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 molecules of the male reproductive system and mammalian sperm
  Charakterizácia molekúl samčieho pohlavného systému a spermií cicavcov
  Name of the supervisor: RNDr. Jana Antalíková, PhD.

• 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.

• Modulation of acetylcholine- and phenylephrine-induced vasomotor responses by plant metabolites in a CAM model
  Modulácia acetylcholínom a fenylefrínom indukovaných vazomotorických odpovedí rastlinnými metabolitmi v CAM modeli
  Name of the supervisor: RNDr. Boris Bilčík, PhD.

• Animal-based indicators of poultry welfare
  Na zvieratách založené indikátory welfaru hydiny
  Name of the supervisor: RNDr. Ľubor Košťál, CSc.

• 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. In our project, we will create an in vivo model for the research and treatment of superficial infections. We will apply sonodynamic therapy using low-frequency ultrasound on a quail chorioallantoic membrane (CAM) model. Sonodynamic therapy is a therapeutic method that combines ultrasound with the use of substances called sonosensitizers. Similar to photodynamic therapy (PDT), which uses light to activate photosensitizers, sonodynamic therapy uses ultrasound to activate the active agents and improve their penetration into cells. 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

Faculty of Natural Sciences of Comenius University in Bratislava

• Dysregulation of mitochondrial cardiolipin remodeling and its role in inflammatory and pyroptotic signaling in Barth syndrome
  Dysregulácia mitochondriálnej remodelácie kardiolipínu a jej úloha v zápalovej a pyroptotickej signalizácii pri Barthovom syndróme
  Name of the supervisor: Mgr. Mária Balážová, PhD.

PhD. program Microbiology and immunology

Universtity of Veterinary Medicine and Pharmacy in Košice

• 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 many 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 targeting 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, and 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.