PhD. Topics

PhD. program Biophysics

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

• The novel psychoactive cannabinoid hexahydrocannabinol (HHC): molecular and electrophysiological characterization of its effects in the nervous system
  Nový psychoaktívny kanabinoid hexahydrocannabinol (HHC): molekulárna a elektrofyziologická charakterizácia jeho účinkov v nervovom systéme
  Name of the supervisor: RNDr. Katarína Ondáčová, PhD.
  Anotation:
  Hexahydrocannabinol (HHC) is a novel semi-synthetic cannabinoid derived from naturally occurring cannabinoids. Its psychoactive effects have been observed following consumption, predominantly among young adults. Although HHC is known to bind to cannabinoid receptors, its downstream signaling pathways and its influence on neuronal excitability have not yet been systematically investigated. This study aims to elucidate the effects of HHC on cannabinoid receptors, neuronal firing properties under in vitro conditions, and its impact on brain function in vivo.

• Effect of acute or chronic stress on intracellular Ca2+ signaling pathway
  Vplyv akútnej a chronickej stresovej záťaže na vnútrobunkovú Ca2+ signálnu dráhu
  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 chronic exposure happens even before the birth (e.g. prenatal stress). 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. These findings suggest that during chronic stress, the same signaling pathways are affected in both the brain and the heart. In contrast to chronic stress, acute stress is an evolutionarily important adaptive response to threat, termed the ‘fight-or-flight’ response. However, in the presence of point mutations in the intracellular Ca²⁺ channel (ryanodine receptor), the acute stress response poses a significant risk for cardiac arrhythmias. The molecular mechanisms of this arrhythmogenic disorder, which is symptomatically manifested only during emotional stress or physical activity, are not well understood. The objective of the PhD thesis is to conduct a comprehensive investigation of the remodeling of intracellular Ca²⁺ signaling pathway, which translates diverse stimuli into specific cellular responses. Particular emphasis will be placed on the effects of prenatal stress on the interplay between glucocorticoid (stress hormone) and Ca²⁺ signaling pathways in the heart and brain of adult male and female rats (in vivo model of stress). Additionally, the effects of acute stress will be examined in an in vitro stress model at the level of single ryanodine receptors. The primary experimental approach will combine in vitro electrophysiological techniques with a range of complementary biochemical methods.

PhD. program Biochemistry

Faculty of Chemical and Food Technology of STU in Bratislava

• Biomarkers of Early Cancer Diagnosis: Development of Aptamer-Based Biosensors and Their Clinical Validation
  Biomarkery včasnej diagnostiky onkologických ochorení: vývoj aptamérových biosenzorov a ich klinická validácia
  Name of the supervisor: Ing. Alexandra Poturnayová, PhD.
  Anotation:
  Early diagnosis of oncological diseases represents one of the key factors in improving patient prognosis and survival. Despite intensive research efforts, reliable, highly sensitive, and non-invasive biomarkers suitable for routine clinical practice are still lacking. This PhD thesis focuses on the identification and experimental validation of potential biomarkers for early cancer diagnosis, particularly circulating microRNAs and exosomes, through the development of advanced aptamer-based biosensors. The main objective of the thesis is the design, optimization, and characterization of electrochemical and QCM biosensor platforms based on specific DNA aptamers, enabling highly selective and sensitive detection of target biomolecules in biological samples. The work will include a detailed analysis of aptamer–biomarker binding interactions, evaluation of key analytical parameters of the biosensors (limit of detection, linear dynamic range, selectivity, and reproducibility), and their systematic comparison with conventional diagnostic methods. The developed biosensors will be tested using clinically relevant blood samples in collaboration with clinical partners, ensuring clinical validation and assessment of their application potential. The results of this PhD thesis have the potential to contribute to the development of non-invasive diagnostic tools, support the implementation of liquid biopsy approaches in clinical practice, and expand the possibilities of personalized oncological diagnostics.

• Consequences of combined therapy of maternal depression on rat offspring
  Dôsledky kombinovanej terapie materskej depresie na potomstvo potkanov
  Name of the supervisor: prof. RNDr. Ľubica Lacinová, DrSc.
  Anotation:
  The work will focus on the consequences of drug-resistant depression and its treatment during pregnancy on the brain development of the offspring. For this type of depression, a combination of antidepressants is used. We will use the antidepressants aripiprazole (ARI) and ARI in combination with sertaline (SER). We will compare the functional brain development and neurobehavioral consequences in the offspring of rats of both sexes, while evaluating the impact of maternal depression alone and the impact of ARI and ARI+SER treatment. We will focus on the hippocampus and changes in its electrical excitability, in neurogenesis, biochemical, and structural changes.

• The novel psychoactive cannabinoid hexahydrocannabinol (HHC): molecular and electrophysiological characterization of its effects in the nervous system
  Nový psychoaktívny kanabinoid hexahydrocannabinol (HHC): molekulárna a elektrofyziologická charakterizácia jeho účinkov v nervovom systéme
  Name of the supervisor: RNDr. Katarína Ondáčová, PhD.
  Anotation:
  Hexahydrocannabinol (HHC) is a novel semi-synthetic cannabinoid derived from naturally occurring cannabinoids. Its psychoactive effects have been observed following consumption, predominantly among young adults. Although HHC is known to bind to cannabinoid receptors, its downstream signaling pathways and its influence on neuronal excitability have not yet been systematically investigated. This study aims to elucidate the effects of HHC on cannabinoid receptors, neuronal firing properties under in vitro conditions, and its impact on brain function in vivo.

• Polymeric nanoparticles carrying mRNA in the treatment of acute central nervous system injury and their biodegradation in the organism
  Polymérne nanočastice nesúce mRNA pri liečbe akútneho poškodenia centrálneho nervového systému a ich biodegradácia v organizme
  Name of the supervisor: RNDr. Katarína Ondáčová, PhD.
  Anotation:
  Nanomedicine currently represents a significant therapeutic potential in the treatment of a wide range of diseases. Acute injury of the central nervous system (CNS) constitutes a serious medical and socio-economic problem, particularly due to the limited regenerative capacity of the CNS. The aim of this study is to investigate whether polymeric nanoparticles carrying mRNA encoding a specific protein, or alternatively a therapeutic compound itself, are capable of influencing the regeneration of damaged CNS tissue and to elucidate the mechanisms underlying these effects. Furthermore, the analysis of the biodegradation of polymeric nanoparticles will contribute to a better understanding of their biodistribution and behavior within the organism.

• The relationship between transposons and gene control
  Vzťah medzi transpozónmi a génovou expresiou
  Name of the supervisor: Mgr. Jana Královičová, PhD.
  Anotation:
  Transposons account for a significant part of the human genome and play a role in regulating gene expression. Repetitive elements are found in pre-mRNA and can generate exons that acquire a new function within the transcript or cause genetic diseases. A large portion of transposons represent the SINE Alu elements. Alu RNAs are targeted by adenosine deaminases acting on RNA (ADARs), which catalyse A-to-I RNA editing. This process plays a critical role in multiple diseases, including cardiovascular disease, neurological disorders, and cancer. As part of long non-coding RNA, Alus can reversibly influence transcription and translation. The production of certain SINE RNAs increases during cellular stress, viral infection and malignant transformation. These non-coding transcripts are also components of exosomes and play an important, yet not fully understood, role in the pathogenesis of many diseases.

PhD. program Animal Physiology

Faculty of Natural Sciences of Comenius University in Bratislava

• Consequences of combined therapy of maternal depression on rat offspring
  Dôsledky kombinovanej terapie materskej depresie na potomstvo potkanov
  Name of the supervisor: prof. RNDr. Ľubica Lacinová, DrSc.
  Anotation:
  The work will focus on the consequences of drug-resistant depression and its treatment during pregnancy on the brain development of the offspring. For this type of depression, a combination of antidepressants is used. We will use the antidepressants aripiprazole (ARI) and ARI in combination with sertaline (SER). We will compare the functional brain development and neurobehavioral consequences in the offspring of rats of both sexes, while evaluating the impact of maternal depression alone and the impact of ARI and ARI+SER treatment. We will focus on the hippocampus and changes in its electrical excitability, in neurogenesis, biochemical, and structural changes.

• Characterization of proteins of the mammalian reproductive system and gametes
  Charakterizácia proteínov pohlavného systému a gamét cicavcov
  Name of the supervisor: RNDr. Jana Antalíková, 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 two mammal models (cattle and rat), by immunohistochemical and biochemical methods, or molecular biology methods.

• Neuronal-cardiac crosstalk in Dravet syndrome.
  Mechanizmy neuronálno-srdcového prepojenia v Dravetovom syndróme
  Name of the supervisor: Mgr. Bohumila Jurkovičová Tarabová, PhD.
  Anotation:
  Dravet syndrome (DS), a severe childhood epilepsy caused primarily by SCN1A mutations, is associated with a dramatically elevated risk of sudden unexpected death in epilepsy (SUDEP). While seizures are central to the disorder, increasing evidence implicates cardiac dysfunction in SUDEP pathogenesis. The proposed PhD thesis aims to investigate the cardiac and neuronal phenotype of DS using patient-derived induced pluripotent stem cells (iPSCs). The goal is to establish a pathophysiological link between SCN1A dysfunction, cardiac and neuronal excitability, and SUDEP risk, providing new insights for therapeutic strategies. Experimental work will combine electrophysiology (patch-clamp, MEA) , advanced confocal microscopy and molecularbiology methods.

• The novel psychoactive cannabinoid hexahydrocannabinol (HHC): molecular and electrophysiological characterization of its effects in the nervous system
  Nový psychoaktívny kanabinoid hexahydrocannabinol (HHC): molekulárna a elektrofyziologická charakterizácia jeho účinkov v nervovom systéme
  Name of the supervisor: RNDr. Katarína Ondáčová, PhD.
  Anotation:
  Hexahydrocannabinol (HHC) is a novel semi-synthetic cannabinoid derived from naturally occurring cannabinoids. Its psychoactive effects have been observed following consumption, predominantly among young adults. Although HHC is known to bind to cannabinoid receptors, its downstream signaling pathways and its influence on neuronal excitability have not yet been systematically investigated. This study aims to elucidate the effects of HHC on cannabinoid receptors, neuronal firing properties under in vitro conditions, and its impact on brain function in vivo.

• Polymeric nanoparticles carrying mRNA in the treatment of acute central nervous system injury and their biodegradation in the organism
  Polymérne nanočastice nesúce mRNA pri liečbe akútneho poškodenia centrálneho nervového systému a ich biodegradácia v organizme
  Name of the supervisor: RNDr. Katarína Ondáčová, PhD.
  Anotation:
  Nanomedicine currently represents a significant therapeutic potential in the treatment of a wide range of diseases. Acute injury of the central nervous system (CNS) constitutes a serious medical and socio-economic problem, particularly due to the limited regenerative capacity of the CNS. The aim of this study is to investigate whether polymeric nanoparticles carrying mRNA encoding a specific protein, or alternatively a therapeutic compound itself, are capable of influencing the regeneration of damaged CNS tissue and to elucidate the mechanisms underlying these effects. Furthermore, the analysis of the biodegradation of polymeric nanoparticles will contribute to a better understanding of their biodistribution and behavior within the organism.

• Effects of low-frequency ultrasound in wounds treatment tested in Japanese quail CAM model
  Účinky nízkofrekvenčného ultrazvuku pri liečbe rán testované na modeli CAM prepelice japonskej
  Name of the supervisor: Mgr. Mariana Máčajová, PhD.
  Anotation:
  Currently, the treatment of infected wounds is also a major challenge in medicine. At a time of increasing antibiotic resistance, alternative therapies are also coming into their own. Sonodynamic therapy is an emerging therapeutic procedure combining ultrasound and a chemical agent - a sonosensitiser. After its activation by ultrasound, reactive oxygen molecules (ROS) are produced in the tissue and have a cytotoxic effect on the surrounding cells. Sonodynamic therapy has potential applications in the treatment of cancer, superficial bacterial and yeast infections, and other pathological conditions. The aim of this dissertation will be to establish an in vivo model for the investigation and treatment of superficial infections. We will apply sonodynamic therapy using low frequency ultrasound to a quail chorioallantoic membrane (CAM) model that will be infected with bacteria and yeast. After therapy, we will monitor angiogenic changes in CAM tissue, expression of selected genes, as well as histological and immunohistochemical changes.

• Effect of acute or chronic stress on intracellular Ca2+ signaling pathway
  Vplyv akútnej a chronickej stresovej záťaže na vnútrobunkovú Ca2+ signálnu dráhu
  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 chronic exposure happens even before the birth (e.g. prenatal stress). 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. These findings suggest that during chronic stress, the same signaling pathways are affected in both the brain and the heart. In contrast to chronic stress, acute stress is an evolutionarily important adaptive response to threat, termed the ‘fight-or-flight’ response. However, in the presence of point mutations in the intracellular Ca²⁺ channel (ryanodine receptor), the acute stress response poses a significant risk for cardiac arrhythmias. The molecular mechanisms of this arrhythmogenic disorder, which is symptomatically manifested only during emotional stress or physical activity, are not well understood. The objective of the PhD thesis is to conduct a comprehensive investigation of the remodeling of intracellular Ca²⁺ signaling pathway, which translates diverse stimuli into specific cellular responses. Particular emphasis will be placed on the effects of prenatal stress on the interplay between glucocorticoid (stress hormone) and Ca²⁺ signaling pathways in the heart and brain of adult male and female rats (in vivo model of stress). Additionally, the effects of acute stress will be examined in an in vitro stress model at the level of single ryanodine receptors. The primary experimental approach will combine in vitro electrophysiological techniques with a range of complementary biochemical methods.

PhD. program Genetics/Biochemistry

Faculty of Natural Sciences of Comenius University in Bratislava

• Phosphatidylglycerol and its role in the regulation of gene expression
  Fosfatidylglycerol a jeho úloha v regulácii expresie génov
  Name of the supervisor: Mgr. Mária Balážová, PhD.
  Anotation:
  Phosphatidylglycerol is a mitochondrial lipid whose role in yeast has been overlooked until now. However, we have recently discovered that this lipid is involved in regulating the activities of enzymes synthesizing important mitochondrial lipids. The aim of the dissertation will be to determine whether phosphatidylglycerol plays a role in regulating the expression of genes encoding mitochondrial proteins and, conversely, whether sirtuins (proteins that also regulate mitochondrial biogenesis) can influence the biosynthetic pathway of phosphatidylglycerol synthesis.

• Lipid droplets: Guardians of cellular health
  Lipidové kvapôčky: Strážcovia bunkového zdravia
  Name of the supervisor: Mgr. Martin Valachovič, PhD.
  Anotation:
  Lipid droplets are depot organelles known for storing energy or membrane lipids. In our laboratory, we investigate another intriguing function of these organelles: the sequestration of toxic compounds. Our primary focus is on atypical, potentially harmful sterols that accumulate in cells during antifungal treatment. We aim to uncover the answer to the question: "How does a cell recognize a harmful lipid?"

• Lipid transfer proteins in the malaria causing parasite Plasmodium falciparum
  Proteíny prenášajúce lipidy u pôvodcu malárie Plazmodium falciparum
  Name of the supervisor: RNDr. Peter Griač, DrSc.
  Anotation:
  We will test lipid transfer proteins (LTPs) of the malaria causing parasite Plasmodium falciparum as a novel target for antimalarial drugs. We plan to investigate which lipids are transfered by the way of these LTPs. We will prepare a yeast model, expressing selected P. falciparum LTPs with the goal to test inhibitors against these LTPs.

• 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.

• The role of mitochondria in the inflammatory response
  Úloha mitochondrií v zápalovej odpovedi
  Name of the supervisor: Mgr. Mária Balážová, PhD.
  Anotation:
  Mitochondria play a critical role in regulating the inflammatory response by producing reactive oxygen species (ROS) and influencing immune signaling pathways. Dysregulated mitochondrial function can lead to excessive inflammation, contributing to chronic diseases such as arthritis and cardiovascular disorders. Understanding the interplay between mitochondria and inflammation offers exciting opportunities for the development of targeted therapies to treat inflammatory conditions.

PhD. program Microbiology

Universtity 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.

• Postbiotics - an effective approach to inactivate undesirable microbiota in animals
  Postbiotiká – účinný prístup na inaktiváciu nežiaducej mikrobioty u zvierat
  Name of the supervisor: MVDr. Monika Pogány Simonová, PhD
  Anotation:
  Antibiotic resistance is a global, still current problem in humans and animals. Despite efforts to replace synthetic antibiotics (ATB), especially in animal production, with natural additives providing prophylactic but also medicinal effects, there is a high percentage of ATB-resistant bacterial strains. Carbapenem-resistant enterobacteria, methicillin-resistant staphylococci and vancomycin-resistant enterococci/staphylococci, represent a particularly big problem. Therefore, new substances are continuously being sought to reduce the occurrence and transmission of these bacteria, but also to alleviate the ecological burden, since a large number of them are excreted into the environment and wild animals also become vectors or reservoirs. Postbiotics represent an innovative approach for inactivation/inhibition of undesirable microbiota, as they are preparations of non-living microorganisms and/or their components that provide health benefits to the host, i.e. metabolites of beneficial bacteria – bacteriocins (antimicrobial proteins), or substances extracted from the bacterial cell wall after its destruction. The main goal of the dissertation will be the isolation, selection and target a group of undesirable and/or potentially pathogenic bacterial strains, multi-resistant (with an emphasis on vancomycin resistance) bacteria from the genera Staphylococcus and Enterococcus from various animal species and their characterization (resistance to antibiotics, presence of virulence factors, ability to form biofilms, enzyme activity). In vitro testing of the antimicrobial and antibiofilm effect of postbiotics-bacteriocins tested and characterized at the CBs SAS IAP (Košice) on this undesirable and multiresistant microbiota, as well as their application in animals as part of a model experiment (mice, rabbits), will expand basic information about the antimicrobial spectrum of these bioactive substances in laboratory conditions, but also about their direct effect in the animal organism (microbiological status, immunological, biochemical and physiological parameters).

• 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 Zoology and Animal Physiology

Faculty of Science, Pavol Jozef Šafárik University in Košice

• Molecular mechanisms of early embryo cell responses to the factors of environment
  Molekulárne mechanizmy reakcií skorých embryonálnych buniek na faktory prostredia
  Name of the supervisor: RNDr. Štefan Čikoš, DrSc.
  Anotation:
  The mammalian preimplantation embryo (i.e. the embryo in the period from oocyte fertilization to implantation of blastocyst into uterus) can finish its development to the blastocyst stage relatively autonomously and in in vitro conditions in relatively simple culture media. On the other hand, recent data indicate that disturbed maternal environment significantly affects developmental potential of oocytes, quality of pre-implantation embryos, success of implantation and can be the cause of unsuccessful pregnancies in both humans and animals. Moreover, in line with the DOHaD (Developmental Origin Health and Diseases) hypothesis, impairment of early embryonic development can also have long term consequences for health in adulthood. The research will mainly focus on the role of low molecular weight ligands and their receptors. The experiments will mostly use a mouse model (in vivo as well as in vitro approaches, including mouse embryonic stem cells). Modern biochemical methods, molecular biology techniques as well as morphological methods will be used to analyze cell receptors, activated signaling pathways and physiological responses of early embryo cells.

• The effect of polyunsaturated fatty acids on preimplantation embryo development.
  Vplyv polynenasýtených mastných kyselín na preimplantačný vývin embryí
  Name of the supervisor: RNDr. Janka Babeľová, PhD.
  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.