PhD. Topics

PhD. program Biophysics

Faculty of Mathematics, Physics, and Informatics, Comenius University in Bratislava

• Cellular mechanisms of adverse cardiotoxic effects of selected antipsychotics
  Bunkové mechanizmy kardiotoxických účinkov vybraných antipsychotík
  Name of the supervisor: Mgr. Zuzana Ševčíková Tomášková, PhD.
  Anotation:
  The treatment of mental disorders, such as bipolar disorder, depression, or schizophrenia is often associated by a whole spectrum of cardiotoxic side effects that can limit effectiveness of the patient´s treatment. Elucidation of the origin of these adverse effects could lead to design of a potential compensatory therapy, ultimately aiding patients in leading normal lives. The topic is focused on the study of the mechanisms by which cardiotoxic effects occur during the treatment of these mental disorders. In our laboratory, we found that lithium, often used in therapy of bipolar disorder, causes a significant decrease in the reserve respiratory capacity of cells, but does not change their basal respiration. This condition puts the cardiac cells at a disadvantage, and their collapse may occur under higher workload. Mitochondria are involved in the cardiotoxic effects of clozapine or risperidone. The aim of the work is to examine the effect of selected drugs on the bioenergetics of the cardiomyoblast cell line and their subsequent comparison. The drugs will be selected based on the described similar effects among patients (clozapine, lamotrigine, quetiapine, olanzapine, etc.). Since cardiac rhythm disorders are among the frequent effects, in addition to bioenergetics, we will analyze the spontaneous calcium events (calcium sparks), which also occur under physiological conditions. The frequency of occurrence of calcium sparks is related to the bioenergetic state of the cell. In addition to the functional properties, the work will also focus on monitoring of the changes in the expression and/or activity of individual proteins involved in the respiratory chain, their occurrence will be tested proteomically after chronic application of the drug. From the literature several signal pathways are known that are affected by the drug, but at the functional level, the behavior of cardiac cells in the presence of antipsychotics is rarely described, in contrast to the effect on neuronal cells. Methods: work with cell cultures, confocal microscopy (detection of mitochondrial membrane potential and calcium events, monitoring the redox state of cells), measurement of oxygen consumption in cells with a Clark electrode, selected methods of molecular biology (Western blot, PCR), enzymatic reactions, work with tissues and isolation of primary cardiomyocytes.

• Identification of chloride channel from cardiac tissue mitochondria
  Identifikácia chloridového kanálu z mitochondrií srdcového tkaniva
  Name of the supervisor: Mgr. Zuzana Ševčíková Tomášková, PhD.
  Anotation:
  Chloride channels are involved in the regulation of mitochondrial membrane potential under both physiological and pathological conditions. During ischemia/reperfusion injury, the chloride channels contribute to the generation of post-ischemic arrhythmias. Chloride channels from cardiac mitochondria are well described at the electrophysiological level. It was confirmed that the so-called CLIC (chloride intracellular channel) proteins are located in the mitochondria of cardiac cells. Under certain conditions, these proteins can function as ion channels. Furthermore, a ligand of translocator protein, which is also localized in mitochondria, has the same antiarrhythmic effects as a chloride channel inhibitor. The aim of the work is to link this knowledge and find out whether the native chloride channels that we described in our laboratory are identical to any of the CLIC isoforms and whether these proteins are in close contact with the translocator protein, which would explain the observed antiarrhythmic effect. The obtained results should clarify the molecular identity of native chloride channels from cardiac mitochondria and also explain the regulation of the chloride channel by ligands of the translocator protein. Methods: confocal microscopy (FRET analysis, induction of oxidative stress by laser, analysis of mitochondrial networks), molecular electrophysiology (measurement of current through one ion channel), selected methods of molecular biology, work with tissues and cell cultures.

PhD. program Biophysics

Faculty of Mathematics, Physics, and Informatics, Comenius University in Bratislava

• Effect of prenatal stress on molecular mechanisms implicated in corticosteroid-monoamine interaction in the heart and brain
  Vplyv prenatálneho stresu na molekulárne mechanizmy interakcie signálnych dráh kortikosteroidov a monoamínov v srdci a mozgu
  Name of the supervisor: Mgr. Marta Gaburjáková, PhD.
  Anotation:
  Stress is defined as an organism’s response to external stressors. Living organisms are exposed to various stressors all through their life, when the first exposure happens even before the birth (e.g. prenatal stress). Stress is not necessarily harmful; controlled exposure to the certain stressors might be even beneficial (e.g. cognitive behavioral therapy). On the contrary, chronic stress predominantly impacts cardiovascular and neuronal systems, resulting in the onset of numerous pathologies that stand as major global contributors to disability and mortality. Stress-induced cardiovascular and neuropathologies frequently co-occur, leading to a worsened prognosis for both. Current knowledge indicates that the interplay between corticosteroid (stress hormones) and monoamine (neurotransmitters) signaling pathways is a crucial determinant in whether a particular stressor, administered to an organism of a specific sex, will have detrimental, neutral, or potentially beneficial effects. The objective of the PhD thesis will involve a comprehensive investigation of the molecular mechanisms that underlie the interaction between corticosteroids and monoamines in the heart and brain of adult rats of both sexes, following exposure to prenatal stress. The primary emphasis will be placed on exploring the correlation between this interaction and intracellular Ca2+ signaling, which translates diverse signals into specific cellular responses. The main experimental approach will involve electrophysiological methods in combination with several biochemical techniques.

PhD. program Biochemistry

Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava

• Quartz microbalance-based aptasensors for rapid and specific detection of potential biomarkers
  Aptasenzory na báze kremenných mikrováh na rýchlu a špecifickú detekciu potenciálnych biomarkerov
  Name of the supervisor: Ing. Alexandra Poturnayová, PhD.
  Anotation:
  The need for fast, reliable and timely detection tools leads to the development of highly sensitive devices capable of detecting potential markers associated with various diseases. Such devices can also be biosensors, which in recent years have become a promising alternative to more common detection methods and can thus potentially change the way cancer is diagnosed and/or treated. The dissertation will be focused on the development of biosensors based on DNA aptamers for the detection of potential biomarkers of oncological diseases. The mass method - quartz microbalances - will be used for the development of biosensors.

• Interactions between maternal and embryonal neurotrophic factors: implication for neurodevelopment
  Interakcie medzi neurotrofickými faktormi matky a embrya: implikácia pre neuronálny vývoj
  Name of the supervisor: MMedSc Eliyahu Dremencov, DrSc
  Anotation:
  Brain derived neurotrophic factor (BDNF) is one of the key neurotrophic factors regulating neurogenesis and neuroplasticity. Aside from its primary role in the central neural system (CNS), BDNF also mediate certain functions of the female reproductive system, such as oocyte maturation and embryo development. Decreased levels of maternal BDNF during the pregnancy is associated with the embryo developmental abnormalities, including the CNS-related ones. It can by hypothesized that maternal BDNF induce the expression of the embryonal neurotrophic factors, via a mechanism involving BDNF-TrkB-VGF-TLQP62 pathway, and thereby modulates the development of the offspring CNS. This project will aim to test thus hypothesis, using neurochemical, neurophysiological, and behavioral neuroscience methods.

• DNA methylation changes accompanying the development of multidrug resistance
  Zmeny metylácie DNA sprevádzajúce rozvoj viacliekovej rezistencie
  Name of the supervisor: Mgr. Lucia Pavlíková, PhD.
  Anotation:
  The development of multidrug resistance (MDR), mediated by overexpression of ABC transporters, represents a difficult obstacle to overcome in cancer chemotherapy. The MDR phenotype is also accompanied by activation of other defense mechanisms that protect the cell from damage by cytostatic agents, even those that are not ABC transporter substrates. The origin of these mechanisms may be twofold. They may be directly related to the presence of ABC transporter in cells because of common mechanisms controlling their induction or they may have developed as a result of selection pressure of cystostatic drugs during treatment but independently of the induction of ABC transporter expression. It is changes in the methylation of promoter regions of genes whose modulation may be involved in the development of multidrug resistance that may be responsible for the wide variability in cellular responses to cytostatic-induced chemical stress and the frequently observed changes in the differentiation status of cells.

PhD. program Biochemistry

Faculty of Natural Sciences, Comenius University in Bratislava

• Sterol metabolism in yeast Saccharomyces cerevisiae under stress conditions
  Metabolizmus sterolov v stresových podmienkach u kvasinky S. cerevisiae
  Name of the supervisor: Mgr. Martin Valachovič, PhD.
  Anotation:
  Sterols are essential membrane lipids that organisms either synthesize or utilize from the environment. Different organisms prefer specific sterol molecules, thus it is requisite to discriminate between the structures so that incompatible sterols are excluded from membranes. Using the model organism S. cerevisiae, we are looking for mechanisms monitoring the quality of sterols in cells.

• Squalene production in non-conventional yeasts by metabolic engineering methods
  Produkcia skvalénu v netradičných kvasinkách metódami metabolického inžinierstva
  Name of the supervisor: Mgr. Roman Holič, PhD.
  Anotation:
  Squalene, a natural intermediate in sterol biosynthetic pathway, is widely used in several areas of human health, such as medicine, food, pharmacy and cosmetics. The aim of this work is to identify suitable species of non-conventional yeasts that would be able to accumulate squalene using traditional as well as modern genetic methods. The acquired knowledge can contribute to the biotechnological production of squalene by microorganisms and to the elucidation of the bioactive effects of squalene on human health.

• Study of the communication between mitochondria and the plasma membrane
  Štúdium komunikácie medzi mitochondriami a plazmatickou membránou
  Name of the supervisor: Mgr. Mária Balážová, PhD.
  Anotation:
  In the complex environment of cellular processes, communication is the cornerstone that governs essential functions, adaptation and survival. The importance of elucidating the communication between mitochondria and the plasma membrane lies in its key role in the adaptation of cells to environmental changes. Understanding how these two vital cellular components interact and synchronize their functions is critical to understanding cellular responses to stimuli.

• Role of lipid transfer proteins in the physiology of a eukaryotic cell
  Úloha proteínov prenášajúcich lipidy vo fyziológii eukaryotickej bunky
  Name of the supervisor: RNDr. Peter Griač, DrSc.
  Anotation:
  We will characterize selected lipid transfer proteins (LTPs). We will study the role of these LTPs in yeasts, selected human parasites, and alternatively also in higher eukaryotes. Use of LTPs as targets of antifungal or antiparasitic therapies will be analyzed.

PhD. program Animal physiology

Faculty of Natural Sciences, Comenius University in Bratislava

• Behavioural and neurobiological indicators of positive poultry welfare
  Behaviorálne a neurobiologické indikátory pozitívneho welfaru hydiny
  Name of the supervisor: RNDr. Ľubor Košťál, CSc.
  Anotation:
  The traditional approach to the study of welfare has focused primarily on the prevention of suffering, fear and pain. As a result, the science of animal welfare is heavily 'biased' towards the study of negative experiences. However, advances in science are leading us to consider positive animal experiences, also referred to as positive welfare. It is currently unclear what techniques, tests and procedures are appropriate for assessing positive experiences of farm animals, including poultry. The aim of this thesis will be to identify existing procedures for assessing positive welfare in poultry, to propose and test appropriate methods for assessing positive welfar in poultry, or to test ways to induce positive affective states.

• Characterization of proteins of the mammalian reproductive system, including gametes, in processes associated with fertilization
  Charakterizácia proteínov pohlavného systému cicavcov, vrátane gamét, v procesoch asociovaných s oplodnením
  Name of the supervisor: Ing. Jana Jankovičová, PhD.
  Anotation:
  In mammals, the successful fusion of gametes is a prerequisite for the formation of an embryo and a new individual. These events are preceded by a series of processes including the development, morphological and functional maturation of gametes in the environment of the male, or the female reproductive system and subsequently their mutual interaction in the fertilization process. Although these processes show certain common features in mammals, some mechanisms, as well as the expression of proteins at the gamete and tissue level, are different in individual animal species. The dissertation will aim to study the proteins involved in the maturation of gametes, or fertilization using cattle as a model organism, by immunohistochemical and biochemical methods, or molecular biology methods.

PhD. program Fyziológia živočíchov

Faculty of Natural Sciences, Comenius University in Bratislava

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  Rastlinné metabolity v liečbe mikrobiálnych infekcií testované na CAM modeli prepelice japonskej
  Name of the supervisor: Mgr. Mariana Máčajová, PhD.

PhD. program Animal physiology

Faculty of Natural Sciences, Comenius University in Bratislava

• Reciprocal interactions between monoamines and neurotrophic factors in a healthy brain and in CNS disorders
  Recipročné interakcie medzi monoamínmi a neurotrofickými faktormi v zdravom mozgu a pri poruchách CNS
  Name of the supervisor: MMedSc Eliyahu Dremencov, DrSc
  Anotation:
  Monoamines, such as serotonin (5-HT), noradrenaline, and dopamine, are brain neurotransmitters playing a key role in cognition and emotions. Monoamines closely interact with neurotrophic factors, e.g., proteins responsible for neuroplasticity, such as the brain derived neurotrophic factor (BDNF). It is well established that monoamines induce the expression of neurotrophic factors. The reciprocal relation, e.g., modulation of the excitability of monoamine-secreting neurons by neurotrophic factors, had received lesser attention. This project will aim to test the hypothesis that neurotrophic factors reinforce their own expression via a mechanism involving excitability of monoamine neurons. Multidisciplinary methodological approach, combining electrophysiological, behavioral, and neurochemical techniques, will be employed.

PhD. program Genetics

Faculty of Natural Sciences, Comenius University in Bratislava

• Functional characterization of new proteins required for meiotic chromosome segregation
  Funkčná charakterizácia nových proteínov potrebných na segregáciu chromozómov
  Name of the supervisor: Mgr. Martin Valachovič, PhD.
  Anotation:
  Meiosis produces haploid gametes from diploid precursor cells. This chromosome number reduction is achieved by a single round of DNA replication followed by two successive rounds of chromosome segregation. Our laboratory has previously identified several new proteins required for meiotic chromosome segregation. A PhD project will aim to reveal the function of these novel proteins and analyze their interaction with other factors involved in meiotic and mitotic chromosome segregation.

• Characterization of the new molecular mechanisms underlying the repression of gene expression in yeast
  Objasnenie nových molekulárnych dráh zodpovedných za potlačenie expresie génov v kvasinkách
  Name of the supervisor: Mgr. Martin Valachovič, PhD.
  Anotation:
  Eukaryotic cells have evolved two mechanistically distinct pathways to repair DSBs during mitosis: non-homologous end joining (NHEJ) and homologous recombination (HR). Our latest research revealed that the mutants carrying deletions of genes involved in the HR pathway exhibited more than 500 significantly upregulated genes, enriched for transcripts from subtelomeric genes, LTR retrotransposons, and antisense transcripts. The aim of a PhD project will be to reveal the mechanisms underlying this new phenomenon.

• Protective function of lipid particles in connection to sterol lipotoxicity
  Ochranná funkcia lipidových partikúl pri toxicite sterolov
  Name of the supervisor: Mgr. Martin Valachovič, PhD.
  Anotation:
  In addition to their storage function, lipid droplets have the potential to protect the cell from toxic sterols that may be taken up from the environment or accumulate in cells in the event of impaired sterol biosynthesis. Using the yeast Saccharomyces cerevisiae, we are looking for a mechanism(s) by which cells monitor structural differences in sterol molecules and transport harmfull sterols from membranes to lipid droplets.

• Squalene production in non-conventional yeasts by metabolic engineering methods
  Produkcia skvalénu v netradičných kvasinkách metódami metabolického inžinierstva
  Name of the supervisor: Mgr. Roman Holič, PhD.
  Anotation:
  Squalene, a natural intermediate in sterol biosynthetic pathway, is widely used in several areas of human health, such as medicine, food, pharmacy and cosmetics. The aim of this work is to identify suitable species of non-conventional yeasts that would be able to accumulate squalene using traditional as well as modern genetic methods. The acquired knowledge can contribute to the biotechnological production of squalene by microorganisms and to the elucidation of the bioactive effects of squalene on human health.

• Study of the communication between mitochondria and the plasma membrane
  Štúdium komunikácie medzi mitochondriami a plazmatickou membránou
  Name of the supervisor: Mgr. Mária Balážová, PhD.
  Anotation:
  In the complex environment of cellular processes, communication is the cornerstone that governs essential functions, adaptation and survival. The importance of elucidating the communication between mitochondria and the plasma membrane lies in its key role in the adaptation of cells to environmental changes. Understanding how these two vital cellular components interact and synchronize their functions is critical to understanding cellular responses to stimuli.

PhD. program Genetika

Faculty of Natural Sciences, Comenius University in Bratislava

• Role of lipid transfer proteins in the physiology of a eukaryotic cell
  Úloha proteínov prenášajúcich lipidy vo fyziológii eukaryotickej bunky
  Name of the supervisor: RNDr. Peter Griač, DrSc.
  Anotation:
  We will characterize selected lipid transfer proteins (LTPs). We will study the role of these LTPs in yeasts, selected human parasites, and alternatively also in higher eukaryotes. Use of LTPs as targets of antifungal or antiparasitic therapies will be analyzed.

PhD. program Microbiology

University of Veterinary Medicine and Pharmacy in Košice

• Characterization of bacterial microbiota of the skin in horses
  Charakterizácia bakteriálnej mikrobioty kože u koní
  Name of the supervisor: MVDr. Viola Strompfová, DrSc.
  Anotation:
  The skin, the largest and most exposed organ by surface area, represents an ecological niche for an enormous spectrum of microorganisms that contribute to the barrier function of the skin and skin homeostasis. Any changes in the population of commensal microorganisms are associated with physiological changes occuring during various dermatological diseases or aging. Nevertheless, the amount of knowledge on the composition, diversity and functions of the skin microbiota in horses is negligible. Knowing the taxonomic composition of the microbiota under physiological and pathological conditions and its properties will help with the search for appropriate therapeutic strategies in relatively frequently occurring dermatological diseases in horses, will help to improve welfare by accelerating healing, and will help to reduce the danger of antibiotic-resistant bacterial strains. Part of the work will be the search for suitable strategies for optimizing/stabilizing the bacterial population of the skin in order to preserve the physiological functions of the skin.

• Progressive eco-friendly and sustainable approaches to eradication of bacterial biofilms
  Progresívne ekologické a udržateľné prístupy k eradikácii bakteriálnych biofilmov
  Name of the supervisor: RNDr. Dobroslava Bujňáková, PhD.
  Anotation:
  Bacterial biofilms are organized aggregates of microorganisms that attach to diverse living or non-living surfaces using an extracellular polymeric substance that protects them from the host immune system and conventional antibiotics. Biofilms cause long-term, recurrent infections that result in millions of deaths around the world every year. Since biofilms are commonly associated with increasing antibiotic resistance different than that of the planktonic bacteria due to its multicellular structure, the currently available antibiotics are inadequate to treat biofilm-associated infections which have led to an immense need to find newer treatment options. The dissertation will focused on the recent progressive eco-friendly, sustainable approaches to eradication of bacterial biofilms that have the potential for future advancement on this field.

PhD. program Veterinary morphology and physiology

University of Veterinary Medicine and Pharmacy in Košice

• Use of non-traditional feed additives in organic sheep farming
  Využitie netradičných kŕmnych aditív pri ekologickom chove oviec
  Name of the supervisor: MVDr. Zora Váradyová, PhD
  Anotation:
  The topic is devoted to non-traditional polyphenol-rich agro-industrial by-products used as feed additives that can reduce the environmental burden of greenhouse gas (GHG) emissions in endoparasite-burdened sheep. The goal will be to determine the effect of pasture with a rich species diversity of plants and non-traditional feed additives in the form of agro-industrial by-products with a bioactive effect on rumen microbial fermentation, methanogenesis, lipid metabolism, and immunological parameters. Solving the topic will lead to obtaining new information about the potential use of non-traditional feed additives in a circular economy with lower dependence on chemical inputs and better use of locally available sources of polyphenols in the context of an agroecological approach.

PhD. program Zoology and animal physiology

Pavol Jozef Šafárik University in Košice

• Beneficial effect of polyunsaturated fatty acids on preimplantation embryo development
  Benefičný vplyv polynenasýtených mastných kyselín na preimplantačný vývin embryí
  Name of the supervisor: MVDr. Dušan Fabian, DrSc.
  Anotation:
  Large numbers of people are affected by infertility in their lifetime, according to a new report published by WHO. Around 17.5% of the adult population – roughly 1 in 6 worldwide – experience infertility. Furthermore, in recent decades, many studies have reported a worrisome decrease in the reproductive performance of farm animals. Embryo losses in the early stages of development represent a difficult problem for farmers, as the fundamental element of meat and dairy production is the successful reproduction of animals. However, by managing nutrition during the periconceptional period the incidence of losses can be decreased considerably. Dietary lipid supplementation can be a good strategy to reduce the extent of reproductive failure. Research has shown that polyunsaturated fatty acids (PUFAs) are extremely important and almost essential during pregnancy, especially in the last trimester. These acids are crucial for the proper development of the fetus's brain and eyes. Some of them not only pass through the placenta into the body of the growing fetus, but after birth continue into the body of the newborn through breast milk. Their presence is essential for the further development of the individual. The main aim of the study will be to evaluate the effect of diet supplementation with PUFAs, on the ability to conceive and to reduce early embryo loss in animal model - mouse females. The complementary set of relevant and up-to-date physiological, morphological, biochemical and molecular biology methods will be used in our experiments. Furthemore, acquired knowledge would result in targeted use in livestock production, veterinary practice as well as human reproductive medicine.