PhD student from Prof. Maciej Szaleniec’s group at the Jerzy Haber Institute of Catalysis and Surface Chemistry of the Polish Academy of Sciences in Kraków spent three months with us. The results of his research, developed in our laboratory, were included in a scientific article published in 2021 in the renowned American journal ACS Catalysis. I also meet with many researchers from Poland privately or at international scientific conferences and some of them visit us during our annually organized mini-conference: Trends in Enzyme Catalysis (TrEnCa, https://www.biocomp.uji.es/trenca.html).
What are you currently working on and what is the main subject of your research?
The main research topic in our group is enzyme catalysis. For these studies we use the QM/MM computational method for the development of which Professors Arieh Warshel, Michael Levitt and Martin Karplus were awarded the Nobel Prize in 2013. Currently we are focusing on two main directions.
The first focus is on the drug design process, specifically inhibitors that could slow down processes catalyzed by selected pathogenic enzymes. In this case, using rational drug design methods we aim to understand the chemical process occurring at the molecular level in the active site of the studied protein enzyme. This understanding is then used to propose small organic molecules that are geometrically and electrostatically compatible with the shape of the active site. The full drug design procedure is a very complicated and multi-step process. Our approach represents the first stage which serves to propose potential candidates. The compounds suggested at this stage can then be synthesized in organic laboratories and subjected to further studies, such as toxicity tests, which cannot be predicted at the computational modeling level.
The second research theme involves a very general issue: trying to answer a question that has been a topic of discussion among scientists for decades—what physicochemical properties are responsible for the remarkable catalytic power of enzymes. In nature many chemical reactions that take place in seconds with an enzyme would take more than a million years without it. Identifying the source of enzymatic power, and above all, the ability to influence its behavior could allow scientists to design new enzymes – especially for catalyzing reactions that do not occur in nature.
What are the latest achievements in your field of research that particularly interest you?
The latest achievements in my research field that particularly interest me revolve around two experimental techniques. Firstly, there is the technique allowing the synthesis of proteins with desired characteristics through iterative rounds of genetic diversification known as Directed Evolution. Professor Frances Arnold was awarded the Nobel Prize in 2018 for her contributions to the development of this technique. The second technique of note involves non-trivial methods for introducing non-canonical amino acids into protein sequences. The incorporation of chemically alternative functional groups into protein sequences, which were previously based on only 22 naturally occurring amino acid residues, opens up entirely new possibilities in protein design. In the realm of theoretical research a breakthrough achievement, in my opinion, was the implementation and practical application of artificial intelligence (AlphaFold) for predicting previously unknown protein structures.
What is your most significant scientific achievement or discovery? Why is it important?
I hope that the most important discovery is still ahead of us. This thought is the driving force behind my work and motivates me to continue my research. One significant scientific achievement is our contribution to understanding the origin of enzyme catalytic power. When we began our research on this topic there were many theories among scientists attempting to explain how enzymes accelerate chemical reactions. These included the “compression effect” theory and the “spatiotemporal hypothesis” both suggesting that the active site, where substrates bind, maintains close contact between two functional groups participating in the chemical transformation. Another theory – the “dynamic effect” – suggested that very rapid movements of the protein structure occurring on the same time scale as the chemical reaction facilitate its course and consequently lower the energy barrier. Interestingly, none of these theories explained the behavior of the unrelated enzymes we studied. The only theory that proved correct was electrostatic reorganization, which refers to the specific electric field exerted by the protein macromolecule on the active site promoting the catalyzed reaction. In our research we found a linear correlation between the electrostatic potential generated by the protein in the active site and the energy barrier of the chemical reaction. Knowing that the electrostatic potential can be used as a quantity to monitor during the design of novel enzymes with new functions is very exciting and is what we are currently working on.
What scientific problems in your discipline are you most looking forward to solving and why?
I think that despite the enormous technological progress in recent years, computational chemistry still requires more efficient computers to simulate large macromolecules such as proteins. To apply precise levels of theory and accurately predict the behavior of these systems on an appropriate time scale, we need greater computational power. The scientific community is eagerly anticipating the application of quantum computers. Unfortunately, access to such machines is still limited and the application of algorithms is too complex.
What are the biggest challenges in your scientific work?
One of the biggest challenges is time, or rather the lack of it. Working at the university a significant portion of time is consumed by preparing and conducting teaching activities. Additionally I conduct initiation training for new group members, as unfortunately, the undergraduate studies in chemistry at my university do not sufficiently prepare students for the specific area of computational chemistry.
Apart from that, like any researcher, a standard challenge is securing funding for research. However, possibly even more important than funding is attracting talented and ambitious students.
What are the most important research questions you plan to address in the near future? What development directions do you see in your field?
Currently one of the main issues our group is addressing is the search for enzymes that can be redesigned to degrade plastics. This is a significant problem considering that, according to UN data 19–23 million tons of plastic waste enter aquatic ecosystems annually, polluting lakes, rivers and seas. Unfortunately, the degradation of these materials can take between 20 and 500 years, depending on their composition and structure, making it crucial to find effective methods for their breakdown. The choice of this research direction is a natural consequence of the current problem affecting our entire planet.
Are there practical consequences or potential applications of the results of your research? How do you see their impact on society or the economy?
One of our goals, as mentioned earlier, is to use theoretical tools to design enzymes with new desired functions. If we manage to develop theoretical procedures enabling this, it could revolutionize industrial production. Many production lines require very harsh conditions (high temperature or pressure) or toxic catalysts to carry out specific chemical processes. Enzymes have the great advantage of operating under mild conditions which could save a lot of energy in such processes. Moreover, enzymes are far more environmentally friendly and their use in transforming or degrading environmental pollutants could contribute to improving living conditions for people and bring us closer to regenerating natural ecosystems.
What advice would you give to young scientists at the beginning of their scientific careers?
First and foremost, every young scientist should ask themselves if science is their passion as a scientific career is a demanding endeavor that usually extends beyond a 40-hour work week. Being a researcher in any field is inherently linked to a series of successes but also, unfortunately – failures. It’s crucial to be prepared for the latter. We often get the impression that only successes count because scientists tend to highlight them. From my experience, failures, although frustrating and sometimes hard to accept, often contribute more to our research than all previous achievements.
The best advice I can give to younger colleagues is to leverage the knowledge and experience of senior colleagues. This can help solve research problems that they have already encountered. Be creative and courageous, and look for new paths that others have not yet explored. Take advantage of the opportunities provided by scientific conferences. These events allow you to keep up with the latest advancements in your field, spark original ideas for future research, and establish contacts that can lead to interesting collaborative projects in the future.
Fot. Unsplash
