A typical day starts with going over the experimental planning of the day, and then starting the experiments or data analysis, studying, or writing scientific papers. There is some flexibility and some level of control over your day. However, all experiments are very time-consuming and require a constant level of attention to detail, keeping track of your timings, and great planning. Almost every task is time-consuming, from planning the experiments, to doing them, redoing them, analyzing the data, and so on. It is common to be doing more than one experiment at a time and so sometimes the juggling can go wrong.

My research is focused on studying the molecular mechanisms in the invasion process of breast and lung cancer. In research, we each focus on a very narrow subject, on a specific group or even just a single protein, and try to determine the impact it has on different cellular processes. This helps us find new diagnostic tools, new treatments and potentially even cures.

I, personally, work with different techniques, so there is no specific routine, which is something I enjoy. But for instances, a day could be, starting in the morning with taking care of orders necessary for my research and replying to emails. Then I would go to a laminar flow hood to work with my cell cultures, either to maintain them or to perform experiments on them. After the experiment is done, I could extract protein from my cells, then do protein quantification and prepare the samples to run on what we call gel electrophoresis or Western Blot.

After this experiment is done, I would block and incubate the resulting membranes to evaluate the next day. Other times the experiment could be to fixate my cells and incubate with specific antibodies to visualize using a confocal microscope. Or I could be cloning my cells with specific genes and then tracking their effect using live imaging or some biochemical assay. Other times I will be receiving training in either some specific equipment or technique or in overall topics specific to my fields through webinars and conferences.

Working overtime is also very common and when working with living disease models (cell cultures, mouse models) working the weekends is also normal.

It’s also busy, hard work, and a lot of stress due to the constant stream of deadlines but also rewarding and exciting when you finally get some nice results and definitely always a nice challenge. The great part of doing research is to satisfy curiosity and the challenge of figuring out how to get the answers you seek.

MCSS team

Sofia Morazzo (in the middle) and Molecular Control of Cell Signaling Research Team.

Manlio Vinciguerra, Ph.D., MSc, the head of the Epigenetics, Metabolism and Aging research team at International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC), collaborated with colleagues from other institutions to publish a study on the use of senolytic drugs dasatinib and quercetin (D+Q) in targeting obesity and age-dependent nonalcoholic fatty liver disease (NAFLD) in mice xenografted with human hepatocellular carcinoma (HCC) cells.

NAFLD affects more than 25% of the population and is the most common chronic liver disease. It poses a challenge in both prevention and treatment and can lead to the development of fibrosis, cirrhosis, and even HCC, which is the main cause of cancer-related deaths.

The study used senolytic drugs, which target and eliminate senescent cells. Senescent cells are those that have permanently stopped dividing but did not die. While senescence is essential for many functions such as homeostasis or limiting tumor growth, many studies have already shown that when senescent cells accumulate, they can become harmful to other healthy tissues. “In the context of liver disease progression, the concept of selective elimination of senescent cells using senolytics holds a great therapeutic potential,” states Vinciguerra, as the use of senolytics presents a promising way to treat not only NAFLD but also many other age-related diseases.

The results have shown that the specific combination of (D+Q) used to treat NAFLD in mice has unexpectedly led to a mild increase in the severity of the disease, and the study thus concluded that the combination of senolytics used was ineffective in the treatment of NAFLD-caused HCC. “While elimination of some senescent cells is beneficial for healthy aging and overall lifespan, it is very important to identify which senescent cells are targeted by specific senolytics and their overall effects on health span,” explained Vinciguerra.

You can find the study here: 

Manlio-Vinciguerra

On Friday, June 25, Giancarlo Forte was bestowed upon the title of Cavaliere dell’Ordine della Stella d’Italia (Knight of the Order of the Star of Italy) from the Ambassador of Italy, H.E. Mr. Francesco Saverio Nisio. This award – the second highest civilian commendation in Italy – is given as a special recognition of merit in promoting friendly relations, promoting Italian prestige abroad and cooperating with other countries.

Giancarlo Forte works at the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC) for the eighth year. He came to the Czech Republic from Japan, where he worked in one of the largest research centers, the National Institute for Materials Science. In FNUSA-ICRC, he built the Center for Translational Medicine, which operates in the premises of Biology Park Brno.

He is the principal investigator of the research team Mechanobiology of Disease. In his work he deals with the properties of stem cells, which have the potential to replace and regenerate damaged tissues, and can be used in the treatment of serious cardiovascular, metabolic, neurological and oncological diseases.

During the coronavirus pandemic, he and his team actively participated in research related to COVID-19. Part of his team helped set up and participated in the testing activities of the covid lab. Moreover, thanks to contacts in his native Italy, Brno scientists helped test nanotray filters and determined their permeability for certification purposes, as Italian laboratories were overwhelmed by testing and evaluating samples.

During the ceremony, held at the Institute of Italian Culture in Prague, Dr. Forte and his group gave as special present to the Ambassador: they printed a high quality microscopy picture of human stem cells, which rwe elaborated as to recall the colors of the Italian flag. The gift was highly appreciated by the Ambassador.

Congratulations to Giancarlo Forte and we wish many more successes!

Forte_Award

Forte_Award_Gift

How to improve health not only in excluded localities is solved by the project Saste Roma (Healthy Roma), which started in the International Clinical Research Center of St. Anne’s University Hospital Brno. The three-year project aims to increase health literacy about the most serious diseases and a number of experts across the Czech Republic are involved in its solution.

The average life expectancy for Romani men is 57 and for Romani women 65 years. This is approximately 18 years less compared to the majority population. Compared to the majority of the population, Roma also suffer twice as often from multiple diagnoses (more than one serious disease). It is often due to ignorance of how to take care of their health, lack of information and support for lifestyle changes or shyness from visiting a doctor. This should be changed by the Saste Roma project aimed at the prevention of serious diseases in excluded localities, the most frequent inhabitants of which are the Roma.

The result of the almost three-year project will be a number of educational tools, from information brochures, through cultural events, educational e-learning, to a mobile application. “The project will focus on the development, implementation and evaluation of a multi-year health campaign in excluded localities. We will cover the most serious diseases, whether cerebrovascular, cardiovascular, oncological or mental illnesses, “explained Hana Maršálková, head of the Saste Roma project and head of the Public Health group within the Cerebrovascular research program that implements the project. “Online tools, applications and awareness-raising events will also be available and usable for the general public, and we also dedicate a special part to schoolchildren,” added Maršálková.

An expert team is working on the outputs, which now includes about 40 experts from the ranks of doctors, sociologists, educators, health marketing specialists and experts on excluded localities. A number of institutions also took part in the project – several clinics of the St. Anne’s University Hospital Brno, the University Hospital Brno or the Masaryk Memorial Cancer Institute. An important factor of success will also be the involvement of field workers from the State Health Institute, the Regional Hygiene Station or organizations supporting Roma communities.

“Every project focused on the health of the population in socially excluded localities is very much needed and the positive effects on the health of the population are also reflected in the overall improvement of the social situation,” confirms the importance of the project MUDr. Marie Nejedlá, Head of the Public Health Support Center of the State Institute of Public Health. Dr. Nejedlá and her team of field workers will ensure the dissemination of the project’s educational tools directly in the target communities.

“The project will be complemented by a questionnaire survey in the target areas, which map the knowledge and attitudes of the population and also verify how effective the health intervention was. Thanks to the scientific approach, we want to ensure that the project and its follow-up activities will be as effective as possible, “concludes Professor Robert Mikulík, expert guarantor of the project from the St. Anne’s University Hospital Brno and guarantor of the cerebrovascular diseases section.

 

The Saste Roma project – Developing health in excluded localities is financed from the EEA Funds 2014-2021, project no. ZD-ZDOVA2-002.

The involvement of the SZÚ takes place within the project Effective support of the health of persons at risk of poverty and social exclusion OPZ ESF, reg. No. CZ.03.2.63 / 0.0 / 0.0 / 15_039 / 0009439.

Press_Conference_Saste_Roma

The prize of the Dean of the Faculty of Science of Masaryk University was awarded to two researchers from the Protein Engineering team of the International Clinical Research Center of St. Anne’s University Hospital Brno. In the category of the Best Student of the Doctoral Study Program, Ondřej Vávra and Jan Štourač received it, as an evaluation and thanks for their work so far in the Loschmidt Laboratories of the Faculty of Science, Masaryk University and FNUSA-ICRC. On this occasion, we asked both colleagues who specializes in bioinformatics for a short interview.

I imagine bioinformatics as such IT guys in the laboratory. Is it true? And what have you already programmed in?
Ondřej: I probably wouldn’t describe it that way, it’s about a combination of IT and biology, but we are not programmers in laboratories například For example, I consider myself a self taught IT guy. I started at the high school, with Pascal. Then I worked in Bash, but in Loschmidt’s labs I needed more complex scripts to process the data, so now I’m working in Python, where I’m still a slightly advanced user and I’m happy to be sitting in the office with Jan, who can help me.
Jan: In my case, it’s more IT than biology or work in laboratories… I started programming in elementary school, my first programming “language” was Baltík and his simple programming of the wizard by graphical chaining of actions. At the gym I was a classic webmaker, so HTML, cascading styles, JavaScript, then PHP, SQL and in high school in the Pascal seminar. Currently, it’s mainly Java for more complex applications and Python as a fast prototyping language.

So how did you get into Loschmidt’s labs?
Ondřej: My journey was quite steep, I come from Hradec Králové and I had no idea about any Loschmidt laboratories. I chose to study at university mainly because of biology, which always attracted me the most. I got to Masaryk University, majoring in molecular biology. In the first semester, we had a seminar with the heads of all laboratories, where they presented their research activities. There I learned about Loschmidt’s labs for the first time and I was very interested in the combination of IT and biology. And when I met structural biology in my sophomore year, it was decided. I have already done my bachelor’s thesis here and I am satisfied here.
Jan: It was easier for me and a little earlier. Im from Brno and we had to take part in Secondary School professional activities at our gym. And in the search for a suitable topic, I was fascinated by bioinformatics as a fascinating connection between computer science and biology, and that was only a step to Masaryk University and Loschmidt’s laboratories. I then continued working on the projects even after the completion of it and I have already stayed here.

What are your results during your time here and what are your next goals?
Ondřej: My probably biggest result is that I participated in the development of a method for rapid analysis of the passage of molecules through protein tunnels. We successfully performed several other analyzes with this method, thanks to an internship abroad, we established further cooperation, so we managed to evaluate it well. Three years ago, I also received the Brno Ph.D. The talent of the South Moravian Center for International Mobility (JCMM), however, I am now in the fourth year of doctoral studies, so it is most important for me to combine work here with writing a doctoral thesis. So the closest goal is to complete my project and finish it successfully.
Jan: I primarily deal with the design and development of bioinformatics tools and databases. And it can be said that in some way I have been involved in almost everyone who has come out of our lab in the last ten years, which is twelve or thirteen programs. What makes me most happy is that they are popular in the scientific community and are really used by thousands of scientists around the world. As for studying, I’m in my second year, so in a while I will have a state exam and then I’ll see. And if the pandemic situation allows, I would like to go on an internship at the European Bioinformatics Institute in Great Britain this year. But now it’s hard to plan anything, so it’s hard to say how it will all turn out in the end.

The most difficult you have encountered in your work so far, and what obstacle do you face now?
Ondřej: It was a purely professional problem, within the project in foreign cooperation I needed to integrate a special kind of simulations, which we have not done here yet. Long story short – it took about a year before I managed to find and put into operation a usable method and everything finally worked out. Now I face another obstacle. So far, there is no reliable automated method that can decide whether a protein has a ligand binding site on the surface or inside. If this problem could be solved and we could use software tools to determine the nature of these places, it would be a huge step forward. Using machine learning, we could apply this knowledge to the entire protein database and then better design changes to proteins or ligands, which would have an impact not only on applications in medicine, but also in industry.
Jan: I deal with one very difficult matter somehow continuously. It is about the robustness of our programs. Our calculations are quite demanding and run simultaneously on many computers. And as we all know, from time to time one stops randomly working or responding, and this then leads to a false calculation failure, which is a problem. So we’re working to keep the running task running as well as possible, and for example to restart automatically, without the user noticing anything and we have to apologize for the technical inconvenience. But this is more of a technical matter, from a scientific point of view, the biggest challenge for me at the moment is the development of the PredicSNP Onco tool. It is a software aimed at the personalized treatment of children’s cancer, which aims to analyze the effect of mutations found in the cancer tissue of a particular patient on the functioning of key proteins and their interaction with known drugs. The results obtained by us will then be used by physicians in deciding and preparing a suitable therapeutic plan.

What do bioinformatics say about the threats posed to us by filmmakers like Matrix or Terminator?
Ondřej: Probably nothing, we have fun like other viewers 🙂 I have no specific fear of any IT thing. I don’t have an Internet of Things facility at home, but it’s more of a question that I don’t care so much. And if I want to adjust the household to some automatic mode, then in the first place I will deal with security, which is something that a lot of people forget. As far as machine learning is concerned, it’s more of a question for Elon Musk or Bill Gates, where they are going to go, I’ve never thought about it. It will definitely affect our lives, for example, let’s take semi-autonomous cars, so we will see what it will look like in ten years.
Jan: Rather than the plots of the mentioned films, I am frightened by the “big brother” and the associated loss of privacy. Today, we almost always communicate to third parties, whether search engines, visited sites or social network operators, an awful lot of information that can be used to extract incredible details about our lives, habits and so on. And they can be easily abused, as in China in their social credit system, which seems very scary to me. And unfortunately it’s not sci-fi, but it’s here and now, and using it anywhere in the world is “just” a matter of justification. This is associated with the risk of theft of private data or identity by a completely stranger. Although I am glad that the state is gradually digitizing, I have no major illusions about information security. Globally, IT security is often perceived as an unnecessary and expensive luxury, and is basically not addressed until a problem arises. Unfortunately.

Let’s leave the IT topic – what about free time?
Ondřej: I recently found a new hobby – I make mechanical keyboards. Otherwise, music or reading to take a break from that computer.
Jan: For me, it’s definitely nature and trips. I like to walk in the mountains, in the woods and try to spend as much free time as possible outside the computer and the Internet. On weekends, I prefer to volunteer with the Brontosaurus to take care of valuable natural sites or monuments.

Stourac_Vavra

The CZECRIN research infrastructure invites all interested parties to its annual scientific conference 2021. The conference program is already out there and you can view it on the CZECRIN website. If you are interested in a topic, but you have already blocked the date, you can still register for the conference and get a record of the entire conference.

If you are already looking forward to the conference and would like to shorten the wait, CZECRIN has prepared a small competition quiz for you, in which you can test your knowledge of CZECRIN and clinical research and you can also participate in the prize draw by participating. Attention, if you want to participate in the draw, you must be registered for the conference. The evaluation of the quiz will take place at the end of the CZECRIN Conference.

The CZECRIN research infrastructure, which is part of the pan-European ECRIN-ERIC network, offers its support, services and expertise to all research-oriented physicians in order to join forces in a rapid approach to the initiation of national and especially transnational clinical trials.
St. Anne’s University Hospital Brno and International Clinical Research Center, together with Masaryk University, is a founding member and main coordinator of this Czech national infrastructure.

Thank you for your great interest, the study is already full.

Do you want to prevent the development of diabetes? Not satisfied with your weight? Are you not feeling well in your body? These three questions are part of the campaign for recruitment to a new project to support the right lifestyle, which will start during the holidays at the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC).

The pilot research project will be implemented by the Kardiovize research team, where scientists will focus on diseases associated with poor lifestyle. “We will first evaluate an individual’s current condition, such as physical activity, medical history, or eating habits, and use this information to determine the risk of developing type 2 diabetes,” said Juan Pablo Gonzalez Rivas, head of the research team. This will be followed by a consultation with a doctor, nutritionist and trainer in order to draw up a three-month individual plan. Its goal will be to motivate the patient to lose weight, and related improvements in glucose, lipids and blood pressure – in short, to improve his health and quality of life.

Anyone aged 25 to 75 years with a body mass index (BMI) between 25 kg / m2 and 40 kg / m2 can be included in the study. Determining the approximate BMI is simple, just a calculator. It is the ratio of weight and square root of height in meters. The pilot project will run for a total of six months, after a medical examination and examination by a nutritional therapist, the selected individuals will begin a lifestyle change program under the guidance of a specialized coach. Blood samples will also be taken during the study to measure blood fats and sugars.

“It is really a challenge for us, and if it succeeds on a local scale, we would like to expand this program for the entire Czech population. We want to help as many people as possible,” added Gonzalez Rivas.

DETAIL INFORMATION
Who we are looking for: people in the age 25–75 years, whose body mass index (BMI) value is in the range of 25 kg / m2 to 40 kg / m2 (BMI calculation: weight / square root of height in meters).

How will the project go? The project will last 6 months, during which time the selected candidates will undergo a medical examination and an examination by a nutrition therapist. After your first visit to the doctor, you should begin a lifestyle change program led by a lifestyle coach.
Meetings with the coach will take place weekly for three months and then every two weeks until the program is completed. In total it will be 16 sessions. Each session will last one hour at a time. You will receive discussion materials at each session. At home, you should record the amount of food and drink consumed, as well as the type of physical activity and its duration. Records should be kept throughout the project, ie 6 months.
During the study, blood samples will be taken to check your blood fats and sugars at baseline, after two months, and at the end of the study. If the test reveals high levels of blood pressure or blood fats, your doctor will recommend appropriate treatment in addition to lifestyle recommendations during the consultation.
Due to the current situation, which is affected by the COVID-19 pandemic, it is possible to interview the coach, both in person and online.

For whom the project is not suitable: if you suffer (or have suffered) from any of these diseases, participation in the program is unfortunately not possible for you: proven diabetes, cancer, ischemic heart disease, stroke, angina pectoris, peripheral vascular disease, heart failure or kidney disease, other serious kidney disease, osteoarthritis of the knee, ankle or hip joint, moderate to severe lung disease, or other disease that prevents moderate physical activity. Participating in the project is also not suitable for you if you are taking certain medications, such as chemotherapy, blood thinners and medicines that affect body weight (for example, orlistat, pregabalin, etc.). Another exclusion criterion is pregnancy or pregnancy planning during the project, or if you know in advance that you will not be able to attend most sessions of the program.

Project start: June 2021 (recruitment), July (start of intervention)

Please note that once the capacity is filled, recruitment to the project will be completed.

How to apply for the project?
You can apply by phone at 543 185 592, 603 299 683 (on working days, between 9.00 am and 3.00 pm) or via the email address infokardiovize@fnusa.cz.

Thank you for your great interest, the study is already full.
We will be happy to answer any questions. From all applicants, applicants meeting the project criteria will be selected and subsequently invited to participate.

We are looking forward to collaborate with you.

Prevent activation of the cellular receptor, which slows growth and causes achondroplasia. A groundbreaking method of treating genetic disorders of growth has been described by scientists from the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC) and Masaryk University in Brno, together with Japanese colleagues.

The key substance in this case is an RNA aptamer with the James Bond name RBM-007, which acts as a ligand trap. Ligands are usually small proteins that form complexes with cellular receptors and can activate them. In the case of achondroplasia, it is the FGFR3 receptor whose increased activity slows the growth of cartilage cells. An aptamer is an engineered portion of a ribonucleic or deoxyribonucleic acid that binds to a ligand that can no longer activate FGFR 3 receptors, thereby preventing growth disorders.

Pavel Krejčí, head of the FNUSA-ICRC Cell Signaling research team, contributed significantly to this discovery. “The Japanese company developed this RBM-007 for the treatment of AMD (Age-related Macular Degeneration), however, we noticed its potential for the treatment of growth disorders and started working in this area,” Krejčí described the beginnings of the cooperation. That was five years ago and now RBM-007 is entering the first phase of clinical trials and is being tested in Japanese patients. The results are very promising, however, testing a new drug is a long way off. “Drug for achondroplasia – Vosoritide, which I participated in the research, will reach the first patients after more than sixteen years,” Krejčí added.

The main focus of the FNUSA-ICRC Cell Signaling team, ie research into receptor tyrosine kinases, which currently includes FGFR3, is far from over. “Currently, we have about fifteen projects under development,” Krejčí confirmed. One is the study of aptamers that would not function as a ligand trap but inhibit receptors directly. The result could be a new generation of molecules with great potential for the treatment of diseases related to damage to various organs, not just bones. “We are trying to create a bridge between basic and clinical research. So far, we are doing well, hopefully it will last in the future, ” added Pavel Krejčí.

The publication was published in the prestigious journal Science Translational Medicine and can be found here:

Achondroplasia is a genetic form of dwarf growth, the height in adulthood in those affected by this disease is on average 125 cm. It is the most common form of genetic growth disorder in humans, and is caused by mutations in the FGFR3 gene. In the Czech Republic, 4-5 children with this disorder are born annually. Four years ago, scientists from the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC) founded register of these children, thanks to which they collect data on their health.

RNDr. Jan Fröhlich, Ph.D. and Dr. Manlio Vinciguerra of the Epigenetics, Metabolism and Aging FNUSA-ICRC Research team, in collaboration with a research institute at the Medical University in Varna, published a successful review summarizing current knowledge on the effect of adipomyokines / metabotrophic factors on the development and progression of cardiometabolic (CMD) and neurodegenerative diseases. The work was published in the International Journal of Molecular Sciences.

“Over the last 30 years, there has been a significant change in the view of adipose tissue, which is now understood as an important regulator of metabolism and one of the main endocrine organs of the human body,” says Dr. Jan Fröhlich with the fact that adiopobiology has thus become an important scientific field, dealing, among other things, with the study of the origin and consequences of obesity. It plays an important role in the pathophysiology of cardiometabolic and neurometabolic diseases, including Alzheimer’s disease (AD).

“According to the latest findings, one of the main risk factors for the onset and progression of Alzheimer’s disease is obesity and the associated hypertension, high LDL cholesterol and diabetes. On the contrary, numerous studies in mouse models and volunteers have shown that starvation-induced diets or short-term exercise have a beneficial effect and slow the development and progression of neurodegenerative diseases, including AD, ”explains Dr. Jan Fröhlich.

It has been shown that mediators of positive effects are factors / hormones secreted from skeletal muscle and adipose tissue, so-called adipomyokines. Adipomyokines are a heterogeneous group of metabolites and proteins that have a direct effect on metabolism and are therefore also nicknamed metabotrophic factors. “In our work, we point out that therapies based on the modulation of metabolism through the administration of metabotrophic factors could in the future help patients suffering from serious cardiometabolic and neurodegenerative diseases,” points out Dr. Jan Fröhlich.

The full article is available HERE.

The Hands-on Computational Enzyme Design Course is a highly practical and interactive course meant primarily for protein and metabolic engineers with no prior experience in computer modelling and bioinformatics. Other experts willing to broaden their current computational protein design toolbox can also benefit from this course. A team of experts and software developers provide training on how to operate several software tools devoted to different aspect of enzyme engineering, and how to properly interpret the results. Four main topics covered are: (i) Mining and analysis of novel enzymes, (ii) Engineering protein stability, (iii) Engineering enzyme activity and specificity, and (iv) Engineering protein solubility. The theoretical background and practical exercises are provided in a dynamic discussion environment.

The first edition of this course was carried out in the classical on-site format for 3.5 days, in Brno, Czech Republic, in February 2020. The course was organized by the Loschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University and International Clinical Research Center, St. Anne’s University Hospital Brno. Due to the COVID-19 pandemic, the second edition of the course was performed on-line in May 2021. Both editions were fully booked and the feedback from the participants was very positive. The great majority of the participants was highly satisfied and would recommend the course to a colleague. The 2nd edition was fully booked after only 2 weeks, with participants from 16 countries and 4 continents, 12% of them coming from industry. Our experience shows that: (i) by running an on-line edition we shortened distances, allowing participants from farther regions of the globe to join, (ii) the demand for training on computational enzyme design tools is high, and (iii) the reputation of the Loschmidt Laboratories as providers of valuable tools and training is growing.

We plan to run in the future both on-site and on-line versions of the course. If you are interested in participating in the next edition, you can access the course website and sign up to our newsletters to stay tuned!
Contact: Dr. Serqio Marques – smar96@gmail.com