Let’s beat cancer by understanding cellular architecture! That is the motto of the new, fully internationally staffed research group of the NICR. It was created in the Prague node of the NICR at the Institute of Biochemistry and Experimental Oncology of the First Faculty of Medicine of the Charles University. The team was put together by Martin Sztacho. The Laboratory of Cancer Cell Architecture investigates, among other things, the molecular basis of oncological diseases.
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What should we imagine under the term ‘cancer cell architecture’? Does it have the same meaning as in construction, that is, is it about the organisation of mass in space?
Cancer cell architecture refers to the complex organisation and mutual interaction among all the internal components of a cell, which jointly determine its behaviour and functions. We can thus imagine it like a machine tuned to perfection, where each part has its precise place and role.
Although the analogy with architecture is relatively fitting, it is important to bear in mind that cellular architecture is much more dynamic and complex than the architecture of buildings. Unlike buildings, which are static, cells constantly adjust their internal structure in reaction to changes in the surrounding environment. This is especially true of tumour cells, which can often survive even extreme conditions, such as oxygen deprivation, and develop mechanisms of treatment resistance. The architecture of tumour cells exhibits numerous deviations which enable their uncontrollable growth and spread. From a biological point of view, these deviations are fascinating but for cancer patients, they are often life-threatening.
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Is the research of cellular architecture important for understanding the emergence of tumours?
It is utterly crucial! The structure and organisation of cellular components directly influence all processes that take place in the cell. It is known that changes in cellular architecture play a key role not only in the emergence of cancer but also in various other disorders, including for instance neurodegenerative diseases. A disruption of cellular architecture can lead to aberrant changes in many cellular processes. One possible consequence is uncontrollable cellular division, which is a characteristic feature of cancer. By expanding our understanding of architectonic changes in tumour cells, we open the door not only to earlier diagnosis but also to related research aimed at developing new and more efficient treatment strategies. One could thus say that research of cellular architecture is a key step to a better understanding of the origin and development of cancers. In the future, it will certainly improve the prognosis of cancer patients.
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Would it be possible to build a concept of cancer treatment and prevention on a better understanding of cellular architecture?
One option is to influence molecular changes using specific substances. There are some promising initial results showing that some already known cancer drugs, for instance cisplatin or the Czech mitoxantron, can incorporate into protein condensates, dynamic intracellular structures which often change during the emergence of a tumour.
The long-term goal is to develop substances that would specifically target only certain concrete pathological changes in cellular architecture without damaging the structure of healthy cells. That would lead to more effective cancer treatments with minimal side-effects, but it is also important to bear in mind that the road to this goal will be long and thorny.
Cancer cells are highly varied, and their behaviour also significantly differs case by case. That is why there is no universal solution for all tumour types. It will be necessary to investigate, in detail, the changes in cell architecture that take place in different types of tumours, and then develop specific treatment strategies for each type. This research is demanding in terms of time, finances, and personnel, and it must be based on an interdisciplinary collaboration of researchers and clinicians. But I am convinced that thanks to joint effort, we will in the future reveal the secrets of cellular architecture and use this knowledge to fight cancer.
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Was it difficult to build a new research group with international scientists and to choose the people on which the project will rely?
It was, and still is, a demanding task. Especially the recruitment of colleagues from non-European countries requires considerable administrative effort. Fortunately, we have received significant support from the NICR but also EURAXESS and rectorate of the Charles University. With their help, we are trying to simplify the process of employing foreign experts – and this may in turn help create more favourable conditions for future international employees at least at our faculty.
In terms of choosing particular individuals, what was decisive was above all their scientific experience, skills, enthusiasm, but also personal compatibility with other team members. In this respect, my international experience really helped me. I have organised a number of online interviews and gradually selected candidates who best met the requirements. Neither nationality nor gender played a role in this process. Thanks to significant support from the NICR, and now also partial support to excellent scientists provided by the Charles University, we are managing to improve conditions for the international staff. Still, Czech science financing is rather challenging, which limits the attractiveness in comparison to other countries.
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What do you share in your international group?
Naturally, we all share a passion for science, but we have also discovered other common interests, such as good food. It is an excellent way of getting to know each other in a less formal way. We are just at the beginning but already we had the opportunity to compare meals prepared by our female colleagues from Poland, Spain, and Turkey. Unfortunately, I am so far the only man in the team and my cooking skills are limited but I believe I, too, will be able to contribute by preparing some traditional Czech dish. Still ahead of us is a virtual culinary trip to Peru and Iran, which we are all very much looking forward to.
I tried to select people who are not only outstanding experts but also mutually complement each other in terms of their personality. I believe we are creating a great team that will achieve excellent results.
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By the way, what qualities should a good group leader have?
Thanks to my own experience with working abroad, I realised the importance of flexibility. Each person has different needs and different expectations, which is why it is important to find an individual approach to each team member. Naturally, everyone has different ideas about what a good boss should be like, but I found I worked best under bosses who had a lot of empathy but at the right moment could also put pressure on me. That is why I think the ideal leader should be both strict and kind, able to motivate and inspire, just, but above all consistent and thorough. I am trying to make sure that our group will be a place where everyone can develop and feel like their work has meaning.
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How and in collaboration with whom do you study cellular architecture? To what extent is this collaboration facilitated or made more effective thanks to the existence of NICR?
Our team is now complete and even the lab is almost completely equipped with high-quality instruments and getting to the right ‘operational temperature’. It will take a while yet, but I am so happy we have managed to create a group and equip a lab over such as short period of time. Now comes the time to start fully engaging in science, which is why everyone had come here and moved to the Czech Republic.
Aside from our various international collaborations, we greatly appreciate that we have managed to establish very good relations with neighbouring labs in the Institute of Biochemistry and Experimental Oncology, which are likewise part of the NICR. We hope that during the international CACR 2024 international conference we will get to better know some other research groups and then establish further collaborations. I already have in mind some colleagues with whom I would like to discuss some opportunities for further cooperation.
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What international projects are you involved in and what does it involve?
There are several such projects. International cooperation is very important for us, because it helps us gain access to the most recent findings and technologies, to compare our results with the results of other research teams, and to build an international scientific reputation for our group.
One important project is our cooperation with the Institute of Virology in Cologne, where together with Professor Akgül we investigate the molecular mechanisms linked to infection with human papilloma viruses and the development of cancers. Then there is the cooperation with colleagues from Yucatan. This year, we will together organise a workshop aimed at sharing our knowledge with younger researchers and thus strengthen international cooperation in modern histology. During this visit, I will also have the opportunity to present our research results at an international conference in Mexico.
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Which of your scientific results or experiences do you value the most?
I think perhaps the successful completion of a doctorate in a prestigious programme of the Max Planck Institute in Germany. Then I am also extremely grateful for getting the opportunity to work in Max Perutz Labs in Vienna, where I acquired very valuable experiences. Doctoral studies and work abroad have enabled me to establish valuable contacts and create a wide network of collaborators. After returning to the Czech Republic, I had the opportunity to work in the Institute of Molecular Genetics of the Czech Academy of Sciences as a deputy lab leader: there, I acquired some experience with solving various problems linked to running a lab.
Still, establishing one’s own lab is much more challenging than anything I had encountered before, when I was ‘just’ part of an established and functioning labs. That is why I feel proud that we have managed to create the Laboratory of Cancer Cell Architecture. I think it pushed me further in my ability to address complex issues…and this is still just the beginning.
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Given that you are in charge of a laboratory of cellular architecture, are you actually interested in architecture as such?
Yes, I am interested in architecture and construction as a reflection of their time and society. I feel especially drawn to brutalism, paradoxically because of its austerity and a sense of coldness. This style evokes in me strange emotions by the rawness and roughness of the masses of concrete. Perhaps I am attracted by how it differs from the complexity of living nature. When travelling through the Balkans, I realised how differently brutalism is perceived in different countries. While in Czechia it is often condemned, in the Balkans it often feels monumental and mysterious. That is determined also by the urbanistic context in which those buildings stand. My relationship to brutalism is naturally potentiated by my liking of sci-fi, where brutalist architecture often forms the backdrop of post-apocalyptic scenes.
