Martin Toul received the Doctorandus award in natural sciences from the Veolia on Sunday, November 26th. The award is given to young scientists for research in natural sciences as part of the Czech Head 2023 competition. He was awarded for his research on the functions of the staphylokinase protein, which is used in the treatment of stroke. Martin Toul clarified the functioning of this protein in his work, enabling an up to tenfold increase in its effectiveness in treatment.

Martin Toul, photo: Irina Matusevic, source: Masaryk University

The Czech Head, the most prestigious scientific award presented to scientists in our country for their patents and discoveries, has announced the winners for the year 2023. One of the awardees is Martin Toul, who, as part of the team of Protein Engineering and the Loschmidt Laboratories at Masaryk University, focused on the functioning of enzymes at the molecular level. He explored their greatest limitations and how this knowledge could be utilized to improve and practically apply them in industry or medicine.

Martin received the award at the ceremonial gala evening. If you missed the broadcast on Sunday, November 26, 2023, on ČT2, you can watch it later on the Czech Television iVysílání.

Enzymes, molecular machines with catalytic activity, play a crucial role in all living cells, facilitating essential chemical transformations for life, such as digestion, respiration, or muscle contraction. Nowadays, enzymes find broad applications in biotechnology, synthesizing pure drugs, being part of laundry detergents, or serving as biosensors and modern medicines. However, the efficiency of enzymes often falls far from the expected optimum for industrial and medical applications, reducing their effectiveness and broader use. In his research under the guidance of Prof. Zbyněk Prokop and Prof. Jiří Damborský, Martin Toul focused on the detailed characterization of enzymes and uncovering the molecular basis of their inefficiency and limitations. Thanks to this knowledge, enzymes could be improved through so-called protein engineering, addressing all the mentioned pressing issues.

The laureates of this year’s Czech Head were selected from dozens of nominations by an expert jury composed of leading Czech scientists, including the emeritus rector of VŠE, Richard Hindls, psychiatrist Cyril Höschl, neurosurgeon Vladimír Beneš, and others. The winners of this 22nd edition were introduced at a press conference on Friday, November 24. A comprehensive overview of all awardees can be found HERE.

On Tuesday, October 31, 2023, at the International Clinical Research Center within the Faculty Hospital St. Anne, the signing of a licensing agreement for the successful patent of a new technology for EKG devices took place. Through this step, the patent is transferred to the startup company VDI Technologies, s.r.o., which will advance the device for clinical use and subsequently bring it to the market. This move opens up new possibilities for physicians in the field of improved and more accurate diagnosis of heart diseases.

The new technology for devices commonly known by the acronym EKG has been developed for over ten years by a team of scientists from the International Clinical Research Center (ICRC) at St. Anne’s University Hospital, the 3rd Faculty of Medicine at Charles University, the Institute of Instrumentation of the Czech Academy of Sciences, and the company Cardion s.r.o. Representatives of these institutions signed a licensing agreement with the startup company VDI Technologies s.r.o. at the end of October for their high-frequency electrocardiogram (UHF-ECG) patent. With this, the startup gains rights to the new patent and can introduce the technology to the market. Currently, the company is taking steps towards the certification process, which is expected to obtain key approvals in the United States in 2024.

“This is a significant success, and I am pleased that, with the collaboration of so many institutions, we managed to sign a licensing agreement. The technology can now move closer to common use, with a significant contribution from the group around Associate Professor Čuril from the 3rd Faculty of Medicine at Charles University,” says Kateřina Šolcová, Business and Technology Director of Charles University Innovations Prague a.s.

The examination with the new technology is non-invasive for patients, as the method utilizes standard EKG electrodes and their regular clinical placement on the chest. The core of the technology lies in a new and compact evaluation unit developed jointly by all institutions. It provides physicians with unique information about the electrical activation of the heart chambers, which can help optimize surgical procedures and the setting of pacemakers in clinical practice. Even for patients with already implanted pacemakers, potential optimization means more efficient and gentler functioning towards the organism, allowing them to remain physically active for a longer time. In addition to improving the health of patients, the technology also simplifies the work for doctors. Results are available within minutes, and the electrical activation of the heart chambers is clearly visible on so-called depolarization maps. Furthermore, the technical solution is inexpensive and easily accessible.

“For us, this is a fundamental step,” says Miroslav Navrátil, CEO of the VDI Technologies startup. “We did something quite unconventional; we started working on the project even before obtaining the license. Our technology impressed investors so much that they were willing to take this risk with us,” he describes the journey. “But we all had great mutual trust,” he adds. “Bringing a new technology into commercial use is not a simple matter; signing the agreement is the culmination of many steps along a long journey. There is still a lot of work ahead of us. Colleagues from the startup are working on obtaining all necessary certifications,” adds Josef Lazar, Director of the Institute of Instrumentation of the Czech Academy of Sciences. However, for Czech scientists, this is already a tremendous success. They have received their second U.S. patent alongside numerous international awards for their innovative solution. “The startup consistently invests in research and development and prepares future innovations for the current technology,” state Pavel Jurák and Pavel Leinveber, researchers who contributed to the patented technology.

Irena Rektorová, the head of ICRC, thanked the scientists from ICRC and the Institute of Instrumentation of the Czech Academy of Sciences for the development of the new unique technology, the VDI company, and all partners for their patience and excellent cooperation. She wished the entire project much success and many interested parties worldwide. “The most important thing is that the new technology reaches the patients and contributes to improving care and the quality of their lives. ICRC fulfills its goal of bringing new discoveries to the patient and practicing cutting-edge medicine.”

 

All the awardees in one photo, source: Masaryk university

Within Masaryk University, approximately 200 graduates complete their doctoral studies annually. This year, for the third time, Vice-Rector for Research and Doctoral Studies, Šárka Pospíšilová, selected the best among them, who, along with their supervisors, received the Vice-Rector’s Award for outstanding achievements in their doctoral studies. We proudly announce that three of our supervisors were honored with this award, and two of the awarded doctoral graduates are already shaping the future of medicine with us at ICRC.

The awards were given to those who achieved highly significant research results included in their dissertation work. The conditions for receiving the award were twofold: a maximum study duration of 5 years and a first-author publication in a foreign journal within the first quartile, with the highest possible impact factor, a metric reflecting the quality of scientific publications.

For her dissertation research, which provided valuable insights into the early detection and therapy of heart failure in asymptomatic carriers of a specific type of muscular dystrophy gene, our physician and researcher Lucia Masárová, under the guidance of Roman Panovský, who leads the Noninvasive Cardiac Imaging team at ICRC, received the award.

Lucia Masárová and Roman Panovský with their award

“The topic was close to my heart because I know Duchenne muscular dystrophy from my childhood. In our village, we had a young boy with this condition, whom I knew from a very young age. We were classmates, and as children, we helped him when needed. I remember that in the first grade, he could still walk, but by the fifth grade, he was completely reliant on a wheelchair. I also knew his parents and understood the incredible sacrifice they made to provide him with the best 24-hour care, including operating artificial lung ventilation and other supportive devices,” reminisces Lucia. “I am even more delighted now to see boys with such disabilities in much better condition, thanks to advances in medicine, despite the fact that it remains an incurable disease.”

While all the care and attention were previously focused on severely handicapped boys, it is essential to regularly monitor their mothers from a cardiological perspective. “Until I started addressing this issue as part of my doctoral studies, I considered it a boys’ disease. However, from our research results, it is now clear that their mothers, the carriers of the genes, may not have severe muscular impairments, but they can develop cardiac issues, ranging from mild forms to the development of heart failure. We find similar ‘patterns’ in them as in boys,” she explains. “We continue to include new carriers of the DMD gene in our research, while also ensuring that all previously included carriers undergo regular echocardiographic examinations and magnetic resonance imaging of the heart,” adds Lucia Masárová. Her work was published in the Journal of the American College of Cardiology, and the impact factor of her work exceeded 10.

Kristína Mitterová and Irena Rektorová with their awards

Kristína Mitterová graduated from the Faculty of Medicine at Masaryk University, specializing in Neuroscience. In her doctoral studies, she focused on a dynamic approach to estimating cognitive reserve. “Cognitive reserve is the brain’s capacity to mitigate the effects of aging and accumulating pathological burdens. It contributes to the preservation of cognitive functions, and its reliable estimation serves to refine diagnosis and select suitable candidates for clinical interventions,” says Kristína Mitterová.

She also proposed the direction in which the selection of appropriate therapy for seniors can be guided, taking into account the size of cognitive reserve. She is among the core staff at CEITEC MU. Alongside Kristína, her supervisor Irena Rektorová, the head of ICRC and the leader of the Applied Neuroscience research group at CEITEC MU, also received the award.

Michaela Bartoňová and Ivan Rektor with their awards

The same program, Neuroscience, was also completed by the third awardee, Michaela Bartoňová. She successfully focused on advanced non-invasive methods for detecting pathological brain tissue in specific cases of focal epilepsy. She received the award along with her supervisor, Ivan Rektor, who is the head of the Center for Neuroscience at CEITEC MU and a physician at the 1st Neurological Clinic of the Faculty Hospital at St. Anne and the Faculty of Medicine at Masaryk University. “During her studies, Michaela published papers in excellent scientific journals, such as Nature Scientific Reports,” says Ivan Rektor about the awarded graduate.

This Sunday marks World Stroke Day, and on this occasion, the girls from the Public Health Group of our Stroke team set out into the corridors of St. Anne Hospital to support awareness of stroke prevention.

Prevention is free, and health is priceless. So, on Wednesday, October 25th, the Public Health Group led by Hana Maršálková demonstrated to patients at FNUSA how to unite against stroke. In the space near the hospital Café, visitors could experience the symptoms of a stroke firsthand, attempt to detect a stroke using CT scans, measure their blood pressure, or seek advice from an expert in healthy lifestyle. Of course, they also learned the basics of prevention, especially early recognition of stroke symptoms, and acquired the ability to react quickly.

Up to 80% of stroke cases can be prevented with proper care. Stroke affects one in four people during their lifetime, and one-third of all cases result in the patient’s death. Additionally, stroke is the most common cause of permanent disability. Immediate medical intervention significantly increases the chances of surviving a stroke without consequences.

“In the Czech Republic alone, approximately 25,000 people are affected by this condition each year, and only one-third of them fully recover. That’s why we focus on education in the field of prevention. With proper care for physical and mental health, up to 80% of cases could be prevented,” explains the head of the Public Health Group, Hana Maršálková.

Hana Maršálková, leader of Public Health Group

It is essential to recognize the key symptoms immediately

When suspecting a stroke, time is crucial. Both laypeople and experts use the so-called FAST method to recognize a stroke. Along with other important information on stroke prevention, the Public Health Group educated hospital visitors on this method. “The key is to know the three most common symptoms – a drooping corner of the mouth, sudden speech impairment, and weakening of the upper or lower limb on one side of the body,” lists the symptoms Professor Robert Mikulík, the head of the Cerebrovascular Research Team at FNUSA-ICRC. Once at least one of these three mentioned symptoms is recognized, it’s time to act, and it’s essential to call 155 or 112 immediately.

With her project, in which she investigated how to regenerate heart cells after a myocardial infarction, she won in the SANITAS – Life and Human Health category.

The award ceremony for the České hlavičky competition took place in the evening on Monday, October 16. The laureates were selected based on nominations by an expert jury composed of leading Czech scientists, including individuals such as Václav Hořejší, Jiří Grygar, and Zdeněk Kůs. Our student from the ICRC Academy, Kateřina Jiráková, received the award that evening.

She conducted her winning work titled “The Influence of Transcriptional Activity of the YAP1 Protein on the Expression of Cardiac Biomarkers in In Vitro Differentiated Cardiomyocytes” at the Center for Translational Medicine under the guidance of Vladimír Vinarský from the Mechanobiology of Diseases group.

Her work focuses on myocardial infarction. In her research, she explores how to initiate the regeneration of the adult heart by reactivating mechanosignaling pathways to enhance its post-infarction durability. “One possible way to kickstart the regeneration of the adult heart is the restoration of cardiomyocyte division. Cardiomyocyte division is activated during prenatal development by the YAP1 protein. Reactivating it in adult cardiomyocytes could potentially lead to renewed division and thus effective cardiac tissue regeneration,” she says about her work.

Katka’s work not only secured her first place in the České hlavičky competition but also earned her a place in the shortlist of the International High School Scientific Activities, which will take place in China. “We would like to wish her the best and hope she gets the opportunity to examine things up close,” adds Dr. Vinarský.

Katka is from Slavkov but is currently in her third year of studies at Gymnázium Brno, Kapitán Jaroš class. Following her initial internship at ICRC last year, she decided to continue with us and is currently working on tissue models of cardiomyocytes prepared from stem cells. “I am particularly interested in microscopy and automated image analysis using machine learning,” Katka describes.

The SANITAS category award within the České hlavičky project is given for scientific papers and projects in the field of natural sciences that deal with human health, biological and chemical processes contributing to the understanding of the human body’s function, or works and projects in virology, microbiology, biomedicine, and related disciplines, the results of which are relevant to human health.

Katka, congratulations from all of us at ICRC, and we hope that our collaboration will continue at least as well as it has so far!

At ICRC, we are not only actively involved in scientific research but also strive to improve education and increase health literacy among the general public. And where else to start than with children? In our country, heart attacks and strokes are among the leading causes of death. Our HOBIT program teaches schoolchildren to recognize the symptoms of these diseases and, importantly, how to take action. Its e-learning, including all materials and worksheets, is available online and completely free of charge.

Hana Maršálková, the leader of Program HOBIT

“HOdina BIologie pro živoT” in Czech language, “The Hour of Biology for Life” in English. HOBIT. A health education program that aims to teach elementary school students to recognize and respond appropriately to the symptoms of serious illnesses and conditions. It focuses primarily on the prevention of stroke and myocardial infarction but also educates children about other common diseases in our population, such as type 2 diabetes, obesity, panic disorder, Covid-19, and addiction.

“In 2009, research showed us that children in the second stage of elementary school know almost nothing about stroke, but they are interested in learning new information,” says Hana Maršálková, the head of the HOBIT program. “The ability to recognize its symptoms in a timely manner and take action is extremely important. Up to 80% of strokes can be prevented with the right prevention. However, if one does occur, it is crucial to get the affected person to the hospital as soon as possible to provide effective treatment. Therefore, the importance of health education is truly significant.”

The significance of the program is demonstrated not only by satisfied references from teachers and positive reactions from children but also by real results. Just a few months after the program was launched, two trained students successfully provided first aid on a man experiencing a heart attack.

The HOBIT program teaches children how to recognize the symptoms of a heart attack or stroke

Why teach children about stroke? Because by recognizing it early, they can save lives

“First aid for a stroke is truly simple, even a child can handle it,” continues Hana Maršálková. “The primary step is simply recognizing that something is happening. That’s what we mainly teach children as part of HOBIT.” Even though it may seem like the topic of stroke doesn’t concern children, unfortunately, the opposite is true. This condition can affect not only grandparents but also the generation of their parents. Although the average age of stroke patients is around 70 years, the number of younger patients is increasing worldwide.”

The Game of Life: Children themselves assess how to act

Video, worksheets, and a simulation test. HOBIT is a program prepared rigorously. In short videos, children will see real symptoms of stroke, heart attack, diabetes, and more. In the e-learning platform, worksheets and materials for group and homework are available. At home, children can refresh their knowledge with a mobile game, freely downloadable on Google Play and the App Store. The life-saving game can also be played through a web browser.

The child will decide whether it is necessary to call an ambulance during The HOBIT Program game

“We want to make it easier for teachers.”

The creators have endeavored to design the program so that teachers have as little trouble as possible when implementing it into their teaching. “Practically, all that’s needed is a good internet connection and their own headphones,” says Hana Maršálková. Students log into the e-learning platform with a nickname and a unified password, eliminating GDPR-related issues. Children don’t need to manage their own access credentials for the program. “So, there’s no risk of a teacher spending half a class dealing with forgotten passwords of children,” adds Hana Maršálková.

HIP HOP teaches children first aid

The creators of HOBIT are constantly expanding their horizons and draw inspiration for their program from abroad as well. One of the most interesting experiences for them was their contact with the New York project Hip Hop Public Health. It educates children from various locations in the USA on how to recognize the symptoms of a stroke, what the risk factors are, and how to prevent stroke, all through hip-hop. Expressing it through this musical genre is relatable to students. In an entertaining way, important information is conveyed.

The program in the USA, HIP HOP Public Health, teaches students about health through music

To remember the symptoms and know how to help

The goal of HOBIT is for children to remember this information in the long term, thus raising a health-literate generation. “Our vision is the widespread implementation of the program in Czech schools so that every child has the opportunity to learn this life-critical information,” adds Hanka Maršálková.

Under the leadership of Prof. Robert Mikulík, head of the Stroke Research Program at FNUSA-ICRC, and Prof. Natan Bornstein, Director of the Brain Division at Medical Center in Jerusalem, the Implementation Research Network in Stroke Care Quality (IRENE COST Action) has significantly contributed to the improvement of stroke care quality monitoring in Europe over the last 4.5 years. The primary goal of the IRENE COST Action was to create a strategy for measuring the quality of stroke care. As a result, Eastern European countries began to implement their own national strategies in this area.

Thanks to the IRENE COST Action, an international network was established, connecting more than 188 experts from 30 European and neighboring countries. This network has become a hub for knowledge sharing and collaboration in the field of stroke care.

The IRENE network also closely collaborated with global organizations such as the European Stroke Organisation and the ANGELS Initiative, aiding in the implementation of the Stroke Action Plan for Europe. This collaboration was evident during four major meetings held in Moldova, Armenia, the Czech Republic, and Croatia, all with the aim of improving care for stroke patients. In Moldova and Croatia, Professor Mikulík, the network leader, and others met with representatives of the local governments to discuss how to measure and enhance the quality of stroke care, following the example of the Czech Republic.

Additionally, thanks to the IRENE COST Action, 23 scientific missions were carried out, particularly for young researchers from Eastern Europe, with three of them hosted by the Stroke Research Team at FNUSA-ICRC. These missions served as a means to transfer new skills and methods in stroke treatment and promote collaboration among European institutions.

Within the project, eight young researchers from Poland, the Czech Republic, Croatia, Estonia, and Greece were given the opportunity to present their research at international conferences. Ph.D. students Sandra Thalerová and Ekaterina Volevach from the Stroke Research Team at FNUSA-ICRC received the chance and grant support to showcase their research projects in the development of new stroke treatments and prevention. Ekaterina Volevach, also undertook a month-long research mission at Maastricht University thanks to this project, where she learned new methods for developing effective public health interventions and co-authored a scientific paper with her mentor.

Although the IRENE COST Action has concluded, the community of engaged experts across Europe remains determined to continue their mission to improve stroke care.

Supported by the COST program (European Cooperation in Science and Technology), project number CA18118 – Implementation Research Network in Stroke Care Quality – IRENE.

A scientist as a boring nerd locked away among test tubes and beakers? Well, not at all! Science can be a real adventure. For the sixth year in a row, the Night of Scientists events have been trying to dispel myths about scientists. Hundreds of scientific institutions across the country participate to show visitors how science can be not only interesting and beneficial but, above all, fun.

This year, the Researches’ Night program revolved around the theme of Secrets, and our International Clinical Research Center couldn’t be absent. We guided the interested participants through places that an ordinary people wouldn’t typically visit and showcased the best of our work.

In the ICRC laboratories, there was a guided tour titled “The Secrets of Brain Stimulation.” What can science achieve today? For example, it can non-invasively stimulate central and peripheral nerves, meaning it can control one of the peripheral nerves without disrupting the body’s surface. In practice, this could remotely move a finger or tongue. And what’s the purpose of all this? Research is being conducted with the aim of treating not only neurological conditions like epilepsy but also conditions like obstructive sleep apnea. In the future, it may be possible to use this method to eliminate the symptoms of these diseases.

Team of the “Immune Adventure” tour

Enthusiasts of nocturnal exploration were also guided by scientific teams at the Biopark. There, the Center for Translational Medicine even prepared two tours. In the first one, titled “Immune Adventure: Uncover the Secrets of Your Inner Shield,” our scientists revealed to visitors how and with what our body can protect itself.

Mgr. Veronika Bosáková 

And also, what happens in the body when the immune system turns against ourselves. They even showcased a model of the intestines; testing on it in the future could contribute to the treatment of diseases such as Crohn’s disease. “When we test new drugs, we don’t have to use patients or animals,” explained researcher Veronika Bosáková to the visitors.

Mgr. Jan Frič, Ph.D. 

In the “Cells Under Pressure” program, visitors learned from representatives of the Mechanobiology in Disease team how cells perceive and respond to mechanical stimuli. Visitors were particularly intrigued by how armed with this information gathered from laboratory dishes, we can attempt to improve heart function after a heart attack or halt the spread of breast cancer. “By stretching heart cells in the dish, we model increased load after myocardial infarction to understand how to encourage the heart to endure longer,” summarized researcher Vladimír Vinarský.

Mgr. Bc. Vladimír Vinarský, Ph.D.

In summary, the Night of Scientists event was a resounding success! We garnered media attention, and just before the event kicked off, you could catch a live segment about us on CNN Prima News.

We had over 150 science and knowledge enthusiasts visit us, including those who are considering joining one of our teams as part of their professional journey. We wish them the best of luck and hope to see them on the premises of our International Center for Clinical Research in a few years.

The mission of Researches’ Night is to show the public that science is not a boring topic. On one day each year, scientific facilities across Europe open their doors to the public in the evening and night, offering guided tours, popular educational lectures, experiments, and workshops, all free of charge. Did you miss our program this year? Follow us on social media, and you’ll be the first to know when Night of Scientists 2024 is scheduled!

We want to express our gratitude to all who participated in Night of Scientists at ICRC and to everyone who visited us on Friday evening.

The Cellular and Molecular Immunoregulation (CMI) research team of the International Clinical Research Centre (ICRC) has been awarded a prestigious international HORIZON EUROPE grant. The project will focus on research into sepsis and septic shock, which affect up to 50 million people worldwide each year and account for almost 20% of global deaths. In addition, most surviving patients develop further complications that affect their quality of life. The total budget of the BEATsep project is €6.9 million.

This success is underlined by the fact that CMI-ICRC initiated the project, subsequently assembled a consortium of partners, and will act as coordinator of the project. This is only the third project in the Research and Innovation category focusing on population health to be coordinated from the Czech Republic. “The project is the result of our efforts over several years within the consortium, giving the chance to better understand and fundamentally change the recovery of paediatric and adult patients who have suffered septic shock. We would not have been able to develop this project without the intensive administrative support available to us at the ICRC,” added Dr. Jan Frič, head of the CMI.

The BEATsep project will use an interdisciplinary approach that will bring together research and clinical teams working on specific aspects of the development, treatment and prevention of the long-term consequences of sepsis and its impact on patients’ quality of life. Comprehensive clinical and research data generated during the project will be integrated using artificial intelligence algorithms into an easy-to-use predictive tool capable of identifying patients at highest risk of complications. Furthermore, the consortium plans to design a tertiary prevention strategy to help prevent the development of such outcomes.

To this end, a consortium has been formed to address this issue over the next five years. The consortium brings together renowned experts in immuno-metabolism, immunophenotyping, diagnostic sign research and several clinical teams caring for adult and paediatric sepsis patients. “It has taken nearly two years of intensive preparation and networking to assemble the consortium, which is already working on several joint projects.” says Dr. Marcela Hortová-Kohoutková from the CMI research group, who was instrumental in the project’s preparation.

In total, the BEATsep project coordinated by ICRC-FNUSA will involve 10 partners from 6 European countries including 1) CIML – Centre d’immunologie de Marseille-Luminy – (Aix-Marseille Université/CNRS/Inserm); 2) The Institute of Innate Immunity, at the Medical Faculty of the University of Bonn, Germany; 3) Faculty of Medicine at the Comenius University in Slovakia; 4) the Ludwig Boltzmann Institute for Traumatology, Vienna, Austria; 5) BioVariance GmbH, Germany; 6) Masaryk University, Brno, Czechia; 7) National Institute of Health, Prague, Czechia; 8) University of Galway and 9) APHM – Marseille Hospitals. BEATsep will bring together renowned experts in immunometabolism, epigenetics, immunophenotyping, diagnostic research and several clinical teams caring for paediatric and adult sepsis patients. “The BEATsep project is an example of an innovative and successful combination of translational and clinical research, the know-how of our own and international scientists, and collaboration between hospitals, universities and other scientific institutions of renown. I am proud that the coordinating team is from the ICRC, a joint department of St. Anne’s University Hospital and the Faculty of Medicine of Masaryk University in Brno,” said Prof. Irena Rektorova, M.D., Head of the ICRC.

Consortium map

For more information and updates @BEATsepsis (Twitter, X), www.beatsepsis.eu, LinkedIN

The International Clinical Research Centre (ICRC) is a joint facility of St. Anne’s University Hospital in Brno and the Faculty of Medicine of Masaryk University.

He works in the Protein Engineering ICRC research team at the Loschmidt Laboratories, Faculty of Science, MU. In 2020, he was awarded a Fulbright Scholarship to spend a semester at the University of Texas at Austin in the group of Prof. Kenneth A. Johnson. This year he successfully defended his PhD in Molecular and Cell Biology and Genetics. For his thesis on “Rational protein design guided by kinetic studies” he received the MU Rector’s Award. He repeated his success from 2018, when he was awarded the same prize for outstanding results in his Master’s studies. In the interview, he describes his scientific beginnings and his successes in researching “glowing” enzymes or stroke drugs.

Photo: RNDr. Martin Toul, Ph.D.

Photo: RNDr. Martin Toul, Ph.D.

What was your path to science?

I think that every young child has a kind of scientific or exploratory spirit in him, as he/she discovers the world around little by little. Not every such spirit, however, survives into adulthood. For me, this interest persisted, which is actually the reason why I took the path of science. Thanks to my older sister and her school notes, I was interested in chemistry from about the second grade of elementary school – I loved learning the names of chemical elements, filling in their names in crossword puzzles, and looked forward to taking this subject in school as well. Although I also enjoyed math and physics, chemistry always led the way. So, when choosing a college, my direction was quite clear. Interestingly, perhaps, I never had a very positive relationship with biology and only got more in depth with it by choosing the Biochemistry program, as I saw more potential in connecting chemical research with living nature. In the end, it turned out that while the areas of animal and plant biology discussed in elementary and high school were never really likely to excite me much, the microworld at the level of biomolecules, DNA and proteins, was where I came into my own. Thus, my current research combines biology with chemistry, as well as physics and mathematics, so I am doing exactly what fulfils me the most.

What exactly are you researching?

In our research group at Loschmidt Laboratories, we are generally involved in protein engineering. This means that we specifically modify a protein to exhibit improved properties or to get rid of unwanted side effects for more effective use in practice. In fact, proteins find a variety of applications, whether as drugs in clinical practice, components in diagnostic kits, or reagents for the production of important materials in biotechnology. Thanks to protein engineering, we can improve the efficiency of these molecules, their heat resistance, or even the selectivity of a given process, to make their use in practice and industry real. I am specifically focusing on, among others, two important groups of proteins. The first group is thrombolytics, used as drugs to dissolve blood clots in stroke or myocardial infarction. The second group are luciferases, bioluminescent “glowing” enzymes that are used in diagnostic kits but could also serve as an alternative source of glow in the future. However, all of these proteins suffer from certain weaknesses that need to be addressed for them to perform their role truly effectively for their intended purpose. And that is what protein engineering modifications are designed to do.

What was your PhD thesis about?

My PhD thesis focused on the use of advanced kinetic methods to reveal the major weaknesses of the proteins studied and their subsequent removal. The biggest stumbling block in protein engineering is that, in the case of imperfect proteins, we don’t initially know exactly what needs to be changed and improved about them to make them more effective for a given purpose. And it is detailed kinetic analysis that is one of the tools to uncover the precise mechanism of how proteins work at the molecular level, and also to identify which step of this mechanism is the so-called limiting step. This allows us to specifically target this major weakness and make targeted adjustments, greatly increasing the chances of successfully improving the protein rather than if we were to randomly adjust it “blindly”. By this strategy, we have been able to create, for example, a modified thrombolytic with the potential to exhibit a reduced risk of bleeding after administration, or an improved luciferase with a 100-fold increase in luminescence for long-term emission of bioluminescent light.

How would you explain the benefits of your research to a non-scientific audience?  

In the thrombolytic protein project mentioned above, we want to improve the current stroke drug and develop something more effective that could save many patients around the world. Nearly 18 million people die from cardiovascular disease (largely myocardial infarction and stroke) every year, which is a terrifying number, so the motivation is huge. As for research into the luminous enzyme luciferase, there are several possibilities. In diagnostic practice, luciferases are widely used to detect various biomarkers (i.e. measurable indicators) of disease, so improving them will allow us to make this detection even more efficient and sensitive, or to extend it to capture other important substances. Outside of clinical practice, there is then huge potential to use luciferases as an alternative light source to conventional lamps. With a system based on biomolecules, such illumination could be fully renewable and sustainable.

Did your time at the ICRC contribute to your success?

Definitely. The connection of our research group to the ICRC was crucial. It has given us access to clinically oriented projects that are very attractive and bring a specific application potential to our lives. At the same time, thanks to the ICRC, we were able to create a large consortium STROKE Brno, which brings together experts from many fields. This takes our stroke research to a much higher level and allows us not to stop researching only at the level of a scientific paper, but to try to take a possible new drug to the next stages of testing. As part of the collaboration, it can be tested on real human blood clots and also in vivo in animal models to see if it is indeed an attractive candidate before possible clinical testing. As a result of the connection to the doctors at FNUSA, we are also assured that the research is moving in the right direction and that we are not trying to improve something in laboratory conditions that no doctor will use in practice anyway.

What are your future plans?

I have just finished my PhD, so I am looking forward to moving into new and interesting scientific areas to broaden my horizons and learn something new. I am now heading for a postdoctoral position abroad. I went through several interviews and finally decided on a position at the Belgian VIB institute, which will fulfil my future plans in the next few years. Subsequently, my current vision is that I would like to return to the Czech Republic and do my own research in academia here. However, I am open to different opportunities, so maybe it will turn out differently and I will end up in another country or a biotech company. Who knows?! In any case, I would like to stay in a scientific environment and continue to explore the unexplored.

Thank you for the interview and I wish you continued success in your research.

 

Author: Marta Vrlová, M.A., MPH, Senior PR Specialist ICRC, marta.vrlova@fnusa.cz.

Media contact: Ing. Jiří Erlebach, Head of PR and Marketing Dpt, FNUSA Spokesperson, +420 543 182 006, jiri.erlebach@fnusa.cz.