On 25th May 2021, Alliance4Life organizes the kick-off meeting of its new Horizon 2020 project titled Alliance for Life Sciences: From Strategies to Actions in Central and Eastern Europe (A4L_ACTIONS).

It is a continuation of the successful Alliance4Life project, which was initiated by the CEITEC Masaryk University institute with a clear mission to help bridge the innovation gap between Western and Eastern Europe. The ten founding members, including our center, formed the alliance as a permanent structure in Vilnius in October 2019 with the signing of a Memorandum of Understanding and continued to work together in a difficult year 2020. Two new member institutions from Bulgaria and Romania were invited to the A4L_ACTIONS project.

A4L ACTIONS aims to increase the attractiveness of science centers in Central and Eastern Europe for cooperation with Western Europe, which will have an impact on Europe-wide research excellence and the impact of scientific research on society, human health and quality of life. A4L ACTIONS builds on the results achieved under A4L and will seek to further develop them in the following areas:
– Culture fostering excellence: piloting peer-evaluation and assessment of institutional practice as a strategic management tool, professionalizing research administration;
– Recognition and trust towards CEE: attracting advanced partners to identified pockets of excellence, supporting scientific ideas originating in CEE, initiating new international projects and collaborations with industry;
– Career policy nurturing talent: training and networking next generation of leaders, upgrading institutional career systems;
– Impact on innovation: raising the competences of Technology Transfer specialists, creating industry relations platform linking academia and industry;
– Spill-over effects: sharing, inspiring, communicating with stakeholders and policy makers; using the established networks to gain advice, new collaborations and EU-wide impact.

The plenary session will be open to all, registration is possible here:

A4L_Leaflet1    A4L_Leaflet2

From 2016 to 2020 the International Clinical Research Center at St. Anne’s University Hospital Brno (FNUSA-ICRC) was financed mainly from the National Sustainability Program (the NPU II project). At the end of this period, a final evaluation took place, where members of the opponent board from the Ministry of Education, Youth and Sports together with opponents from numerous other prestigious foreign institutions evaluated the project as excellent and with an international impact. FNUSA-ICRC´s scientists thus met the goals set by the contract and achieved excellent, internationally recognized results.

Within five years, FNUSA-ICRC has received subsidies from the NPU II project with the total amount of CZK 985 million. The final report states that the Center has made significant progress towards being an internationally competitive and sustainable, multidisciplinary center of excellence in translational medicine. Both in clinical and basic research.

The final report emphasizes, inter alia, that in 2020, FNUSA-ICRC continued to develop despite the unusual and unpredictable situation associated with COVID-19. “It should be noted that we had to restrict access to laboratories, and many scientists, nurses as well as administrators devoted their time to helping patients, working in test centers or supporting other hospital services,” said Pavel Iványi, MBA, LL.M., CEO of the Center. “That is why I think we´re talking about an extraordinary result and I thank everyone who made a contribution.”

In addition to all commitments being fulfilled and results achieved, the Board of Opponents also highlighted FNUSA-ICRC´s support of mobility (supporting students and enabling them to acquire new abilities, knowledge and skills) – 943 students from all over the world took part in the project and positively acknowledged the cooperation, for example in the form of joint grants. The number of implemented clinical trials is also exceptional, mainly because FNUSA-ICRC is the only so-called Prime Site in the Czech Republic for the global IQVIA group. Just to give an idea – there are currently 170 clinical trials in progress.

Many scientific outputs of FNUSA-ICRC have been published in leading international journals and are considered key in their respective scientific fields. For example, several articles appeared in the Top 10 ranking scientific journals, an average of 17% of the total number of FNUSA-ICRC´s publications to be exact and an average of 8% appeared in the Top 5. FNUSA-ICRC researchers have published their articles in Nature, New England Journal of Medicine, Lancet Neurology, Nature Reviews Neurology, etc.

The evaluation report also contains several recommendations for the future. In particular, greater deepening of cooperation in the international field, with domestic universities, and a continued involvement of students in scientific projects. “We are aware of all these challenges and we are working on them. For example, we are negotiating with Masaryk University to deepen our cooperation,“ said director Iványi. “We are also trying to fine-tune the funding system with our founder, the Ministry of Health, so that we can ensure certainty of function for already established international scientific teams and the Center itself.”

The main goal of the NPU II project was to enable FNUSA-ICRC to develop its existing scientific potential in basic, translational and clinical research. Especially focusing on fields of cardiovascular, neuroscience and oncological research, medical biology, biomedical engineering, molecular biology and stem cells. A clear advantage is the connection to St. Anne’s University Hospital Brno, which provides direct access to a large demographic of patients. This creates optimal conditions for translational medical research, focusing on various diseases (including cardiac arrhythmias, heart failure, sleep disorders, stroke, dementia and cancer).

FNUSA-ICRC_Building    FNUSA-ICRC_Research

Feeling lonely, worried about the health of their loved ones and stress from an unstable situation. The pandemic of the COVID-19 disease affected not only the physical health of the population, but also the mental health, which has now been confirmed by research in which researchers from the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC) and the American Mayo Clinic.

The researchers analyzed the impact of the pandemic and related restrictive measures on mental health in the participants of the Kardiovize project, a study that has been examining the local level of health for a long time on a population sample of one percent of the city of Brno. 715 Brno residents took part in the analysis of changes in mental health during the first hard lockdown in the spring of 2020, when, in addition to services, the borders of the Czech Republic were closed. “The results showed that the incidence of increased stress and depressive symptoms increased 1.4 to 5.5times compared to the period before the COVID-19 pandemic,” said PhDr. Jan Sebastian Novotný, Ph.D., first author of an international study and member of the Translational Neuroscience and Aging Program Research group FNUSA-ICRC. “This deterioration manifested itself in all age groups and was more pronounced in women,” he added.

The study also showed that, despite a comparable deterioration in all age groups during the pandemic, younger grades suffered more mentally, which may be due to work or study insecurity, and thus financial instability. At the same time, richer life experiences and lower expectations can be expected for older age groups, which also contributes to higher mental resilience in general. The main risk factors for deteriorating mental health have been feelings of loneliness, perceptions of COVID-19 as threatening, and some negative effects on lifestyle – such as the financial effects of restrictive measures, lack of exercise or deterioration in sleep quality. On the contrary, a higher level of resilience, ie the ability to maintain a standard level of functioning despite adverse circumstances, proved to be a protective factor.

“The observed increase in the incidence of stress and depressive symptoms as well as many identified risk factors can be prevented, diagnosed and treated. It is therefore necessary to respond to these findings in a timely and targeted manner by setting up appropriate psychological and psychiatric help so as to reduce the risk of a subsequent pandemic of mental disorders in the population, “said Jan Sebastian Novotný.

The FNUSA-ICRC research team continues the study, its goal is to capture the long-term effects on the mental health of Brno residents.

Novotny

Myeloid derived suppressor cells (MDSC) are heterogenic populations of cells that, due to their suppressive activity, negatively affect the body’s immune response during inflammation, infections, but also after transplants or in oncological diseases. The role of these cells in sepsis, popularly called blood poisoning, was the focus of the Cellular and Molecular Immunoregulation research team of the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC).

Animal models have shown that myeloid derived suppressor cells are important regulators of immune processes during sepsis. However, in humans, confirming of these observations has been very challenging, especially due to the lack of clearly defined preparation protocols and phenotypic schemes for diverse subsets of these cells. Our researchers focused on the use of flow cytometry together with mathematical models to more accurately determine the role of MDSC during sepsis. “Using this method, we combined complex phenotyping with mathematical algorithm for unsupervised clustering using self-organizing maps to identify three recently defined subsets of human MDSCs,” explained Marco De Zuani Ph.D. MSc., the first author of the work.

Twelve patients affected by septic shock and nine healthy individuals participated in the study. The expansion of two types of human MDSCs was demonstrated during the early phase of sepsis, and high levels of PMN-MDSCs were present many months after discharge from the hospital, suggesting a role for these cells in the later health complications associated with sepsis. “The data from this study suggest that the expansion of these cells could be responsible for the high mortality observed in patients who survived septic shock,” said Dr. De Zuani.

Targeted treatment of MDSCs could thus improve patients’ quality of life after sepsis. However, this is not the only result of this work. The combined use of flow cytometry and so-called metaclustering algorithms enables the rapid identification of various immune cells not only in the laboratory but also in the clinical environment, which might have great potential for future screening and diagnosic applications.

You can find the article here:

DeZuani

Let’s stop the world together for a moment and take a closer look at what life looks like second by second when the stroke decides to turn it upside down. Together with experts in cerebrovascular research and rehabilitation care, during the webinar we compile a comprehensive picture of the path that a person affected by a stroke goes through and fill in all the unknowns
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Stroke is one of the most common causes of death and permanent disability in our country. But what exactly does it look like when it strikes? Why never go to the hospital alone? How can the brain be rehabilitated and what will the insurance company pay for the patients? You will also find the answer to these topics. You can ask further questions also during the webinar.

Tune in to the webinar on 15 May at 5 pm and find out how patients live after a stroke, how the consequences affect the lives of patients and caring families, and how you can take care of a loved one after a stroke yourself.

Jan Bobek from the FNUSA-ICRC Cerebrovascular Research Program and physiotherapist Tereza Valíková from the SAREMA Rehabilitation Center will guide you through the topic.

Leaflet_CMP

The Molecular, Cellular and Clinical Approach to Healthy Aging (ENOCH) project focuses on finding treatment for the diseases that most affect aging, such as dementia, cancer and heart disease. Five scientific centers in Moravia cooperate on it, in addition to our center it is the Institute of Molecular and Translational Medicine of Palacký University in Olomouc, RECAMO center of the Masaryk memorial Cancer Institute, the Department of Neurology of the Medical Faculty of Olomouc University Hospital and Blood Cancer Research Group at the University of Ostrava.

The first meeting of all twenty FNUSA-ICRC research teams participating in this project took place on Thursday, April 8. This is two thirds of all teams within our center, so the ENOCH project is given a lot of attention. The course of the meeting also corresponded to this, the program mainly included information on the status of fulfillment of individual tasks and mutual cooperation within the FNUSA-ICRC.

The results of the online meeting were then entirely positive. Meeting the individual milestones of the project should be smooth and there has been a big step forward in the area of research quality. It was also stated that due to the state of work on the ENOCH project, in the future our center could try to apply for a similarly significant grant in cooperation with domestic or foreign research centers. The next meeting should be at the end of June.

Supported by the European Regional Development Fund – Project ENOCH (No. CZ.02.1.01/0.0/0.0/16_019/0000868).
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New publication of the Kardiovize research team of the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC) deals with visceral fat, ie body fat that is stored around vital organs. “This is the first published study conducted in Central and Eastern Europe,” said Dr. Juan Pablo Gonzalez Rivas, Principal Investigator of Kardiovize team. “It turned out that we can’t use the values of visceral fat defined by colleagues in the USA or Japan to determine cardiovascular risk. The local population has very different values. ” The publication was published in the journal Obesity Research & Clinical Practice and can be found here:

A young researcher, Anna Polcrová, who studied Nutritional Therapy at the Faculty of Medicine of Masaryk University, Social Epidemiology at the Faculty of Science of Charles University and continued her studies at the Masaryk University while working in Kardiovize team. We asked her for a detailed explanation of not only the results of the study:

It is very well known that obesity is dangerous for the health, but it is not common to talk about visceral fat. What is visceral fat? And why is unhealthy?
The body fat can be stored in various areas. We basically distinguish between subcutaneous fat, which is located under the skin, and visceral fat, which is located inside abdominal area and surrounding our organs. The location of fat depot significantly affects its impact on our health. Previous research determined that a subcutaneously located fat depot is not as risky as visceral fat, because excess of visceral fat is related to more metabolic abnormalities, including insulin resistance, type 2 diabetes mellitus, increased risk of thrombosis, or endothelial dysfunction.

How can be measured visceral fat? How do I know that if I have too much?
The gold standard method to measure visceral fat is computed tomography, but this is relatively expensive and exposes individuals to radiation. We can use bioelectrical impedance analysis, which is an advantageous method because it is simple, quick, low cost, non-invasiveness, and showed strong correlation with values measured by computed tomography. Bioimpedance is based on weak electricity flowing through the body and the voltage is measured in order to calculate impedance (resistance), allowing to determine the body composition, including visceral fat area. Although it may sound dangerous, this method is completely painless and can be used for people of any age. The only contraindication is the presence of a pacemaker or pregnancy. High amount of visceral fat is unhealthy, commonly used devices in Czechia use a cut-off of 100 cm2 to define high amount of visceral fat, however, this value came from Asian studies, that does not distinguish between genders, and has not been validated in the European population.

What is the main result of your study? And how this can benefit the European population?
Our results showed that the cut-offs of visceral fat related to cardiometabolic risk in the Czech population are different in comparison to previous studies in different populations. We observed that cut-offs of 90 cm2 for men and 109 cm2 for women were associated with the presence of cardiometabolic risk factors including high waist circumference, elevated blood pressure, reduced HDL-cholesterol, elevated triglycerides, and impaired fasting glucose. Men showed a higher risk of cardiometabolic complication in lower values of visceral fat in comparison to women. In summary, the distinguishment of the high and low level of visceral fat and related cardiometabolic risk need to be based on cut-offs determined for a specific population, respecting gender differences.

You now have one year working with the Kardiovize team, how has been the experience working with them in ICRC? What have your learned?
I am very happy about the opportunity to work in the Kardiovize team. This team is open to share their experience and support junior researchers. Over the past 12 months, I have published 3 articles (1 as a first author), collaborated in a grant proposal, and we are working on an intervention to reduce the cardiometabolic risk of people from Brno with a lifestyle program. Moreover, thanks to my experience in Kardiovize, I started to study Ph.D. program in Environmental health sciences at RECETOX in Masaryk University. This combination is creating an amazing space for me to further develop my research in the fields of my passion – lifestyle, health literacy, and social determinants of health.

Jan Mičan became one of the holders of this year’s Dean’s Award of the Faculty of Medicine, Masaryk University for the best undergraduate students of the faculty. He received it in the Category for outstanding scientific performance, where he took first place. The Dean’s Award is given according to more selective criteria than in previous years – obtaining it is really a very prestigious matter. Jan Mičan is part of the Protein Engineering team of the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC), where, according to the team leader prof. Damborsky was literally raised up. In the Loschmidt laboratories of the Faculty of Science, Masaryk University and the FNUSA-ICRC, he focuses, for example, on the development of new thrombolytics within the Stroke Brno platform.

Congratulations to the Dean’s Award of the Faculty of Medicine, Masaryk University and the first place in the Category for excellent scientific performance. Was it a specific scientific performance or was it an award for a comprehensive work?
It is an award for the overall work, Professor Damborský and I have filled in a number of scientific publications in which I participated. These were, for example, publications from my very first research, which dealt with the development of enzymes for the decomposition of mustard gas. At that time, we developed more efficient enzymes to neutralize this war gas instead of using strong caustics or combustibles, which cannot be used, for example, after some expensive equipment or vehicles are hitted. A number of publications were also from research dealing with the development of new thrombolytics, ie drugs for dissolving blood clots, which we do in cooperation with Professor Mikulík within the Stroke Brno project.

You work in Loschmidt Laboratories of Faculty of Science, Masaryk University and FNUSA-ICRC. Was it your long-term career goal or is it a coincidence?
I would say that it was a coincidence… I met Loschmidt’s laboratories at the grammar school, where I noticed a leaflet that attracted students to the Summer School of Protein Engineering event (this year, June 28-30 https://loschmidt.chemi.muni.cz/school/ ed. note). The scientific environment and science in general have always attracted me a lot, and the event promised to get acquainted with the issues of protein engineering directly in laboratories. I applied, I was selected and I was really interested. After high school, I got to FM MU, and that’s where my hesitation between medicine and science began, which actually lasts to this day. I managed to get into biochemistry and medicine and I couldn’t decide what would be better. Fortunately, I managed to get into the P-PooL program (Undergraduate Program for motivated medical students with extended scientific training), in which I was able to do science from the first year of medicine. I was placed behind the 150th place on the receivers, which would normally close the door to P-PooL, but thanks to the saying ” Nothing is lost for asking ” and many emails, I was included in the selection procedure and fortunately I was selected later. When I had to choose a project in the first year, I remembered my stay in Loschmidt’s laboratories and wrote prof. Damborsky and Dr. Bednar, if they don’t have one. We agreed to start computational research – first these were the already mentioned enzymes for the decomposition of mustard gas. Although the project was not completed, because we were unable to create a better enzyme than those used now, I have learned the extreme number of different methods and procedures that I have used so far. I remember the beginning of the cooperation on the development of thrombolytics exactly, it was the day after the anatomy test, when I was able to attend the meeting of the team members, and I was offered if I did not want to work with the Stroke Research team and prof. Mikulík. So really a coincidence.

What do you plan after studying and what is the specific scope of your work?
When I graduate, I will be a general practitioner, I will specialize only in the attestation. I would very much like to work at a neurological clinic, where patients are treated and recovering after a stroke, but also with other neurological diseases, that is my goal. After I started doing stroke research, my grandmother died of it, so I have unresolved bills with the stroke… I’m still slightly hesitant to be a doctor and stay with research, but now the scales are inclined to work as a doctor, but certainly with research I will stay in the hospital.
When it comes to research, 98 percent of the time it’s computer work. Either on mine or I use supercomputers everywhere in the country and around the world. I am a member of the Metacentrum organization, which enables this in the Czech Republic. There are times when I use, for example, a thousand computers at once, to calculate complex chemical reactions or to process statistical data on genetic or protein sequences from all possible animals and protein variants that exist in nature, when I try to find various useful connections between them. I also worked in the laboratory when I tested the enzymes I developed for the decomposition of mustard gas. I wanted to try it and learn techniques like protein purification, cultivation in bacteria, genetic modification of bacteria… I spent the whole summer and winter on it, but I wouldn’t change it for computer work… There, if something goes wrong, then follow the steps you can find and fix a bug in the program, while in that lab you sometimes don’t know what and why it went wrong. That life is simply unpredictable and even though we know a lot about it, it is still not enough… To do that, you have to sit it down, weld it, wash it off, dose it, stir it up. Computational biology and chemistry, on the other hand, are purely creative work, and if you don’t like to do something a third time, you write a program and it will do it for you. And with an internet connection, you can do it, for example, from the Jeseníky Mountains.
Then I dealt with the issue of thrombolytics for a really long time, a number of new drug candidates emerged from the research. Now it is up to colleagues from the Veterinary Research Institute in Brno or the Institute of Biophysics of the AV CR to test them on animal and fluid models. Specifically, there are eleven new enzymes (so-called Ocean’s eleven) with different properties and approaches to the treatment of stroke and four thrombolytics based on staphylokinase, which I developed in Israel. Of course, I pay close attention to how the tests are evolving, but now I am fully committed to finding enzymes for more efficient degradation of plastics for industrial and environmental purposes. If successful, this would be a new way of recycling, which would help to make more and cheaper use of recycled plastics. I also now have several other strategies to further improve thrombolytics by analyzing coevolution or modeling the interaction with fibrin, so hopefully there will be time for them later, I’m looking forward to it.

Do staphylokinases have anything to do with the dreaded staphylococci?
Yes, we try to take advantage of the unique properties of these bacteria. Staphylokinase is a substance with which staphylococci literally make their way through the human body. The defenses that every person has try to stop their progress by using fibrin barriers that build around the bacteria. However, staphylococci can dissolve these clots with the enzyme staphylokinase, and this is exactly what we want to use in the treatment.

What are your other goals? What is the scientific holy grail you would like to achieve for you?
So this is probably the hardest question I’ve ever had… Of course, I would like to develop a new universal remedy for ischemic stroke, myocardial infarction and embolism in general – everything is caused by blood clots… But the Holy Grail is something else for me, I imagine it like it as an effective interconnection of various scientific disciplines and disciplines. For example, medicine, biochemistry, computer technology, data visualization… All this can be beautifully put together in medical practice and I am terribly fascinated by it. I would like to somehow blur the boundaries between these fields and find new uses for their interconnection. For example, using biochemical methods, develop a new drug, get it to the pediatric patient’s bedside, and then compile an effective visually comprehensible treatment plan to understand what is happening to it and why doctors are doing what they are doing with it. And that will calm him down and allow him to manage his diagnosis and treatment well.
Another thing that I am very interested in is from the field of computational-chemical, it is the breaking of the so-called Anfinsen’s dogma (This hypothesis states that, at least for small spherical proteins, the native structure of the proteins is determined only by the amino acid sequence. In the environmental conditions in which association occurs, the original structure is unique, stable and kinetically with minimal free energy. Three conditions apply to this: 1. Uniqueness – requires that the sequence has no other possibilities of comparable free energy, therefore the free energy must be unique. small changes in the environment cannot lead to changes in the model with the minimum possible free energy 3. Kinetic availability – means that the bond on the surface with free energy from uncoupled to associated must be sufficiently balanced. shape ed. note). It is a question of what those proteins actually look like, how we all de facto look on this microscopic scale. The standard protein has about 300 amino acids, of which there are twenty species. There are astronomical numbers of those combinations, here 20 to three hundred, which is a huge number, more than there are atoms in the universe. But how and according to which laws is it put together? Google’s AlphaFold2 project, which is now much talked about, is a great hope for solving this problem. It is based on machine learning, which is extremely complex in itself, machines sometimes learn completely on their own, combine different properties, so-called properties and metaproperties, but the weakness is the lack of intelligibility for humans – the project may tell us that some sequence amino acids fold into exactly this shape – a protein, which is extremely useful, but it does not create a theory that one can understand. And that’s exactly what I want. Understanding how proteins are put together.

Now that we’re interested in interdisciplinary collaboration – the media has recently said that physicists are on the verge of finding the fifth fundamental force in the universe – this also interests you, could it help in the field of biochemistry or machine learning and artificial intelligence?
This probably doesn’t upset me, given that this force is so “strong” that we had to create a special accelerator in which we observe muons, particles smaller than atoms, and only then were we able to notice it… If it were to be a force that should have some significance in biochemistry, for example, would not escape us for so long. I don’t think this will affect much in the medical world. Although the human body can perceive quantum effects with the basic senses – for example, you will know the difference between water and heavy water, which has a neutron more by taste, but this is extreme and this new force will probably have no effect. But I have heard that this discovery could fundamentally change communication between people and allow very fast transmission of information. And this could significantly improve the calculations and thus the machine learning.

Do you have any free time left in your work? If so, then how do you like to spend it the most?
I like to spend my free time outside, thank God the weather is a bit more acceptable, so it will be even more intense again. Sometimes it’s “just” walks or trips, I would like to invite you to the shores of Svitava, where we or our friends do such improvised guitar concerts. I also really like such more special walks, it’s called urban exploration and it’s a visit to old abandoned buildings created by human activity, which are somehow forgotten, unused, intended for demolition and at the same time interesting and beautiful. It’s on the edge and I don’t encourage anyone else to do it, but I don’t do any destructive or harmful activities there, it’s just about discovering places that are connected with the history of this or that place.
I will not report it anywhere and thank you for the interview!

Non-alcoholic fatty liver disease (NAFLD) is a disease in which fat accumulates in the liver without excessive alcohol consumption. It is related, among other things, to the development of diabetes II. type, obesity and also genetic predisposition and is therefore an increasingly common diagnosis. It is estimated that more than a quarter of the world’s population suffers from NAFLD.

An international research team, whose members were also scientists from The International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC), focused in its work on how NAFLD is affected by genetic variations. Their article entitled “Pediatric Non-Alcoholic Fatty Liver Disease is Affected by Genetic Variants Involved in Lifespan / Healthspan” was published in the Journal of Pediatric Gastroenterology and Nutrition.

“We investigated the impact of single nucleotide polymorphisms (SNPs), which are related to lifespan,” said Manlio Vinciguerra, Ph.D. MSc, Principal Investigatorof Epigenetics, Metabolism and Aging research team of FNUSA-ICRC. Single nucleotide polymorphisms are variations in a single nucleotide in the human genome and are the basis of differences in our susceptibility to various diseases.

The research was performed on a sample of 177 patients with this diagnosis with an average age of 13.7 years. As a control, there were 146 healthy individuals. 10 single nucleotide polymorphism were selected, which are demonstrably related to metabolism and also to liver function. “We used multidimensional reduction analysis and control of SNP-SNP interactions on the obtained samples in order to identify the effect of the examined SNPs in the prediction of NAFLD and related complications,” described Dr. Vinciguerra.

The results showed that all examined SNPs are related to individual metabolic features of NAFLD, however, none was significantly associated with its diagnosis. Subsequent testing of potential synergies revealed that the combination of IL-6 rs1800795 and ANRIL rs1556516 could be used to diagnose NAFLD and to estimate their life expectancy. “To confirm whether the genetic interaction between the two genes affects the development of this disease in children, another, larger, study will be needed,” added Dr. Vinciguerra.

You can find the article here:

At the beginning of March, the University of Cape Town organized a workshop called CCP4 Crystallographic School in South Africa. Due to the current situation, it was of course in the online environment and Ing. Andrea Schenkmayerová Ph.D. from Loschmidt laboratories of Faculty of Science MU and the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC) achieved great success. The researcher of the Protein Engineering reserach team won the award for the best poster entitled Structural analysis of a haloalkane dehalogenase from subfamily HLD-III.

In general, crystallography is a scientific discipline that deals primarily with the study of the arrangement and bonding of atoms in crystals and the study of the geometric structure of crystal lattices. Although most of us imagine a crystal such as a grain of salt, the modern concept of a crystal is based directly on the characteristics of the internal structure at the level of atoms and not on its external shape. The crystalline state of matter is more energetically advantageous and at present we can get not only minerals but also metal alloys or organic molecules into this state. The importance of crystallography is also underlined by the fact that 32 Nobel Prizes have so far been awarded for research and related results.

Macromolecular crystallography deals with the study of the structure and spatial arrangement of biological macromolecules (eg proteins, DNA) and their complexes, which is key to understanding their function in organisms. A detailed understanding of the structure and function of biological macromolecules is then key to understanding complex cellular processes, their homeostasis but also their pathological manifestations.

Crystallography is also used to research new proteins and their inhibitors, which could be used, for example, as drugs. The therapeutic effect is influenced, inter alia, by the shape of the molecules of the therapeutic component, so that crystallography functions here as a tool for obtaining information about the shape of the molecules. However, we would not find a classic optical microscope in this area, the light has too long wavelength – for microscopy at the molecular level devices using for example, X-rays. In general, the best drug is one whose molecule fits into a suitable binding site in the macromolecule and thus affects its biological activity.

Ing. Andrea Schenkmayerová Ph.D. in her work focused on hitherto structurally unexplored enzymes from the haloalkane dehalogenase family. These enzymes have an interesting property – they catalyze the cleavage of carbon-halogen bonds to form the corresponding alcohol, halogen anion and proton. Due to these properties, these enzymes are used in various biotechnological applications. In addition to haloalkane dehalogenase activity, lactone decarboxylase activity has been found in some of these enzymes in recent years, prompting a broad scientific discussion of the natural biological function of these enzymes and how they evolved during evolution.

“It was started by my colleague Ing. Klaudia Chmelová and after she left for maternity, I started doing it, “said Schenkmayerová. “It was a real challenge, because so far no one in the world has been able to determine the structure of the enzyme from the HLD-III subgroup, because it forms heterogeneous oligomeric structures, which makes their structural analysis very impossible. In our laboratory, systematic work has succeeded in developing a method by which we are able to prepare relatively homogeneous enzyme preparations, which opened the way for their structural analysis using cryo-electron microscopy and X-ray crystallography. Although we eventually managed to prepare crystals of this enzyme and collect quality crystallographic data, we still had trouble solving the structure due to the atypical internal arrangement of the crystal and the lower resolution of the obtained crystallographic data.”

She signed up for the workshop with work that still needed to be completed, and with the help of lecturers, she finally succeeded. It was a truly international collaboration, on the result contributed for example, professor Kay Diederichs from the University of Konstanz or professor Randy J. Read and Dr. Tristan Croll from the University of Cambridge. Important data were obtained in CEITEC laboratories and measurements were also performed on a Swiss Light Source synchotron device in Switzerland.

“This is a perfect example of an integrated approach in structural biology, which combines several experimental approaches at the same time so that it is possible to solve the structure of biomolecules when one technique is not enough. The original, say, wild-type protein formed various types of oligomers and we failed to crystallize for a long time. Using protein engineering methods, we prepared a stabilized form of the enzyme that did not produce so many different types of oligomers, and we were able to crystallize it. Despite all the difficulties, the workshop managed to solve the crystal structure of this unexplored enzyme, which will help us understand the biological function of these very interesting biocatalysts, “described Schenkmayerová.
A manuscript of the publication is currently being prepared, we will inform you as soon as it is ready.

Fig. 1: Ing. Andrea Schenkmayerová PhD. with her leader RNDr. Ing. Martin Marek Ph.D.
Fig. 2: Photo of protein crystal