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.
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.
Irena Rektorová: As a hospital, we cannot co-found a spin-off
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.
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.
ICRC concludes its MAGNET project on ageing
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 affec
t 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).
(No. CZ.02.1.01/0.0/0.0/15_003/0000492).
We have identified a new potential target for the treatment of heart failure
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).
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.
Fourfold joy in Loschmidt Laboratories
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.
Celebrating the success of the research teams, 11/11/2022 – from left Michal Vašina, Jan Velecký, Jan Mičan, Zbyněk Prokop, Martin Marek
Scientists developed a new method for discovering more efficient enzymes
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
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.
We want to be fair
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.
ICRC representatives, Zuzana Hochelová and Milan Košdy, at the certificate ceremony
ICRC-led healthy ageing research counts its successes
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”.
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.
Detailed pathogen detection in Alzheimer’s disease patients
Scientists from several research teams at the International Clinical Research Centre (ICRC), a joint facility of the Masaryk University Faculty of Medicine and St. Anne’s University Hospital in Brno, focused on microbial infections and Alzheimer’s disease. The link between the two has been demonstrated in many studies, and the research focused on the frequency of the most common viral and bacterial pathogens in the brains of Alzheimer’s patients.
The paper, entitled “Increased occurrence of Treponema spp. and double-species infections in patients with Alzheimer’s disease,” was published in the scientific journal Science of The Total Environment (IF – 10.75).
Alzheimer’s disease (AD) is an irreversible, progressive neurodegenerative pathology. It accounts for 60-80% of cases of dementia. Dementia is a general term encompassing memory loss and the gradual decline of other cognitive abilities, often severe enough to interfere with an individual’s daily life and independence. The origin of Alzheimer’s disease is not yet fully understood. The disease is characterised by a pathological cascade of protein clotting. One of these is amyloid, whose function is to protect the brain from infectious agents, i.e. viruses or bacteria. There are theories that the action of a particular virus or pathogen may cause this protein to clot more than is permissible and thus trigger the pathological cascade.
For the detection of five bacterial and five viral pathogens, a multiplex PCR assay kit has been developed in collaboration with BioVendor, where all of the aforementioned pathogens can be detected simultaneously. “Although the link between microbial infections and Alzheimer’s disease has been demonstrated in many studies, the contribution of pathogens to the onset of Alzheimer’s disease remains unclear,” said the first author of the paper, Dr Michal Nemergut from the Loschmidt Laboratories of the MU Faculty of Science and the ICRC. “Therefore, we investigated the frequency of the ten most frequently reported viral (HSV-1, EBV, HHV-6, HHV-7, CMV) and bacterial (Chlamydia pneumoniae, Helicobacter pylori, Borrelia burgdorferi, Porphyromonas gingivalis, Treponema spp.) pathogens in serum, cerebrospinal fluid and brain tissue of Alzheimer’s disease patients.”
Serum and liquor samples from 50 patients with Alzheimer’s disease and 53 control subjects without cognitive deficits were used. The samples and data were provided by the Czech Brain Aging study – a national aging study led by Kateřina Sheardová, MD, and Prof. Jakub Hort, MD. A significantly higher frequency of patients with Alzheimer’s disease who were positive for Treponema spp. was observed compared to controls (62.2% vs 30.3%). Furthermore, a significantly higher incidence of cases with two or more concurrent infections was confirmed in patients with Alzheimer’s disease compared to controls (24% vs 7.5%). The studied pathogens were detected with comparable frequency in serum and cerebrospinal fluid. In contrast, Borrelia burgdorferi, human herpesvirus 7 and human cytomegalovirus were not detected in any of the studied samples.
This study provides further evidence of an association between microbial infections and Alzheimer’s disease. “The results show that parallel analysis of multiple pathogens and detection of their occurrence from multiple different biological samples provides interesting additional information, and this methodology should be considered for future studies working with this hypothesis in the context of Alzheimer’s disease.” said Katerina Sheardová, MD.
New uses of cardiac MRI
Scientists from the Noninvasive cardiac imaging – CMR team at the International Clinical Research Centre of St. Anne’s University Hospital in Brno have published a study entitled “Stress pulmonary circulation parameters assessed by a cardiovascular magnetic resonance in patients after a heart transplant”. It was published in Scientific Reports (IF 4,996) and deals with the use of cardiovascular magnetic resonance in the assessment of selected parameters of pulmonary function.
“The aim of this study was to investigate novel pulmonary circulation stress parameters in patients after heart transplantation. These patients were hypothesized to have mild diastolic dysfunction, which is more pronounced under stress conditions. The results of comparison of the obtained parameters with the control group of patients confirm this assumption. We were also the first to use “ratio” parameters, which work with the ratio of stress and rest parameters” said the first author of the paper, Lukáš Opatřil, MD.
The pulmonary circulation parameters obtained by non-invasive methods are not completely new. Resting forms in different forms and obtained by different methods have been studied for years. However, the most recent method is cardiac magnetic resonance, which offers significant advantages over other methods and is the only one that can determine stress parameters. From the analysis of data obtained in this way, parameters such as pulmonary transit time (PTT), pulmonary transit beats (PTB) and pulmonary blood volume index (PBVI) can be obtained. Similarly, their variations during exercise can be obtained.
These parameters could be used in the future to determine diastolic dysfunction. Thus, a study conducted on a group of 48 heart transplant patients provided further evidence of pulmonary circulation parameters obtained by cardiac MRI. It investigated stress parameters in this group as a potential marker of diastolic dysfunction and introduced ratio parameters as potential new biomarkers.
Schoolchildren of the Visegrad Four learn according to the HOBIT programme
More than 1,700 primary school pupils from the Czech Republic, Slovakia, Poland and Hungary have received special training on stroke and heart attack through e-learning. A total of 152 classes from 29 primary schools and 56 teachers from the Visegrad Four countries participated in the project “V4 HOBIT: Saving Lives in the V4 through Health Education in Schools”.
The V4 HOBIT project was launched in March 2021 and its main coordinator is the Public Health Group of the Cerebrovascular Team of the International Clinical Research Centre of St. Anne’s University Hospital in Brno. The project partners are Semmelweis University (HU), Jagiellonian University in Krakow (PL) and University Hospital of L. Pasteur (SK).
The HOBIT programme has been running in Czech schools since 2014. However, it is new for teachers and pupils from the other three countries. In Slovakia, pupils from 68 classes in 10 schools learned how to recognise the symptoms of a stroke or heart attack and what to do in that moment. Most of them were from Košice, but there were also schools from Bratislava, Považská Bystrica and Trstená. In Poland, most of the schools from one city, Krakow, participated. In total, there were 24 classes from 5 schools. In Hungary, schoolchildren from different schools and towns participated in the project. The 28 classes from 9 schools came from cities such as Szeged, Nyírbátor, Zalaegerszeg or Szigetszentmiklós. The Czech Republic was represented by 32 classes from 5 schools coming from Ostrava, Brno, Ústí nad Orlicí, Domažlice and Štětí.
HOBIT educates through simulation scenes
The e-learning of the HOBIT educational programme consists of three parts. First, pupils go through a short section of several test questions to find out how much they already know about stroke and heart attack. Then they watch a video and finally go through the test again.
In each of the participating countries, pupils’ knowledge of the selected diseases increased by at least 10% after completing the full test. The biggest jump was in Slovakia, where the numbers jumped from an average of 44.8% (pupils’ success rate on the first questions) to 59.5% (pupils’ success rate on the final test). The smallest difference between the first and second tests was in Hungary. While Hungarian pupils passed the first test with an average pass rate of 53.5%, they achieved a pass rate of 57% in the second test.
One test is not the end of the project
Around 1,700 pupils from the V4 countries took the e-learning and tests in two rounds. The results allowed the research team to compare what the pupils remembered from the previous testing and thus evaluate the effectiveness of the international HOBIT learning platform.
“The result of the overall testing of the pupils’ success rate in the second round is very similar to that of the first round, ranging from 55% to 60%. For us and for the teachers, this means that the HOBIT education programme makes sense. These diseases (note: stroke and heart attack) are part of our everyday lives. Pupils are enthusiastic about the programme and learn something they can really use in their lives. They are not so helpless in crisis situations,” says Renata Hejnová, the coordinator of the HOBIT programme in the Czech Republic.
The e-learning of the HOBIT training programme is still active on the website https://projecthobit.eu/ in all four languages. If you are interested in taking part in the training programme, you can contact the coordinators and get the necessary information by e-mail: projekthobit@fnusa.cz.
The implementation of the training programme in schools was carried out by GrapePR in Slovakia, Agencja Pretty Good in Poland and Diamond Agency in Hungary. In the Czech Republic, schools that had already been involved in the HOBIT programme in previous years were contacted.