As a child she wanted to be a medical doctor, today she researches the properties of the immune system. At the ICRC, she is part of Dr Jan Frič’s research team on Cellular and Molecular Immunoregulation. In December 2022, she was awarded the MU Vice-Rector’s Award for Excellence in Doctoral Studies, and she also supervises undergraduate students, manages projects and organises activities within the Young Immunologists Group of the Czech Immunological Society. Now Petra Lázničková is now facing a new “project”, to combine her scientific career with motherhood. As she says herself, it is about the set-up of our environment and conditions in which we function. On the occasion of the International Day of Women and Girls in Science, commemorated every year on 11 February, we asked Petra to share her experience.

Petra Laznickova

Photo: Petra Lázničková

Biochemistry as a space for connecting the dots

What was your path to science?

When I was a child, I wanted to be a medical doctor, but eventually I was tempted by biochemistry. I discovered that I didn’t like to learn things by heart. I prefer to try to understand the principles and context. I came to Brno from the Podkrkonoší region, as my brother was already studying here, and I also liked the atmosphere of the city. I completed my Bachelor’s and Master’s degree in biochemistry at Masaryk University, and then I had to decide what to do next. I was considering whether I had all the qualities needed for pursuing a PhD.

How did you evaluate your chances then?

The key is to think analytically. There are a number of scientific journals out there. When you are looking for a particular thing, you need to be able to pick out what is relevant to you from that mass of information and whether your hypothesis can be methodically tested. So I decided to do an Erasmus+ Traineeship for recent graduates first, to try out all aspects of day-to-day scientific work. I joined Professor Kamil Krance’s group at the Centre for Regenerative Medicine in Edinburgh, Scotland. His focus on haematology fitted well with my experience of studying neutrophils, one of the types of white blood cells that provide natural immunity. I spent a total of 8 months on placement in Scotland and found that I enjoyed the process – designing an experiment, conducting it, then evaluating it and finding context in the literature. Even before returning from Scotland, I met with Dr. Frič with whom I agreed on the realization of my doctorate within his team.

What specifically are you working on?

We look at the immune system, its function and signalling in terms of pathologies, i.e. specific disorders. As part of my PhD, I studied the immune system profile of children and adolescents who have successfully undergone treatment for neuroblastoma, which is a typical early childhood tumour arising from nervous tissue cells. The cooperation with Tomáš Kepák, MD, who has been working on the issue of late consequences of cancer treatment in childhood for a long time, was crucial for us.

What did you find out?

There are a number of articles on the study of immune cells in leukaemia survivors. This disease is more common than, say, neuroblastoma, and therefore the patient groups for research are broader. Paediatric leukaemia patients have been shown to carry some immune damage throughout their lives. They show premature onset of disorders that are otherwise common in elderly patients, such as heart and breathing problems or frequent infections. We have found scope for our research in patients with neuroblastomas, which are solid tumours, where similar features of immunity have not been so well explored. Surprisingly, we found that although the immunity in these patients shows signs of aging early after treatment, within about 4 years after therapy, later the cellular properties return to normal values. This gives hope for the same prospects for cured patients. However, the question is whether other problems would show up later, e.g. in the generation of thirty-somethings. We would therefore like to extend our research to other age groups.

A busy day for a researcher

What does your typical day look like?

During my PhD, I planned my own experiments, worked on the components one by one and consulted the procedure with my supervisor. I am now a post-doc, so I typically start my day by dealing with emails. I then work on my own experiments or work with a fellow technician on the flow of the sub-experiments she is conducting for the project. Since I also supervise ICRC Academy students, one undergraduate thesis, and am advisor to a beginning PhD student, I have dedicated time for their experiments and questions as well. Together as a team, we then process the results of our experiments and prepare papers for publication in scientific journals. Unfortunately, we do not have the capacity to be able to process samples from thousands of patients. However, we are trying to go more in-depth and test the functions of cells so that our research has a specific purpose and meaningful value.

In addition to your research activities, you are also active within the Czech Immunological Society, what does it entail?

I helped founding the Young Immunologists Group in June 2021. We created everything ourselves from scratch, i.e. the name, logo and related administration. We organize lectures, workshops and online seminars for (not only) young researchers in the field. But we also deal with more informal topics such as work-life balance or experiences from internships abroad. I myself have been surprised by the response to our activities. At the same time, it has been a great experience for me. I couldn’t have imagined how much time it would take to organise a lecture, to find researchers who would have a big reach and attract the audience, to make and send out invitations or to find sponsors. It’s a really diverse activity.

Photo: In December 2022, MU Vice-Rector Šárka Pospíšilová awarded the Award for Excellence in Doctoral Studies at MU to 33 graduates and their supervisors, including Dr. Jan Frič and Petra Lázničková

You mentioned work-life balance – how do you manage your free time? How do you spend your time outside the lab?

I try not to live only by science, also because if there was some obstacle and one had no compensation by another activity, it would destroy one’s whole world. My husband also helps me, reminding me that it’s time to rest. I like to hike in the mountains, in the countryside and play sports. I cycle, ski and cross-country ski, depending on the season.

How has Covid-19 influenced you?   

The immune system has been the subject of a variety of science communication activities thanks to the covid era. It has, I think, improved awareness of what immunity is. But I was worried at first, probably like everyone. It was something unknown. And there was a lot of speculation. My relatives and friends kept asking me for my expert opinions and recommendations, which was not easy. I didn’t want to get into analysing unfounded assumptions.

In terms of research, I managed to get involved in a number of projects. Most recently, as part of the National Recovery Plan (Exceles programme), we will be comparing the immune system in post-covid patients who have returned to normal life and those who have developed post-covid syndrome. So from that point of view, I see coronavirus as an opportunity to contribute to research. Moreover, in the early days of the pandemic, a number of publications flowed from the regions with the first outbreaks and appeared in prestigious scientific journals because they needed to gain the necessary reach. However, it now appears that not all the published findings met the requirements for research quality, and it will be up to us scientists once again to rectify this situation and find out what is relevant.

Women in science do not benefit from the set-up of the education system

How do you feel as a woman in science? 

In this respect, a lot depends on who you meet. I feel rather supported in my community. Moreover, I feel that there are currently many young female scientists. The other thing is that, as they progress in their careers, their numbers are declining because they want to have a family and they have to adjust the time they spend on their work.

You’re facing a similar milestone in your career because you’re expecting a baby soon. What would make it easier for you to continue your scientific work? 

I am fortunate that Dr. Frič understands this shift in life and considers it natural. We’ve agreed on an arrangement so that work doesn’t come at the expense of my family time. After an initial “offline” period where I will be fully committed to the baby, I have the option of working part-time or from home. Incidentally, my colleague has spent the last almost 5 years this way and it certainly hasn’t taken her out of research. At the same time, I feel a commitment to the students I supervise, so I will be dedicated to them as well, so that they can present their results as part of their studies.

According to the data from the National Contact Centre – Gender and Science 2022, the proportion of women in science in the country is 27 % and the representation decreases with each level of study and level of scientific function. What are the gender-related pitfalls of a career in science? 

Czech scientific society is set up in such a way that after a PhD one should gain experience abroad as a post-doc. This can be beneficial in terms of experience, but it clashes with the time when, for example, my female peers are already starting families. If I can compare it to the UK, they have much more freedom there to complete the individual education levels more quickly. For example, instead of the 3+2 model, the undergraduate degree can be combined into four years of Bachelor’s studies. Then you can go straight on to a PhD, which can take as little as 3 years to complete. This opens up the possibility to still gain further international experience in time. In our country, one of the options is to do a PhD abroad and then return. This will account for the time spent abroad and you can then, for example, apply for certain grants for which this experience is a prerequisite.

How competitive is the scientific world?

A lot. To stay in science, at some point you need to become independent and move from post-doctoral researcher to junior team leader. To make that shift, you need to find your own scientific field of expertise and your own source of funding.

That seems like a very unstable environment, how do you feel about it?

You’re right, it’s a very unstable environment. It is only at a later stage that scientists can get permanent positions at some institutions. This already guarantees a certain stability, where the institution keeps the scientist, even if sometimes only part-time. The way I see it, without grants, we wouldn’t exist. So I myself have been actively involved in grant writing since I was a PhD student to help our research.

Diversity and positive role models move people forward in their careers.

What is the gender ratio in your team?

We defy the statistics a bit because we only have three men and seven women. At the same time, I see a representation of different experiences, mindsets, skills and hobbies, which moves us forward. I have mentored four female students – three in the ICRC Academy and another one now in her undergraduate degree. I remember when resumes came in from the ICRC Academy, most of the candidates were women. So you can see that women have that energy in them, but unfortunately it does not last for everyone, in the long run.

Photo: Cellular and Molecular Immunoregulation Research Team

Do the results of your research affect your lifestyle in any way?

In immunology, there is a lot of talk about the effect of lifestyle on the ageing body or the immune system, whether it is dietary habits, smoking, alcohol consumption or physical activity. I’ve been active since I was a kid, so it’s more about affirming that the direction my parents led me in is the right one.

Do you follow fashion trends? Do you keep up with them?

I don’t follow fashion trends much, but I often solve practical problems. I’m quite tall, so it’s hard for me to find a dress of the right length, for example. This has led me to slow-fashion, where I see that the material is of good quality, sewn by, for example, a mother on maternity leave, or by established domestic brands. I don’t need to buy a lot of stuff, but rather invest in fewer quality pieces.

What are your future plans?

I would like to stay in science for as long as possible. A lot of my colleagues are leaving for companies after post-doc. I’ve never really been drawn to the commercial world. I’m slowly evolving on my journey. At first, I wasn’t sure whether to go for a PhD, which I successfully completed. Then I wasn’t sure if I could manage leading people as a post-doc, and now I see, it’s okay. Maybe it’s also about building confidence. Personally and professionally, I’ve had positive feedback from my students and colleagues about working together, which makes me happy.

Do you feel supported in your further development?  

During my PhD, my supervisor had regular meetings with me to discuss current research-related issues. He always ended these meetings with such an optimistic tone that it was almost contagious. Even if a particular thing didn’t turn out the way we imagined, I was still motivated and the idea that I didn’t have to crumble from every problem remained. So that’s what I take away from our collaboration. Furthermore, for example, I participated in a leadership course for several days within the ICRC, so I have those opportunities here as well.

What message would you give to young girls and women considering a career as a scientist? 

If a woman feels that science could be fulfilling for her, there is always a way. She just needs to find the right mentors to support her. They can be male or female, it’s their qualities that matter. I admire people who do their work well, regardless of gender.

Thank you for the interview.

 

Gender equality and diversity are some of our core values at the ICRC. We have been a granted the “HR Excellence in Research” award since 2021 and have been implementing the Gender Equality Plan since 2022. As a result, we are gradually succeeding in setting up equal opportunities among male/female employees so that they have the opportunity to make the most of their talents, skills and expertise in science and research. 

We focus on several key thematic areas – Institutional arrangements for gender equality policy, Personnel policy, Salary policy, Reconciliation of personal and professional life, Organisation culture and workplace relations. For example, we routinely offer part-time work and subscribe to the principles of transparency and fairness in gender pay. We are one of the first employers to have undergone an equal pay analysis using the LOGIB tool, and we are also the very first representative from among hospitals in the country.

We employ women in both scientific and administrative positions. It is not a secret that our head is also a woman, Prof. Irena Rektorová. Out of a total of 406 employees, 55% are women. Specifically, we have 40% female researchers in relation to male researchers. Other female colleagues work in scientific support positions such as clinical study coordinators, data analysts and laboratory technicians.

More information can be found at: https://www.fnusa-icrc.org/en/career/equal-opportunities/

The second US patent has been awarded to a team of scientists from the International Clinical Research Center (ICRC) in Brno, the 3rd Faculty of Medicine of Charles University (3. LF UK), the Institute of Scientific Instruments of the Czech Academy of Sciences (ISI CAS) and Cardion s.r.o. They developed a new technology for the device, commonly known by the acronym ECG. The high-frequency electrocardiogram (UHF-ECG) brings more accurate diagnosis to doctors and patients. By reducing the number of inappropriate treatments, it promises cost savings throughout the healthcare system.

In order for the heart to pump blood into the body, there are regular coordinated contractions of the atria and ventricles. These contractions are triggered by electrical impulses. The ECG is one of the basic tests in cardiology. It records the electrical activity of the heart in the form of an electrocardiogram (a time recording of ECG waveforms), which allows for subsequent evaluation. A conventional ECG measures up to approximately 150 Hz. “We have started to observe higher frequencies in conventional ECG measurements, especially in the 150-1000 Hz region, and their behaviour between the different electrodes on the chest. We found that these frequencies can occur at different times in each electrode within the so-called QRS complex, which records the impulse for ventricular contraction. Depending on whether the patient has any defect in the electrical impulse in the heart chambers,” explained Pavel Leinveber, head of the ICRC Biomedical Engineering Centre.

In a healthy heart, both ventricles work simultaneously, i.e. synchronously. In a patient, for example after a massive heart attack, there may be so-called ventricular dyssynchrony, where one ventricle or part of it is activated with a delay. The heart does not pump blood efficiently, reducing its output, which causes considerable health problems for patients. Electrical conduction disturbances in the heart are treated using various pacing techniques. The choice of the appropriate technique and the correct execution of the technique are important factors for the effective function of the heart. Conversely, improperly chosen and implemented pacing can induce ventricular dyssynchrony. UHF-ECG technology offers easily accessible information on the electrical activation of the ventricles, which can be used both for the selection of the appropriate pacing technique and for immediate control of correct pacing directly at pacemaker implantation or during follow-up checks for correct pacemaker function.

EKG1

Fig. 1: Application of UHF-ECG in practice

The new method promises ease of use for physicians, as it uses conventional ECG electrodes and their standard clinical layout on the patient’s chest. The electrical action of the heart chambers is then clearly visible on so-called depolarisation maps. These are based on the high-frequency signal and illustrate in colour how the electrical excitation moves through the ventricles of the heart muscle. The technical solution is also cheap and easily accessible.

“For patients, the test is non-invasive, with results available within minutes. It provides physicians with completely unique information that could help optimize surgical procedures and pacemaker settings in clinical practice. Patients with an optimally placed and adjusted pacemaker remain physically active longer, which positively affects their health and well-being,” adds Doc. MUDr. Karol Čurila from the Cardiac Centre of the 3rd Medical Faculty of Charles University and the University Hospital Královské Vinohrady in Prague. In addition to the improvement in the health of patients, we can expect their longer working activity and other socio-economic benefits for society.

EKG2

Fig. 2: Example of depolarization map

Czech scientists have already received a second US patent for their discovery. “Thanks to this, no one can manufacture or sell the device for the duration of the patent, without our consent and a share of the profits”, explains Pavel Jurák from the ISI CAS. This patent extends and protects the methodology required to use UHF-ECG technology in practice. Other patents are also applied for within the European Union. The device is currently being used experimentally by 11 hospitals in the Czech Republic and Europe to confirm its effectiveness. These facilities include St. Anne’s University Hospital Brno and the University Hospital Královské Vinohrady in Prague. The next step is now being taken by the start-up company VDI Technologies, s.r.o., founded in 2022. Its goal is to move the device to clinical use, ensure its certification and subsequent market launch. This will allow the technology to be expanded into everyday medical practice.

More information:
www.medisig.com/vdi/
http://www.isibrno.cz/
www.lf3.cuni.cz

Media Contact:
Ing. Jiří Erlebach, Head of PR and Marketing Department, Spokesperson of FNUSA, tel.: +420 543 182 006, jiri.erlebach@fnusa.cz
Ing. Pavla Schieblová, PR Department, Institute of Public Relations of the CAS, tel.: 734 218 279, schieblova@isibrno.cz
Ing. Marta Reichlová, PR Manager, 3rd Faculty of Medicine, Tel.: +420 267 102 217, marta.reichlova@lf3.cuni.cz

The International Clinical Research Center (ICRC) in Brno is part of the new ADDIT-CE project, focused on the early diagnosis of Alzheimer’s disease (AD). AD affects millions of people worldwide every year and significantly affects the quality of life of both the patients themselves and their loved ones. It also represents a societal burden associated with the reduced employment of the sick, the costs of their treatment and related social services. Although we cannot yet cure AD, early diagnosis can slow down the progression of the disease. The ADDIT-CE project is funded by the Excellence Hubs programme, which supports the collaboration of all key partners driving innovation in AD diagnostics. Leading research teams from Brno and Bratislava thus have the opportunity to establish links with representatives of industry and with decision-making bodies of the state administration responsible for setting effective policies to combat dementia. The expected output is not only the cultivation of ecosystems for the early detection of AD, but also the effective use of new technologies in practice.

ADDIT_CEPhoto: The initial meeting of the ADDIT-CE project managers (author: CEITEC)

As part of the ADDIT-CE project, researchers from the Central European Institute of Technology of Masaryk University (CEITEC MU), Masaryk University, ICRC and the Biomedical Center and Institute of Neuroimmunology of the Slovak Academy of Sciences collaborate with private biotechnology companies, specifically BioVendor, Multiplex DX and Geneton. Patients and their loved ones will be represented by organizations such as the Slovak Alzheimer Society, the Czech Alzheimer Society, the Memory Center and the Czech Brain Aging Study. The regional government will be involved through the Ministry of Health of the Slovak Republic and the South Moravian Innovation Center. The project coordinator is Jozef Hrizt from CEITEC MU.

The ICRC is part of most of the project packages that deal with the search for early biomarkers of the disease, i.e. measurable values indicating the presence of the given disease or the assumption of its occurrence. As stated by MUDr. Kateřina Sheardová, Ph.D. from the ICRC Dementia research team: “We will examine these new biomarkers in the sera and cerebrospinal fluid of people at risk of developing Alzheimer’s disease who are participants in our Czech Brain Aging Study. We will compare them with the neuropsychological and magnetic resonance data that we monitor as part of our program.”

The Czech Brain Aging Study (CBAs) is a national longitudinal study, carried out at the ICRC and FN Motol, which investigates early functional, metabolic, structural and genetic biomarkers of AD and other dementias in the blood, cerebrospinal fluid and magnetic resonance imaging of patients, on a long-term basis. We thus have at our disposal a unique database mapping changes in the structure and metabolism of the brain over time in healthy individuals, in patients with mild cognitive impairment and in dementia.

“We will also investigate the protective effect of lifestyle by analyzing the data we are currently collecting as part of the study on positive psychology and spiritual well-being. We can then put the subsequent findings into practice in the form of recommendations on how to influence lifestyle as part of prevention,” adds Sheardová.

Together with the Slovak MEMORY Center, we are also preparing an intervention study for patients with a higher risk of AN. As part of the study, we will offer physical activity, sleep control and yoga techniques that positively affect mental health.

The initial meeting of the project managers took place on January 25, 2023 in the premises of CEITEC MU in Brno. Details of the meeting and more information about the ADDIT-CE project can be found in the CEITEC press release.

Disclaimer: Funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or European Research Executive Agency. Neither the European Union nor the granting authority can be held responsible for them.

In an interview with Irena Rektorova, a physician and head of the International Clinical Research Center (ICRC), a joint workplace of St. Anne’s University Hospital Brno (FNUSA) and the Faculty of Medicine, Masaryk University (LF MU), we talked not only about how to run a research institution – unique in the Czech Republic – that combines research with direct patient care. We also asked about the EXCELES project and how to attract talented foreign scientists.

prof. Rektorova

Since January 2022, when Irena Rektorova became the head of the ICRC at FNUSA, many things have happened. A joint workplace agreement with the Faculty of Medicine and a cooperation agreement with the Faculty of Science of MU have been concluded. Within the framework of the National Recovery Plan, one of the three pillars of the project focused on neurodegenerative brain diseases with cognitive impairment has been led, and thanks to the ICRC, FNUSA has been able to take over the coordination of the entire project. She also managed to negotiate the recruitment of a foreign scientist coming with an ERC Proof of Concept grant and much more.
In all this, Irena Rektorová continues to work in the outpatient clinic, coordinates the Neuroscience Programme at the Central European Institute of Technology (CEITEC) and leads her research team. She also sits on the boards of international medical organisations. Now she gave an interview for Vědavýzkum.cz.

Keeping in touch with live science

Do you remember that turning point when you got into organising and leading research activities?
The first time was probably when I became the head of the Centre for Cognitive Disorders at the First Neurological Clinic at the Faculty of Medicine of Masaryk University and FNUSA. I was leading a team of clinicians, organizing professional seminars, teaching of students and PhD candidates and thanks to that I was “staying in science”.
With the establishment of CEITEC, a large shared laboratory MAFIL (multimodal and functional imaging) was created, fully operational since 2015, where a number of neuroscientists from both university hospitals, the Faculty of Medicine and other Brno institutions found refuge. While at the hospital we could only do research on brain imaging with MRI half a day a week, and only if it was not needed for an acute patient examination, at CEITEC two excellent three-tesla MRIs (3T MRI – ed.) were available purely for research. In addition, we were able to recruit great engineers, psychologists and scientists with backgrounds other than that of a neurologist, psychiatrist or radiologist.
That was a huge leap. From my medical practice, I was used to getting phone calls from patients all the time, and suddenly I could leave the hospital for two days a week and just focus on research, my students and my team. Working with PhD students and medical students interested in clinical research was and still is very recharging, although I have much less time for my team now than I used to.
I built this from basically scratch and in the process learned how to manage things – from constantly writing grants and checking that research is recruiting patients or volunteers as planned, to overseeing data quality, processing and interpretation, communicating results at conferences, to writing manuscripts and overseeing publication outputs to ensure that the project is evaluated to be excellent.

Clinics and research under one roof

What then brought you to the head of the FNUSA-ICRC?
The great advantage of the ICRC is that basic and clinical research is carried out under one roof. We are in a hospital where we have access to patients, plus researchers from the teams are very much connected and work on joint projects, which makes it easier to translate basic research into clinical practice. And the reverse is also true – we can test different side effects, such as the toxicity of new drugs on organoids in basic research. The interconnectedness goes both ways.

In this respect, you are a rather unique institution in our country. Was that also the main reason for its creation?
That would be a naive idea. (laughs) There was a lot of lobbying behind it, so that Brno would have two important institutions, the ICRC and CEITEC. And because at first it looked like only one would be created, they were not completely positive towards each other, which persisted for a long time.
In fact, one of the reasons why I was tempted to become the head of the ICRC was to normalize relations, which I hope I have succeeded. I don’t so much mean the relationships of individual researchers who understood the need to work together, but rather those of the “heads”.
I also managed to link the ICRC to Masaryk University. Since July, we have been a joint workplace of FNUSA and LF MU. Thanks to the connection with the university, we can also better access some structural grants from the Ministry of Education, Youth and Sports. With the creation of this “Brno platform” we are much stronger and more competitive, also in terms of fundraising.

So, what is the focus of the strengthened ICRC at the moment?
The big topic is that, through the ICRC, FNUSA is now coordinating one of the EXCELES call projects within the National Recovery Plan. It involves 11 institutions with a budget of just under 600 million crowns for 3.5 years. The project is expected to result in the creation of a National Institute for Neurological Research as an advisory body to the government.
At the same time, research on neurodegenerative diseases of the brain is being conducted, divided into three pillars: one on cognitive issues, which includes Alzheimer’s disease, one on motor disorders such as Parkinson’s disease, and then neurodevelopmental diseases such as dystonia or epilepsy.

Beyond the clinic

Could you elaborate on how the ICRC works in terms of research infrastructure?
In addition to the 23 research teams, we run 6 core facilities, such as the Center for Clinical Studies, the Biomedical Engineering Facility or our clean rooms for the development of cell and tissue therapies. These offer services not only to our researchers, but also externally – to the entire country and nearby foreign institutions.

On your website you also announce services in technology transfer and cooperation with the private sector. How are you doing in this area?
To put it simply – a hospital as a contributory organization cannot create spin-offs. The ICRC is unique in that it is the only research institution in the Czech Republic that functions within a hospital. We are working to negotiate with the Ministry of Health to find a way to transfer technology. And although we do not currently have sufficient apparatus or legislative conditions for this, a commercial department could certainly make a living in ICRC – several patents have already been created on our grounds.
The establishment of a joint workplace with Masaryk University gives us the opportunity to deal with some patents together, so we are now discussing mutually beneficial possibilities of cooperation. Contract research in the area of clinical studies in patients and animal models has been very successful at the ICRC for a long time and is one of the sources of funding for our research teams and core facilities.

“That’s just the way it is” – the pitfalls of international collaboration

Broadening the scope, what are the ICRC’s main international partners? And does this bring any pitfalls in addition to the obvious advantages?
From the very beginning, the ICRC has maintained a strategic partnership with the Mayo Clinic in the USA. It was facilitated by the financial “budget” dedicated to this collaboration at the time, which we no longer have today. So, immediately after I joined, I approached Professor Worrell, who was the coordinator of this collaboration at the Mayo Clinic, to clarify what research groups they would be interested in for joint grant submissions – without asking for a financial injection from us.
Unfortunately, this is the way it is at prestigious institutions – for example, it is also the case at Karolinska Institutet – that you have to pay for collaboration. Which is quite hard to imagine, but unfortunately it was probably important for the connection with the Mayo Clinic. It was subject to wide criticism, and I myself was critical of it, but it did help in some ways. For example, the fact that some of the scientists were able to go to America and bring back the know-how they had acquired, that helped to kick-start some of our groups. (laughs)
Today, however, we do our research with international partners purely through international or European grants, mostly Horizon-type grants, which we have managed to get.

How the ICRC convinces excellent scientists

How does it happen that a person gets the opportunity to create his or her own research team? At least at the ICRC?
Nowadays, through an open international selection process, which is determined by the new rules for the creation and dissolution of research groups that I pushed for when I joined the ICRC and which we have managed to put in place. Such an institution needs to be flexible and responsive over time. Some groups are simply not successful – they don’t have great enough publications, they don’t get grant funding, and they are not rated well by the “ISAB” (International Scientific Advisory Board) that we use to evaluate research teams. And therefore they will disappear.
Other groups will come into existence as people come in who are excellent in research and have the desire to start their own team with us. And because there is a limited number of excellent scientists in the Czech Republic, we are interested mainly in foreign junior scientists who have already achieved something in research and have the drive – such predatory pikelets.

How do you get to them? Do you actively seek them out?
If we know of a great scientist who would be a good fit for our portfolio, we can now put out an open call for applications. Anyone from home or abroad can apply, and we advertise both home and internationally. In the end, we choose the best one.
I would also like to push for researchers to come to us with their grants, especially of the ERC type. In December, Adam Williamson, a Canadian, will join us with an ERC Proof of Concept grant, and he is setting up a junior group here and partly at CEITEC VUT and is already applying for other grants. He will focus on non-invasive brain stimulation techniques, particularly electrical stimulation of deep brain structures, in patients with degenerative disease or epilepsy.

And in this particular case, have you approached this scientist directly? What attracted him to you?
First of all, he has a long-standing collaboration with Eric Glowacki, who came to CEITEC VUT with a similar ERC grant, and their activities are in the field of research that I have long been involved in clinically with my team at CEITEC MU, i.e. non-invasive stimulation methods. On the one hand, he has seen that foreign scientists with expertise in this field are beginning to meet with us. And finally, he saw that the ICRC is much more flexible and will create better conditions for him than Aix-Marseille Université and Karolinska Institutet, where he also works or has worked, and where, among other things, there are much higher “overheads”, so he will get more from his grant for his research here.

Did he really know this himself, or did you convince him that he would find such conditions at the ICRC?
It was partly negotiation, partly Eric Glowacki convinced him, partly me. He’s been here several times, he’s seen the premises, I introduced him to the director of the hospital, the dean of the Faculty of Medicine knows about him. I think he got excited because I introduced him to the researchers in my group – he immediately tested how capable they were.
In addition, we are offering him the opportunity from the very beginning to lead the Ph. D. students, which we are able to share with him. His projects are already filed with the ethics committee, which usually approves them within a month or two. In short, as soon as he joins us, he can start doing research, which is something he can’t get elsewhere.
But there are certainly bureaucratic, operational and other obstacles that you encounter when acclimatising foreigners…
To be honest, I have to say that the Czech authorities prevent foreigners from entering the country in the first place – for example, by requiring them to pay for insurance in advance. In addition, some foreign workers imagine that they will have everything provided for here, from a nursery for their children, a job for their partner to housing. And although we try to accommodate them within the boundaries we set, we can’t do everything for them. Fortunately, we have an HR department that has been working on internationalisation as part of the HR Excellence in Research project.

Irena Rektor’s normal week

Finally, I would like to focus on how do you yourself actually function in all this, or what does your, undoubtedly, busy working week look like?
When I started in January, I thought I would be able to “shake things up”, but I am still shaking things up (laughs) – there are too many activities. What I know for sure is that I have meetings all day Monday, Tuesday I spend at CEITEC, Wednesday I am “ambulating” at the hospital, and Thursday and Friday I deal with things mostly related to the ICRC. In between that, of course, we submit grants and publish, then there’s the weekend when I do work for the European Academy of Neurology and a whole bunch of other things.

What do you struggle with the most…?
Emails. I’m starting to hate them. (Laughs) The trouble is that all my meetings generate more work and it’s impossible to just meet. But I have to say that I have great administrative teams around me, such as the operations, HR and Finance Departments, which process all the big grants, and a Grant Office that other hospitals don’t have – which is also how we can do the EXCELES project, which otherwise only universities can do.

Author: Vědavýzkum.cz (MP)
Photo: Patrik Uhlíř
Article adapted for the ICRC website with permission of the author.

Irena Rektorová completed her internship at McMaster University in Canada before finishing her medical studies at the 1st Faculty of Medicine of Charles University, despite her parents’ fears that she would not finish her interrupted studies (which was not common then as it is now). After specializing in neurology, she joined St. Anne’s University Hospital (FNUSA) as an assistant professor at the 1st Neurological Clinic. She developed her academic career at the Faculty of Medicine of Masaryk University, where she was appointed Professor of Neurology in 2012. She headed the Centre for Cognitive Disorders and now serves as the head of the Centre for Abnormal Movements and Parkinsonism. In 2011, she built a research group at the Central European Institute of Technology (CEITEC) MU focused on applied neuroscience. Her research and medical practice focus on neurodegenerative brain diseases, cognitive disorders and dementia, or brain imaging and non-invasive stimulation techniques. In January 2022, she became the head of the International Clinical Research Center ICRC, a joint workplace of FNUSA and Faculty of Medicine MU. Internationally, she has been involved, for example, in the committee of the patient organisation European Parkinson’s Disease Association (EPDA), served as scientific secretary of the International Association for Parkinson’s Disease and Parkinsonism (IAPRD) and, since July this year, became a member of the committee of the European Academy of Neurology (EAN), the largest European expert neurological organisation cooperating with 47 national neurological societies.

The project entitled “Unveiling the molecular determinants of aging to design new therapeutics (MAGNET)” has now successfully concluded at the International Clinical Research Center (ICRC) in Brno. Its main focus was research of selected ageing-associated diseases, understanding their mechanisms and finding potential targets for their treatment. The project, which gained great support from the European funds, attracted to Brno a number of both junior and established researchers, headed by Dr. Manlio Vinciguerra.

The main research objectives of the project consisted in unveiling the role of epigenetics, mechanosensors, immune response, intracellular transport, and mitochondrial dysfunction in the pathogenesis of aging-associated diseases. The specific problems targeted by the research activities were liver diseases such as hepatocellular carcinoma, innate immunity defects, cardiovascular and neurodegenerative pathologies.

The project was awarded over 177,5 mil. CZK in 2016 by the Ministry for Education, Youth and Sports of the Czech Republic (MŠMT). Funded through the Operational programme Research, Development and Education (in Czech OP VVV), it aimed at attracting a renowned international scientist, Dr. Manlio Vinciguerra, to establish his research group at the ICRC. At the time Dr. Vinciguerra was a Senior Scientist working at the University College London (UCL), London United Kingdom.

“The funding from the MŠMT through the OP VVV program helped us to significantly advance the understanding of aging-associated pathologies, which represent a true burden to the society” says Manlio Vinciguerra, the coordinator of the project. “It gave me the chance to join a very vibrant scientific environment at the ICRC and to establish my research group. I am extremely thankful for this opportunity” he continues.

The team employed other Principal Investigators of the ICRC, i.e. Irena Koutná, Giancarlo Forte, Gorazd Bernard Stokin, Jan Frič and Jaeyoung Shin; and attracted promising young researchers and students of more than 10 nationalities. Thanks to the available funds, we were also able to send our Ph.D. students for internships abroad.

“The international nature of the research team created thanks to the OP VVV funding was really a game changer. It created a lively and varied environment which helped the cross-contamination of scientific ideas. The result of this process has been excellent science.” comments Giancarlo Forte, who is also the Head of the Center for Translational Medicine at the ICRC, where the research was performed.

Focused on excellent and clinically meaningful research, the project led to disclose the role of histone protein macroH2A1 as a determinant of liver disease progression and of hepatocellular carcinoma aggressiveness, making it a potential target for future treatments. Moreover, the project allowed for the identification of novel predictive markers for heart failure, the proteins Yes Associate Protein (YAP) and heterogeneous nuclear ribonucleoprotein C (hnRNPC), together with providing the first multiscale map of the human failing heart. Additionally, thanks to the financial support of MAGNET project, scientists at the ICRC described how chronic inflammatory signalling affect the extracellular matrix and also the phenotype of immune cells.

“A number of young and established researchers participated in this very successful project. It was an honour for our institution to host it. The scientific objectives reached are truly remarkable” stress Prof. Irena Rektorová, the Head of ICRC.

These results were published in prestigious peer-reviewed international journals, like Hepatology, Science Translational Medicine, Nature Communications, Circulation Research, EMBO Molecular Medicine, Theranostics, iScience, GeroScience, Lancet Health Longevity, Acta Neuropathologica Communications and others. In terms of numbers, there were more than 100 publications affiliated to the project, with 50 % of them in Q1 journals. First quartile representing the best journals according to series of metrics.

“The project entailed the use of tissues and cells harvested from patients hospitalised at the premises of St. Anne’s University Hospital Brno (FNUSA), so that the results have a concrete translational potential” says Ing. Vlastimil Vajdak, director of FNUSA hospital.

MAGNET project also helped to establish the Cell and Tissue Engineering Facility (CTEF) at the ICRC, a unit endowed with ISO 9001 certification (quality management system) and GMP manufacture permit which manufactures advanced therapy medicinal products (ATMPs) including cell therapy and tissue engineered products.

The funding also allowed establishing or consolidating prestigious international collaborations with UCL (UK), the European Institute for Systems Biology and Medicine (EISBM, France), the University of Barcelona (Spain), the University of Geneva (Switzerland), the University of Southern California (USA), the University of Porto (Portugal), the University of Perugia (Italy).

Supported by the European Regional Development Fund – Project MAGNET
(No. CZ.02.1.01/0.0/0.0/15_003/0000492).

 

Heart failure is the leading cause of death worldwide. Scientists at the International Clinical Research Centre (ICRC) in Brno have identified a potential target for the treatment of heart disease that is related to the location and function of a protein called hnRNPC. They have now published their findings in the prestigious journal Science Translational Medicine, opening up the possibility of finding new treatments.

Cardiac diseases are accompanied by intense modifications of the architecture of the heart muscle tissue, a process which is defined as negative remodeling. During this process, a scar is formed within the muscle which impairs its contractile function and eventually leads to the failure of the organ in the long run.

Despite the advances in therapies and prevention, heart failure remains the leading cause of mortality worldwide. This pandemic accounts for over 1.8 million deaths every year, which means more than one in three deaths in the world are caused by heart failure.

For many years, scientists have known that the progression of heart failure is associated with the modification of the internal functioning of the cardiac cells, including those processes controlling the maturation of RNA molecules. These processes are important for the production of the structural proteins, which account for the ability of cardiac cells to produce force, contract and make the heart beat. Altered RNA metabolism in the diseased heart is considered largely responsible for the disease.

The research group led by Dr. Giancarlo Forte at the International Clinical Research Center (ICRC) of St. Anne’s University Hospital Brno and Faculty of Medicine, Masaryk University, finally identified how the formation of the scar in the heart leads to altered RNA metabolism by affecting the localization and function of a protein named hnRNPC. These results might pave the way to the design of new treatments based on the interference with the displacement of the protein.

The research, which is the subject of a publication on the leading international journal Science Translational Medicine, started in 2015 and was conducted mostly on human patient samples thanks to the decisive collaboration of the Center of Cardiovascular and Transplant Surgery (Centrum kardiovaskulární a transplantační chirurgie, CKTCH) Brno. Other collaborators of the study include researchers from Central European Institute of Technology (CEITEC) in Brno, as well as from the University of Melbourne (Australia), King’s College, Imperial College London and the University of Surrey (UK).

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Microscopic images of tissue from a healthy (left) and diseased (right) human heart. The muscle tissue is shown in red and the appearance of the scar in the diseased heart is shown in blue.

The research was generously supported by the European Regional Development Fund – Projects ENOCH (No. CZ.02.1.01/0.0/0.0/16_019/0000868) and MAGNET (No. CZ.02.1.01/0.0/0.0/15_003/0000492), European Union Horizon 2020 Research and Innovation Program NANOSUPREMI (No. 690901) and the Czech Science Foundation.

Reference:
Martino F, Mysore Varadajan N, Perestrelo AR, Hejret V, Durikova H, Vukic D, Horvath V, Cavalieri F, Caruso F, Albihlal WS, Gerber AP, O’Connell MA, Vanacova S, Pagliari S, Forte G.
The mechanical regulation of RNA binding protein hnRNPC in the failing heart. Sci Transl Med (2022) https://www.science.org/doi/10.1126/scitranslmed.abo5715.

A scientist’s dream! An event that happens once every 384 years! And the immense joy of all involved, the humility and respect for the work done. All of this is embodied in the success of the scientists from the Loschmidt Laboratories of the Faculty of Science of Masaryk University and the International Clinical Research Center (ICRC) in Brno. Manuscripts of four of them were all accepted in one day for publication in prestigious journals Nature Catalysis, ACS Catalysis, Analytical Chemistry and Computational and Structural Biotechnology Journal.

Mountaineers climb peaks, athletes break records, artists create masterpieces. For scientists, publishing articles in peer-reviewed journals is a core part of their work. In doing so, they spread awareness of their research, get feedback, develop collaborations with like-minded colleagues, and move the research forward. The most prestigious journals are those that are peer-reviewed and have a high impact factor, i.e. a value reflecting the average citation rate of all articles published in a journal over a certain period. Impact journals are ranked within their fields according to various metrics and are divided into four quartiles. The best ones are in the first quartile.

This elite group includes all the journals in which Martin Marek, Zbynek Prokop, Jan Velecký and Jan Mičan from Loschmidt Laboratories have managed to publish. Jan Velecký, for whom the acceptance of his first-authored article was a condition for the completion of his doctoral studies, wittily compared it to the milestones of a person’s first smile, first word, first day at school or first A or F grade at school. His colleague Michal Vašina, who has also recently enjoyed publication in the internationally recognised journal Chem Catalysis, likened the process of publishing a paper to the aging of wine. It happens that scientists have to rewrite and refine an article for several years before their “gran reserva” is accepted for publication.

Specifically, the accepted manuscripts describe the catalytic mechanism of the enzyme luciferase, the improvement of plastic-degrading enzymes by protein engineering, a microfluidic platform for monitoring enzymatic reactions, and the development of a new database for predicting the effect of mutations on protein solubility.

In his congratulatory message on social media, Prof. Petr Slavíček from the University of Chemistry and Technology in Prague calculated that with the current scientific performance of the team, the probability of 4 papers being accepted in prestigious journals at the same time is 0.09%, and we can therefore expect a similar phenomenon again in 384 years. We congratulate all the authors and wish them to break the statistics and celebrate more similar achievements soon.

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Celebrating the success of the research teams, 11/11/2022 – from left Michal Vašina, Jan Velecký, Jan Mičan, Zbyněk Prokop, Martin Marek

Nature cannot do without enzymes – proteins that speed up chemical reactions in all living organisms. For example, we owe our beer and wine to enzymes; we wouldn’t enjoy hard cheeses and, in principle, wouldn’t do laundry without them. But people also use enzymes in biomedicine, industry, and environmental protection. Unfortunately, relatively few enzymes perform optimally, so scientists have been working for decades on searching for more efficient enzymes. In doing so, they keep running into a fundamental question: Is it better to modify existing enzymes through protein engineering or to search for new ones in nature’s vast diversity?

Researchers from the Loschmidt Laboratories at RECETOX, Faculty of Science, Masaryk University and the International Clinical Research Center (ICRC), in collaboration with colleagues from ETH Zurich and the University of Greifswald, decided to go down the route of searching for new enzymes. They published the results of their six-year research project in the international prestigious journal Chem Catalysis. Their aim was to find more efficient variants of an enzyme family that can degrade halogenated hydrocarbons polluting the environment. The search began in genomic databases, which currently contain hundreds of millions of gene sequences that encode previously unknown proteins. Using the in-house web tool EnzymeMiner, they were able to select the most promising candidates from this plethora of sequences. “You could compare it to finding needles in a haystack. With EnzymeMiner we can distinguish the needle from the straw very well. However, in the next step we need to find out if the selected needles are sharp enough – this means to experimentally verify that the selected enzymes are fast enough,” said Michal Vašina, the first author of the study.

Therefore, the researchers then prepared these selected candidates in the laboratory and studied their properties using two microfluidic platforms – modern technologies that can handle miniature sample volumes and save time. The first platform, MicroPEX, was used by the researchers to systematically characterize enzymatic reaction rates, while the second platform, KinMAP, gave them insight into the actual mechanism of enzymatic reactions. “The savings in time and money are tremendous. Thanks to this method, we can measure the same amount of data in a single week that would take months to obtain with conventional technologies,” said the microfluidic expert Zbyněk Prokop.

Coming back to the question from the beginning of the article, whether it is better to discover or engineer new enzymes, this scientific study gives a clear answer. Historically, the first enzymes degrading halogenated hydrocarbons were identified more than 30 years ago, while protein engineering has been used for their modification for 25 years. During this time, the properties of twenty-five discovered and more than one hundred modified enzyme variants have been described. When comparing the data obtained, the researchers found that the newly obtained enzymes had better properties than any previously discovered or modified enzyme from the same family.

So how to get more efficient enzymes? Based on their experience, the scientists in the Loschmidt Laboratories answer: “Let’s not underestimate nature. Thanks to its diversity, it has an arsenal of effective enzymes just waiting to be discovered!”

Publication:

https://doi.org/10.1016/j.checat.2022.09.011

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The synergy of advanced bioinformatics and microfluidics helps to find efficient enzymes for recy-cling chemical synthesis intermediates, degrading environmental pollutants, or preparing active pharmaceutical ingredients.

Representatives of the ICRC received a certificate from the Swedish Ambassador H.E. Frederik Jörgensen on the successful completion of the gender pay equity analysis by Logib.

The International Clinical Research Centre (ICRC) in Brno is among 18 institutions and companies awarded for the Gender Equity Assessment. The presentation of the certificates took place on 12 September 2022 at the Embassy of Sweden in the Czech Republic, aptly underlining the importance of the Nordic countries in equality and diversity issues.

The ICRC is among the first employers to undergo this assessment. At the same time, we are the very first hospital representative in the country. We thus subscribe to the principles of transparency and fairness in gender pay. The analysis is part of the implementation of the FNUSA-ICRC Gender Equality Plan for the period 2022-2024.

The Logib tool is an analytical tool that allows employers to assess the status of equal pay for their employees. It is a summary of the gender pay gap by gender and educational attainment, length of experience with a given employer, and the demands and responsibilities of the job.

The first step is to assess the situation, analysing the trend from 2021 and 2022. Based on the results, we will develop a plan for the next steps towards a fairer remuneration system. We want to weigh everyone equally, as the scale our representatives received as a gift with their certificate suggests.

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ICRC representatives, Zuzana Hochelová and Milan Košdy, at the certificate ceremony

Preventing diabetes or understanding the causes of Alzheimer’s disease – these are also topics supported by the Molecular, Cellular and Clinical Approach to Healthy Ageing (ENOCH) project, whose investigators met in Brno at the end of September. More than a hundred representatives from five top Moravian research centres evaluated the achievements of ENOCH so far. The project has succeeded in creating a unique space for mutual cooperation of experts in the field and the application of the qualities of each of the participating workplaces. The knowledge gained is a further step on the road to active and healthy ageing.

The Continental Hotel in Brno hosted the ENOCH (MolEcular, cellular and cliNical apprOaCH to healthy aging) project meeting on 29-30 September 2022. Led by the International Clinical Research Centre (ICRC) in Brno, the platform includes partners from Palacký University in Olomouc, Masaryk Cancer Institute, University of Ostrava and Olomouc University Hospital. The project was born in 2018 with the idea of coordinating research centres dedicated to topics related to population ageing.

As Professor Irena Rektorová, Head of the ICRC, reminded us in her introduction, “The goal is not immortal life, but a healthy old age, i.e. to age actively and healthily.” The development of new preventive, diagnostic and therapeutic solutions for age-related disorders should contribute to this. “ENOCH purposefully unifies current research on healthy ageing and makes full use of its potential to share know-how, experts and resources across the region. It is the networking of different institutions that is crucial to ENOCH’s contribution, as each of the researchers has unique practices and expertise to offer the field”, adds project coordinator, Dr. Gorazd B. Stokin of the ICRC.

Specifically, the research teams are studying, for example, dementia, cancer, chronic inflammation and heart disease. These disorders affect a large part of the population in advanced age and therefore affect not only the elderly but also their families. The consequences are also reflected in the healthcare system and the budget for health and social services.

The results are coming out both in the field of basic research, i.e. in laboratories, and in medical practice. For example, the Kardiovize team at the ICRC, with the support of the ENOCH project, has designed a diabetes prevention programme. Based on measurements of the health status of the local population, the researchers have put together a set of effective measures in the form of a preventive lifestyle programme, which takes place regularly at the St. Anne’s University Hospital in Brno and offers participants training in a lifestyle that suits them while supporting their long-term health.

After two years of metal restrictions, the annual meeting of the ENOCH project was once again held in full attendance. It offered a discussion on the progress of the project implementation, both in terms of the fulfilment of the binding indicators and benchmarks, and in particular on the research activities carried out by the different teams. The Steering Committee also met and positively evaluated the performance and results of the project so far and also focused on the commitments and plans for its subsequent sustainability. The programme also offered presentations by three guests. Dr. Robert Zorec from the University of Ljubljana addressed the topic “Noradrenergic hypotheses of cognitive decline and astroglia”. Dr. GIampiero Leanza from the University of Catania followed with an online presentation on “Noradrenaline and the regulation of spatial memory”. The trio was rounded off by Dr Kenneth Moya from the Department of Biology, École Normale Supérieure, Paris with “Neuroprotective action of the homeoprotein Engrailed 1 and motoneuron physiology”.

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The ENOCH project (Molecular, Cellular and Clinical Approach to Healthy Ageing, CZ.02.1.01/0.0/0.0/16_019/0000868) is funded by the European Regional Development Fund. The implementation phase of the project ends in June 2023, when a five-year sustainability period will follow.

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