My message to the students? The main thing: Not to be afraid!
Mgr. Sandra Thalerová is a fresh holder of the prestigious prize Brno Ph.D. Talent, awarded by the South Moravian Center for International Mobility, for a project entitled “Models on a Chip for Determining the Mechanisms by Limitation of by Alteplasa Induced Thrombolysis”. Currently she works at the Institute of Biophysics of the Czech Academy of Sciences under the guidance of her supervisor Mgr. Jan Víteček, Ph.D. and at the same time she participates in the activities of the Stroke Research Team led by prof. MUDr. Robert Mikulík, Ph.D., as her part-time work at the International Clinical Research Center of St. Anne’s University Hospital. (FNUSA-ICRC). We have met both of them and asked for a short interview.
First congratulation on the award. Let’s start from the very beginning – how did you get to the research?
I came to my scientific activities during the bachelor’s study at Masaryk University in Brno. When choosing themes my choice was thrombolysis, which I was interested in due working with blood. I have always been interested in studying the physiology of blood, and the project also offered an outreach to clinical stroke research. I have devoted my whole bachelor study to this issue, and I continued on this work also at my master’s degree, under the leadership of Dr. Andrea Vítečková Wünschová, I have worked out my bachelor and master thesis on this topic and now I continue in my doctoral studies under guidance of Dr. Jan Víteček. And I hope I will continue further in research of stroke therapy.
How would you introduce your project to the general public, is it unique in something?
Sandra Thalerová: In our research, we focus on investigating processes during enzymatic thrombolysis, that is, dissolution a blood clot, thrombus, using a medicine called alteplasa. For this purposes we use in vitro models. We try to imitate as much as possible the vasculature (capillary bed) in the patients´brain. Such an experimental model allows us to monitor the efficiency of thrombolytic medicine, that is, the dissolution a blood clot in a real time. Furthermore, we use various miniaturizations, so-called “on-chip laboratories”, with their help we study interactions of medicine with thrombs. The uniqueness of these tools consist in fact that we are able to look at what often cannot be monitored in a patient. In short, it is very complicated to observe thrombolysis by a patient in a real time, whereas by using our models it is possible.
Jan Víteček: As mentioned, these are models, specifically silicone chips. However, the unique element is, that we use human blood and thrombs prepared from it. This has one huge and essential advantage: experiments are close to human physiological conditions. For example, animal models – rat, mouse or rabbit – are not quite ideal in the case of thrombolysis by reason of large interspecies differences in the structure and efficiency of thrombolytic enzymes, differences in vascular dimensions or blood flow in the brain. That is why we have taken these models to reflect human physiology as well as can be, though only on a chip in the in vitro system.
Brno Ph.D. Talent Award is definitely a great motivation for you. What direction do you want to move your research?
Sandra Thalerová: That is a difficult question…. I would like to optimize the models I work with, so that their parameters correspond as much as possible to human physiology. There are many options, such as lining the inside of artificial vessels with human cells and other improvements. I would like to build on what we already have and develop it further. It is a really unique project, not only in the Czech Republic.
Jan Víteček: The main goal of this project is improving the therapy. The currently used thrombolytic alteplasa has limited efficiency still, many patients do not respond to this therapy and it is not known why. So this is our visionary goal – to see where has this thrombolytic its deficiencies at the biophysical or biochemical level, and based on this data, thrombolytics can be designed to be more efficient and effective.
Sandra Thalerová: I would like to add, that enzymatic thrombolysis has a great future by stroke. As with myocardial infarction, ischemic stroke can be treated with a catheter. But that is much more difficult. However, the application of enzymatic thrombolysis is basically very simple – the patient is given a thrombolytic within one hour by infusion into a vein, and therefore, this procedure can be implemented anywhere in the world, even in developing countries. On the other hand, the mechanical thrombectomy can be used more or less only in technologically advanced areas. As long as, if the efficiency of enzymatic thrombolysis would be improved more or less in any way, then this could be a huge step forward in stroke therapy.
How difficult is your research? After all, the problem is that every blood clot is different…
Sandra Thalerová: Yes, thrombs are very different in their composition and structure both within individual patients and within the thrombs themselves. There is really a great variability, so we work with different thrombs´types, so we could contain their complex range as well as can be. We prepare them ourselves, the gateway is the blood collection from healthy donors, and from it are already prepared different types of thrombs, blood plasma, in short, all the material for our experiments.
Jan Víteček: Yes, this is a complicated research, but by using models we can relatively easily answer the questions that cannot be answered based on clinical data. In the clinic you actually have a clinical outcome of the patient, by using imaging methods can be found that after some time the vessel has loosened up, but how quickly the thromb degrades, I mean by biochemical markers, is not possible to detect at the patient yet. While we can look at these details using our models, we can also register the processes that cannot be detected in patients. When I return to that uniqueness, as far as I know, we are the only ones in the Czech Republic. There are other teams in the world working on similar research, we are talking about tens, but our advantage, which puts us to a certain foreground, is that we primarily work with human material and we try to reflect the real geometry of the vascular system in an appropriate way and use flow models. The classical access to thrombs studies is “in a test tube”, then under static conditions. While these systems allow monitor, for example, the amount of loosened red blood cells or the degradation products of fibrin from the thrombs, they miss its essential and it is the flow. The flow has, of course, an essential influence on the thrombolysis process. The pressure gradient mechanically deforms the blood clot and helps the thrombolytic to penetrate into the thromb. This is the essential advantage of our models.
Sandra Thalerová: At the same time, we are also able to measure the process of volume degradation or shrinking of thrombs in a real time. At certain time intervals, the thrombs in the thrombolysis process are scanned, and then, the size of the tromb in time is evaluated by using the image analysis. For example, we obtain information about the time phase of the hourly thrombolytic process that leads to the most rapid thromb loss. That would be in patients very complicated, of course.
You are working at Institute of Biophysics of the Czech Academy of Sciences and also at FNUSA-ICRC, how does it work together?
Sandra Thalerová: Thanks to the Stroke Research Program led by Professor Robert Mikulík in Brno, there is a close cooperation between the particular workplaces and the joint research is going one way – to improve the therapy of stroke. Both the Institute of Biophysics and the FNUSA-ICRC are members of this initiative, so there is no problem with coordinating the activities.
Jan Víteček: I have it similarly, I work primarily at the Institute of Biophysics and at the same time I am a member of the research team of FNUSA-ICRC – Inflammatory diseases – led by Doc. Lukáš Kubala, Ph.D. Except our institutions, there are several Brno institutions involved in this initiative, primarily FNUSA, our team on behalf of the Institute of Biophysics of the Czech Academy of Sciences, Loschmidt Laboratories of the Masaryk University, Veterinary Research Institute, BioVendor company, University Of Veterinary and Pharmaceutical Sciences Brno and Institute of Scientific Instruments of the Czech Academy of Science. Each of these institutions provides its expertise for solution of the common goal, which is the stroke therapy research. FNUSA provides clinical documents and where to point the research with regard to the patients. We are able to practise biophysical measurements in in vitro models and correlate these results with clinical ones. Professor´s Damborský team (Loschmidt Laboratories) has a world-class expertise in protein engineering. In short, a group of people gathered, each working on its puzzle piece, which, if put together, there is a great expectation to progress in the stroke therapy.
Is there anything you would like to say to students, researchers in the beginning?
Sandra Thalerová: Certainly not to be afraid of the research – I say that to my colleagues, students who are very clever. Let them follow what they are interested in, let them attend conferences or competitions, where they can learn something new and meet interesting people… No one has to be worried about working in the lab. So, not to be afraid, not be ashamed and just try everything.