National projects

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Duration: 1. 1. 2024 - 31. 12. 2027
Evidence number: 2/0045/24
Program: VEGA
Project leader: MUDr. Grinchii Daniil, PhD.
Phosphorylation of the ryanodine receptor/Ca2+ channel as an effective regulator of inter-channel communication
Duration: 1. 1. 2024 - 31. 12. 2027
Evidence number: 2/0010/24
Program: VEGA
Project leader: Mgr. Gaburjáková Marta, PhD.
SAS cosolvers: Mgr. Gaburjáková Jana, PhD., MUDr. Paliokha Ruslan
Annotation: The ryanodine receptor (RyR)/Ca2+ channel is one of critical components implicated in muscle and neuronalCa2+ signaling. In vivo and in vitro, RyR channels self-organize into larger clusters creating highly favorableconditions for direct inter-channel communication. Molecular mechanisms of this phenomenon, which ismanifested by synchronized (coupled) gating of numerous RyR channels, are not understood at all. The projectaim is to show that in vitro induced phosphorylation of RyR channels substantially affects the appearance andstability of coupled gating in the heart. Furthermore, we are interested in the effect of chronic in vivophosphorylation of RyR channels, which has been evidenced in various pathological conditions of the heart andbrain. We assume that stabilization of coupled gating might result in significant advancements in the treatment ofchannelopathies related to RyR dysfunction; therefore, the important part of the project will be testing the effect ofa new promising drug, Rycal-S107.
DNA methylation changes accompanying the development of multidrug resistance
Duration: 1. 1. 2024 - 31. 12. 2027
Evidence number: 2/0046/24
Program: VEGA
Project leader: Mgr. Pavlíková Lucia, PhD.
SAS cosolvers: RNDr. Boháčová Viera, CSc., Ing. Husieva Valeriia, RNDr. Kšiňanová Martina, PhD., Ing. Pelegrinová Lívia, Ing. Sulová Zdena, DrSc., Mgr. Šereš Mário, PhD., Ing. Šimoničová Kristína, PhD.
Annotation: The development of multidrug resistance (MDR), mediated by the overexpression of ABC transporters, represents a real obstacle to overcome in cancer chemotherapy. The MDR phenotype is also accompanied by the activation of other defense mechanisms that protect the cell from damage by cytostatics, including those that are not substrates of ABC transporters. These mechanisms may be of dual origin. They may be directly related to the presence of ABC transporters in the cells due to common mechanisms controlling their induction, or they may have developed due to the selection pressure of cystostatics during treatment but independently of the induction of ABC transporter expression. Alterations in the methylation of promoter regions of genes, the modulation of which may be involved in the emergence of multidrug resistance, may be responsible for the wide variability in cellular responses to cytostatic-induced chemical stress and the frequently observed changes in the state of cell differentiation.
BPKMKZHPMF - Non-antibiotic approaches to control mastitis of cows with an increase in the hygiene of dairy farms conditions
Duration: 1. 7. 2023 - 30. 6. 2027
Evidence number: APVV-22-0457
Program: APVV
Project leader: RNDr. Bujňáková Dobroslava, PhD
SAS cosolvers: Augustinská Danuše, MVDr. Karahutová Lívia, PhD., MVDr. Kocúreková Tímea, Timková Iveta
Annotation: Inflammation of the mammary gland ‒ mastitis is currently one of the three main diseases encountered by dairyfarmers. The most common treatment of mastitic cows is antibiotic therapy during lactation, but also all rounddrying programmes. However, frequent use of antibiotics results in several serious problems such as lowtreatment success, and the presence of antimicrobial residues in milk. For this reason, the EU by its "Farm to Fork"strategy plans to reduce the use of antibiotics for farm animals by 50%, which is also supported by a new laweffective from January 2022, that prohibits all forms of routine use of antibiotics and zinc oxide, includingpreventative herd treatment and all round drying of cows. In Slovakia as well as in the neighboring EU countries, nomethodological procedures have been established for dairy farmers regarding the drying of cows in order to reducethe use of antibiotics. The presented project comprehensively resolves the current problems encountered by dairyfarmers focusing on practical rationalization and implementation of new procedures for diagnosis, suppression andprevention of mastitis. The introduction of new diagnostic methods for the direct and indirect determination of inflammation symptoms supplemented by analysis of dairy cows based on clinical examination and the results ofmilk utility control with the application of algorithmic models for the detection of risky cows are among the basicobjectives of the project aimed at reducing the incidence of mastitis. One of the new components of the project tobe implemented in practice in order to reduce the consumption of antibiotics will include the introduction ofselective drying programmes for dairy cows and the development of an effective lactobacilli-based protective agentfor udder treatment. A new disinfectant for complex elimination of pathogens from the environment of the milkingparlor will be designed by the research team for use in practice conditions.
FATSPOMBE - Functional analyses of TOR signaling pathway in the regulation of abiotic stress response in the fission yeast
Duration: 1. 7. 2023 - 30. 6. 2027
Evidence number: APVV-22-0294
Program: APVV
Project leader: Mgr. Bágeľová Poláková Silvia, PhD.
SAS cosolvers: Mgr. Bakošová Anetta, PhD.
Annotation: As a consequence of our modern lifestyle, each organism is at the daily basis attacked by various impairing agents, oxidants, inducing elevation of reactive oxygen species (ROS) by individual cells. Understanding the influence of those toxic elements on biochemical and physiological processes considerably contributes to specification of their toxicity. TOR kinase, a highly conserved kinase between species, belongs to the main regulators of cell growth and metabolism in response to various stresses. The aim of the proposed project is to investigate the molecular mechanism of TOR signaling in the cell defense machineries and cell cycle regulation under food toxicants acrylamide and its metabolites-induced stress, with the use of Schizosaccharomyces pombe as model system. S. pombe is a popular model organism for studies of basic biological processes. It is often referred to as “micromammal” as its genomic organization resembles that of higher eukaryotes including humans. Similar to higher eukaryotes, TORC1 and TORC2 have been identified in S. pombe. S. pombe TORC1, which contains the catalytic subunit Tor2, and TORC2, which contains Tor1 apparently have reverse, but coordinated, roles for growth, cell cycle and sexual development. Although, the role of TOR signaling in cell responses to various stresses has been intensively studied, the underlying mechanism of TORC2 and its catalytic subunit Tor1 in S. pombe in the cell protection and cell cycle regulation under stress conditions caused by food contaminants remains unclear. We aim to utilize state-of-the art research “OMIC” methods in molecular biology, genetics, spectroscopy, biochemistry, microscopy, and visualization to achieve the proposed objectives.
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Duration: 1. 7. 2023 - 30. 6. 2027
Evidence number: APVV-22-0061
Program: APVV
Project leader: Mgr. Gaburjáková Marta, PhD.
SAS cosolvers: Mgr. Bukatová Stanislava, PhD. , RNDr. Cagalinec Michal, PhD., MMedSc Dremencov Eliyahu, DrSc, Mgr. Gaburjáková Jana, PhD., MUDr. Grinchii Daniil, PhD., RNDr. Krejčíová Eva, RNDr. Mach Mojmír, PhD., MUDr. Paliokha Ruslan, RNDr. Zahradníková, ml. Alexandra, PhD., Mgr. Zvozilová Alexandra
mClicID - -
Duration: 1. 7. 2023 - 30. 6. 2027
Evidence number: APVV-22-0085
Program: APVV
Project leader: Mgr. Ševčíková Tomášková Zuzana, PhD.
SAS cosolvers: Mgr. Andelová Natália, PhD., Ing. Ferko Miroslav, PhD., Mgr. Grman Marián, PhD., RNDr. Ondáčová Katarína, PhD., Mgr. Polčicová Katarína, PhD., Ing. Poturnayová Alexandra, PhD.
Annotation: Mitochondrial chloride channels are involved in the regulation of the mitochondrial membrane potential Ψm. In in vitro conditions, it was observed that oxidative stress results in oscillations of Ψm, which leads to the shortening of the action potential on the plasma membrane of cardiomyocytes and the occurrence of arrhythmias, mediated by the production of ATP in the mitochondria. At the level of the whole heart, arrhythmias were observed as a consequence of ischemia-reperfusion. Specific ligands of the translocator protein (TSPO) prevent the occurrence of post-ischemic arrhythmias. The use of a non-specific chloride channel blocker led to the same effect. TSPO ligands inhibit the mitochondrial chloride channels at nanomolar concentrations, suggesting that the TSPO protein mediates channel block. Thus, TSPO is likely to be in close contact with the chloride channel. Mitochondrial chloride channels are well described at the electrophysiological level, but their molecular identity remains unclear. Recently, two isoforms of chloride intracellular channels (CLICs) have been shown to be localized in mitochondria. However, CLIC channels have only been described in an artificial system - overexpressed in host cells. Mitochondrial chloride channels from native membranes are assumed to be identical to one of the two mitochondrial CLIC isoform. The aim of the presented project is to verify the hypothesis that the measured native chloride channels from cardiac mitochondria are members of the CLIC family and whether the given CLIC isoform and TSPO are in close physical contact. We assume that the obtained results will help clarify the molecular identity of the mitochondrial chloride channel, which represents a significant potential target for preventing the occurrence of post-ischemic arrhythmias.
PUFA-REPRO-BOOST - Prevention of periconceptional reproductive failure in animals via supplementation of diet with various sources of polyunsaturated fatty acids
Duration: 1. 7. 2023 - 30. 6. 2027
Evidence number: APVV-22-0071
Program: APVV
Project leader: MVDr. Fabian Dušan, DrSc.
SAS cosolvers: RNDr. Babeľová Janka, PhD., RNDr. Čikoš Štefan, DrSc., RNDr. Kovaříková Veronika, PhD., PhDr. Pisko Jozef, PhD., Mgr. Rušinová Laura, MVDr. Šefčíková Zuzana, CSc., RNDr. Špirková Alexandra, PhD.
Other cosolvers: Univerzita veterinárskeho lekárstva a farmácie v Košiciach
Annotation: In recent decades, many studies have reported a worrisome decrease in the reproductive performance of farm animals. Dietary lipid supplementation can be a good strategy to reduce the extent of reproductive failure. Oilseed meals and cakes, derived from seed oil extraction, represent interesting co-products usable for such purposes. The main aim of the project will be to evaluate the effect of diet supplementation with flaxseed and camelina cake, important sources of polyunsaturated fatty acids (PUFAs), on the ability to conceive and to reduce early embryo loss in two model animals - pubertal gilts and mouse females. Experimental animals will be fed a PUFAs supplemented diet for several weeks during the preconception period. After assessment of basic reproductive parameters, biochemical alterations in the microenvironment of developing germ cells and the impact of such alterations on antioxidant activity and membrane integrity of oocytes and proliferative and reparative activity of preimlantation embryos will be evaluated. To investigate the mechanisms underlying the impact of diet supplementation, expression of relevant molecules (receptors for hormones, prostaglandins, biosynthetic enzymes, regulatory proteins, etc.) in oocytes, embryos and tissues of the reproductive tract will be assessed. Furthermore, the protective potential of diet supplementation by PUFAs in reproductive disorders related to aging and oxidative stress in vitro will be assessed. Study will bring novel information on the mechanisms underlying the impact of PUFAs on ovulation and early embryonic development. Furthemore, acquired knowledge would result in targeted use in livestock production and veterinary practice.
RETATGZPP - Use of recombinant enzymes with thioglucosidase activity for the transformation of plant glucosinolates and their analogues into biologically active substances with preventive and suppressive effect on neoplasia development
Duration: 1. 7. 2023 - 30. 6. 2027
Evidence number: APVV-22-0383
Program: APVV
Project leader: RNDr. Imrichová Denisa, PhD.
SAS cosolvers: RNDr. Bertová Anna, PhD., Ing. Kontár Szilvia, PhD., Ing. Sulová Zdena, DrSc., Ing. Šimoničová Kristína, PhD., Yoldi Vergara Alberto , MSc.
Identification of behavioural and neurobiological indicators of positive poultry welfare
Duration: 1. 1. 2023 - 31. 12. 2026
Evidence number: 2/0129/23
Program: VEGA
Project leader: RNDr. Košťál Ľubor, CSc.
SAS cosolvers: Mgr. Pichová Katarína, PhD.
Annotation: In the field of animal welfare science, there is a marked shift from negative welfare, the study of phenomena suchas fear, pain or suffering, to positive welfare. In addition to looking for indicators of positive welfare, this alsomeans looking for ways how to induce positive affective states, positive welfare. The aim of the project is to testthe possibility of inducing positive welfare in poultry by anticipation of reward, positive contrast in the magnitudeof reward or positive control of animals over their environment or resources. We will test the possibilities ofautomating behavioural recording as an important indicator of welfare and the hypothesis that the intensity ofneurogenesis in the hippocampus may serve as a marker of cumulative affective experience.
Infrared thermography as a tool for the study of emotions and animal welfare
Duration: 1. 1. 2023 - 31. 12. 2026
Evidence number: 2/0105/23
Program: VEGA
Project leader: Mgr. Pichová Katarína, PhD.
SAS cosolvers: RNDr. Bilčík Boris, PhD., RNDr. Košťál Ľubor, CSc.
Annotation: Thanks to the massive development of new technologies in recent years these have also become a part ofagricultural production. Precision Livestock Farming (PLF) represents a new system of animal farm productionwhich applies technologies to monitor the health and welfare of animals to improve the production and quality oflife of the animals. Infrared thermography, due to its non-invasiveness, represents a potential tool to measure thewelfare of poultry from several perspectives, whether assessing external indicators such as the degree ofplumage damage, but also physiological parameters detecting affective states through changes in temperature ofperipheral body regions. The aim of the project is to optimize the use of infrared thermography to assess welfarein laying hens, to test its application in commercial breeding conditions, and thus contribute to the development ofparameters objectively assessing the quality of life of animals.
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Duration: 1. 1. 2023 - 31. 12. 2026
Evidence number: 2/0051/23
Program: VEGA
Project leader: Mgr. Ševčíková Tomášková Zuzana, PhD.
SAS cosolvers: RNDr. Ondáčová Katarína, PhD.
Annotation: Cardiac arrhythmias are one of the most common causes of death in the world. Arrhythmias also arise as a result of ischemia/reperfusion, when changes in nutrient and oxygen supply occur. Oxygen radicals may increase during reperfusion. Both metabolic and oxidative stress have been shown to result in arrhythmias due to cyclic changes in the mitochondrial membrane potential. These changes are mediated by chloride channels, which are thought to be identical to the CLIC5 isoform of intracellular chloride channels. Cardioprotective effects at the level of cells and the whole heart were observed after application of a specific ligand of mitochondrial translocator protein TSPO - 4-chlorodiazepam (4Cl-DZP), but also after application of a non-specific anion channel inhibitor. 4Cl-DZP is thought to act on chloride channel activity indirectly, via the TSPO protein, but no details of this interaction are known. The aim of our project is to describe the relationship between CLIC5 chloride channels and the TSPO receptor.
Molecular mechanisms of preimplantation embryo responses to environmental factors
Duration: 1. 1. 2023 - 31. 12. 2026
Evidence number: 2/0041/23
Program: VEGA
Project leader: RNDr. Čikoš Štefan, DrSc.
SAS cosolvers: RNDr. Babeľová Janka, PhD., MVDr. Fabian Dušan, DrSc., RNDr. Kovaříková Veronika, PhD., PhDr. Pisko Jozef, PhD., Mgr. Rušinová Laura, MVDr. Šefčíková Zuzana, CSc., RNDr. Špirková Alexandra, PhD.
Annotation: The project deals with the preimplantation embryo development, focusing on the mechanisms by which the early embryo responds to environmental factors. The role of selected cellular receptors will be investigated with emphasis on possible interactions between receptors activated by the same or by concurrent ligands (glutamate, glycine, GABA, selected insecticides). The impact of receptor ligand transporters will also be investigated. Selected intracellular signaling molecules and processes involved in the activation of the identified receptors as well as possible alternative mechanisms (such as oxidative stress) activated by the action of the investigated ligands will be analyzed. Understanding the mechanisms by which environmental factors affect the development of the preimplantation embryo can contribute to the development of husbandry, nutrition and animal health management practices that lead to a reduction of economic losses in livestock production caused by earlyembryo loss or later health disorders.
Lipid transfer proteins – study of molecular mechanisms and their potential as targets in treatment of selected human diseases.
Duration: 1. 1. 2023 - 31. 12. 2026
Evidence number: 2/0047/23
Program: VEGA
Project leader: RNDr. Griač Peter, DrSc.
SAS cosolvers: Ing. Pokorná Lucia, Šťastný Dominik, M.Sc., RNDr. Tahotná Dana, CSc.
Annotation: The aim of the project is to investigate the molecular mechanisms of selected lipid-transfer proteins and thepossibilities of their use as targets for the treatment of human diseases caused by microorganisms and parasites.We will focus on two types of diseases: those caused by yeast and fungi, and malaria caused by the protozoanPlasmodium falciparum. The absence of phosphatidylinositol transfer protein (PITP) Pdr16 causes an increase inthe susceptibility of yeast microorganisms to clinically used antifungals. To understand why, we will investigate ina model organism, the yeast Saccharomyces cerevisiae, the physiological role and molecular mechanism ofaction of the Pdr16 protein and its closely related Pdr17 protein. In P. falciparum, we will study two PITPs with theCRAL-TRIO structural domain that these proteins share with S. cerevisiae Sec14p. We will take advantage of theknowledge that Sec14p can be inhibited by molecules, some of which are under clinical investigation as potentialantifungals.
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Duration: 1. 1. 2023 - 31. 12. 2026
Evidence number: 2/0030/23
Program: VEGA
Project leader: prof. Ing. Breier Albert, DrSc.
SAS cosolvers: RNDr. Bertová Anna, PhD., RNDr. Boháčová Viera, CSc., RNDr. Imrichová Denisa, PhD., Ing. Kontár Szilvia, PhD., RNDr. Kšiňanová Martina, PhD., Mgr. Pavlíková Lucia, PhD., Ing. Pelegrinová Lívia, Ing. Sulová Zdena, DrSc.
Elucidation of the function of selected genes in meiotic division in the yeast Schizosaccharomyces pombe
Duration: 1. 1. 2023 - 30. 12. 2026
Evidence number: 1/0340/23
Program: VEGA
Project leader: Mgr. Bágeľová Poláková Silvia, PhD.
SAS cosolvers: Mgr. Bakošová Anetta, PhD.
Other cosolvers: Prof.
Characterization of excitatory and inhibitory neurons in the brain areas relevant for development of social behaviour in the autismrelated model
Duration: 1. 7. 2022 - 30. 6. 2026
Evidence number: APVV-21-0189
Program: APVV
Project leader: Mgr. Jurkovičová Tarabová Bohumila, PhD.
SAS cosolvers: Ing. Dubiel Lucia, PhD., prof. RNDr. Lacinová Ľubica, DrSc., Mgr. Ševčíková Tomášková Zuzana, PhD.
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Duration: 1. 7. 2022 - 30. 6. 2026
Evidence number: APVV-21-0473
Program: APVV
Project leader: Mgr. Gaburjáková Marta, PhD.
SAS cosolvers: Mgr. Gaburjáková Jana, PhD.
ALTZINC - Potential and prospect of alternative zinc sources in animal nutrition
Duration: 1. 7. 2022 - 30. 6. 2026
Evidence number: APVV-21-0301
Program: APVV
Project leader: RNDr. Čobanová Klaudia, PhD.
SAS cosolvers: RNDr. Batťányi Dominika, PhD., Mgr. Bombárová Alexandra, RNDr. Bujňáková Dobroslava, PhD, prof. MVDr. Faix Štefan, DrSc., MVDr. Grešáková Ľubomíra, PhD., MVDr. Kocúreková Tímea, MVDr. Mikulová Klára, Ing. Petrič Daniel, PhD., RNDr. Takácsová Margaréta, PhD., MVDr. Váradyová Zora, PhD
Annotation: The presented project proposal is focused on the use of various zinc nanoparticles and organic zinc sources as mineral supplements in animal nutrition and their effect on microelements absorption, retention, and utilisation in ruminants and poultry. Investigation of the effects of various dietary zinc sources on physiological processes and microbial parameters of the gastrointestinal tract of ruminants and poultry should bring new principal results. In general, the experiments will be aimed at improving the mineral status and optimising digestive processes in farm animals in an effort to reduce zinc excretion and thus environmental pollution of minerals from animal production. Research on the distribution of specific zinc-containing metalloproteins in animal tissues and their dependence on appropriate delivery of zinc in the form with high bioavailability may provide us with new basic information which in turn may be useful in practice for better prevention of oxidative stress and its negative consequences. The impact of various zinc nanoparticles in the animal feed on the quality of products of animal origin will be investigated as well. The basic knowledge obtained by fulfilling of objectives of the proposed project should also lay the foundation for future applied research on the supplementation of feeds with bioavailable zinc sources in order to improve animal health and performance.
DRPGE - The role of DNA repair proteins in gene repression
Duration: 1. 7. 2022 - 30. 6. 2026
Evidence number: APVV-21-0210
Program: APVV
Project leader: Mgr. Bágeľová Poláková Silvia, PhD.
SAS cosolvers: Mgr. Bakošová Anetta, PhD., Mgr. Balážová Mária, PhD., Ing. Čipák Ľuboš, PhD., Ing. Čipáková Ingrid, PhD., Mgr. Holič Roman, PhD., Mgr. Valachovič Martin, PhD.
Annotation: Eukaryotic cells have evolved two mechanistically distinct pathways to repair double-strand breaks during mitosis: non-homologous end joining (NHEJ) and homologous recombination (HR). More recently, HR proteins have been shown to play critical roles in maintaining genome integrity during DNA replication. Additionally, our latest research showed that Dbl2 protein along with other HR proteins act in concert with HIRA histone chaperone to assemble repressive chromatin near hard-to-replicate sites. Notably, cells lacking either HR proteins or HIRA factors exhibited increased levels of antisense RNA and RNA from the LTR retrotransposons and subtelomeric genes. Furthermore, the localization of the misregulated genes significantly correlated with repetitive DNA elements such as LTRs. However, the mechanism underlying this phenomenon remains largely unknown. In this project, we propose that the observed repression of gene expression is an integral part of the recombination-dependent replication pathway. We postulate that Sap1 binding to LTRs blocks replication fork progression and results in stalled or collapsed replication forks. Collapsed replication forks are remodeled and relocated to nuclear periphery. The relocation of damaged DNA to nuclear periphery can provide an access to a set of factors necessary for particular pathways of DNA repair. At nuclear periphery both imprecise NHEJ and break-induced replication pathways are favored. After the repair, the affected hard-to-replicate sites might be quickly silenced by factors such as HIRA to avoid a toxic gene expression. In this project, we intend to use classical genetics, high-resolution microscopy and advanced methods based on whole genome sequencing such as MNase-seq and ChIP-seq to obtain a more quantitative picture of chromatin dynamics. We believe that the findings of this research will have broad implications to the field of cancer research and cell division.
Biotechnological potential of nonconventional yeast in the production of squalene
Duration: 1. 1. 2022 - 31. 12. 2025
Evidence number: 2/0036/22
Program: VEGA
Project leader: Mgr. Garaiová Martina, PhD.
SAS cosolvers: Mgr. Holič Roman, PhD., Mgr. Krajčiová Daniela
Annotation: Ergosterol biogenesis in yeast has been studied so far mainly in Saccharomyces cerevisiae traditionally used inbasic research and industry. It is quite surprising that very little is known about sterol homeostasis even in thelarge group of so-called nonconventional oleagionus yeasts utilized as producing organisms for various valuablelipids. The project is aimed at the study of sterol homeostasis in oleaginous yeasts Yarrowia lipolytica andRhodosporidium toruloides and on the role of lipid droplets in this process. Using the methods of metabolicengineering we will evaluate the potential of these yeasts in production of squalene, a precursor in ergosterolbiosynthesis with applications in cosmetic and pharmaceutic industry. We will also try to identify othernonconventional yeast species able to accumulate high amounts of squalene. The results of the project shouldcontribute to the extension of the basic knowledge about the mechanisms and biotechnological applications oflipid accumulation in yeasts.
Smart deep brain stimulation as a treatment strategy in treatment-resistant depression
Duration: 1. 1. 2022 - 31. 12. 2025
Evidence number: 2/0057/22
Program: VEGA
Project leader: MMedSc Dremencov Eliyahu, DrSc
SAS cosolvers: MUDr. Grinchii Daniil, PhD., MUDr. Paliokha Ruslan, Ing. Mgr. Rosipal Roman, DrSc., Mgr. Rošťáková Zuzana, PhD.
Other cosolvers: Ladis
Annotation: Impaired connectivity between different brain areas underlines pathophysiology of multiple brain disorders. It is possible that impaired connectivity between prefrontal cortex and ventral pallidum is involved in depression. Smart deep brain simulation, combining real-time detection of the neuronal activity in in prefrontal cortex with the stimulation of ventral tegmental area, might be thus an effective in depression. We aim to examine the cortico-tegmental connectivity and to test the antidepressant-like effectiveness of the smart deep brain stimulation in an animal model of depression.
NANOREDUMET - Zinc feed additives as a strategy to reduce methane emissions in ruminants with endoparasites
Duration: 1. 1. 2024 - 31. 12. 2025
Evidence number: SK-PL-23-0004
Program: APVV
Project leader: MVDr. Váradyová Zora, PhD
SAS cosolvers: RNDr. Batťányi Dominika, PhD., Mgr. Bombárová Alexandra, RNDr. Čobanová Klaudia, PhD., Ing. Petrič Daniel, PhD.
Annotation: Recent data indicate that agriculture accounts for substantially of all emissions of greenhouse gases globally, and reducing emissions is one of the biggest challenges in ruminant production systems. Most of the anthropogenic methane emissions are from ruminant enteric fermentation, so reducing global methane emissions from animal production is necessary, with international commitments linked to efforts to combat climate change factors. Parasitic worms of ruminants, such as gastrointestinal nematodes, influence several factors associated with methane emissions, including feed efficiency, nutrient use, and animal production. The proposed concept of this bilateral cooperation project focuses on investigating the anti-methanogenic effects of feed supplementation with zinc oxide nanoparticles on lambs infected with gastrointestinal nematodes. The search for information will lead to a better understanding of the environmental costs caused by parasitic diseases.
Modulation of neuronal excitability by homocysteine
Duration: 1. 1. 2022 - 31. 12. 2025
Evidence number: 2/0081/22
Program: VEGA
Project leader: prof. RNDr. Lacinová Ľubica, DrSc.
SAS cosolvers: Ing. Dubiel Lucia, PhD., MUDr. Grinchii Daniil, PhD., Ing. Idunková Alžbeta, Mgr. Jurkovičová Tarabová Bohumila, PhD., Mgr. Ševčíková Tomášková Zuzana, PhD., Mgr. Tomko Matúš, PhD.
Annotation: Homocysteine (Hcy) is an intermediate of methionine metabolism physiologically presents in the plasma of healthy humans. Abnormally high plasma level of Hcy results in a metabolic condition called hyperhomocysteinemia (hhc). It is related to cardiovascular and neurological disorders including dementia, Parkinson’s disease, multiple sclerosis, epilepsy, and peripheral neuropathy. We will analyse the effect of hhc on the modulation of neuronal excitability at the level of single neurons and neuronal networks. Alteration of voltage-activated Na+, K+, and Ca2+ currents and ligand-gated glutamate and GABA receptors will be investigated in cultured primary thalamic neurons. The involvement of Ca2+ channel isoforms will be assessed in detail with the aim to clarify the underlying mechanisms. Finally, complex effects of changes in voltage- and ligand-gated channels on action potential firing will be characterized. The project will contribute to understand the mechanisms underlying neuropathologies related to hhc.
The effect of UV-B radiation on DNA damage and repair mechanisms in the P-glycoprotein-expressing L1210 cell line
Duration: 1. 1. 2022 - 31. 12. 2025
Evidence number: 2/0141/22
Program: VEGA
Project leader: Mgr. Šereš Mário, PhD.
SAS cosolvers: RNDr. Boháčová Viera, CSc., Ing. Kavcová Helena, RNDr. Kšiňanová Martina, PhD., Ing. Kyca Tomáš, PhD., Mgr. Pavlíková Lucia, PhD., Ing. Sulová Zdena, DrSc.
RNA structural determinant of Alus exonization
Duration: 1. 1. 2022 - 31. 12. 2025
Evidence number: 2/0016/22
Program: VEGA
Project leader: Mgr. Královičová Jana, PhD.
SAS cosolvers: Ing. Borovská Ivana, PhD.
The role of phosphatidylglycerol in attenuation of inflammation
Duration: 1. 1. 2022 - 31. 12. 2025
Evidence number: VEGA 2-0030-22
Program: VEGA
Project leader: Mgr. Balážová Mária, PhD.
Annotation: In the context of current SARS-CoV-2 infections and accompanying pulmonary complications, attention needs to be focused on all aspects of the respiratory system. The virus is causing damage to type II alveolar cells, thus drastically reducing the production of lung surfactant lipids and proteins that are essential for respiration and their secretion into alveolar space. Understanding the defense mechanisms of the lungs plays a crucial role in responding to infection. One of the critical consequences of SARS-CoV-2 infection is the development of acute respiratory distress syndrome (ARDS). The main objective of this project is to contribute to the knowledge about the potential use of valproic acid to induce the synthesis of phosphatidylglycerol in the pulmonary surfactant. We hypothesize that intracellularly increased phosphatidylglycerol level could suppress inflammatory responses in our A549 alveolar tumor cell model and similarly in patients with ARDS.
Physiopathology of T-type calcium channels in motor neuron function
Duration: 1. 1. 2022 - 31. 12. 2025
Evidence number: 2/0073/22
Program: VEGA
Project leader: dr. Weiss Norbert, PhD.
SAS cosolvers: Ing. Dubiel Lucia, PhD., Ing. Idunková Alžbeta, Mgr. Jurkovičová Tarabová Bohumila, PhD., prof. RNDr. Lacinová Ľubica, DrSc., Mgr. Tomko Matúš, PhD.
Nano-Neuro-Plast - Activation of the VGF/BDNF/TrkB pathway by synthetic mRNA encapsulated in polyplex nanoparticles: effects on neural excitability, neuroplasticity and animal behavior
Duration: 1. 7. 2021 - 30. 6. 2025
Evidence number: APVV-20-0202
Program: APVV
Project leader: MMedSc Dremencov Eliyahu, DrSc
SAS cosolvers: Mgr. Cagala Martin, Mgr. Gaburjáková Jana, PhD., Mgr. Gaburjáková Marta, PhD., MUDr. Grinchii Daniil, PhD., prof. RNDr. Lacinová Ľubica, DrSc., Mgr. Macková Katarína, PhD., Mgr. Niederová-Kubíková Ľubica, PhD.
Annotation: Neuroplasticity is the ability of the central nervous system (CNS) to change and adapt throughout the life through its structural and/or functional reorganization. Brain plasticity is essential for the normal CNS function, while several CNS disorders, such as depression and schizophrenia, are accompanied by decreased neuroplasticity. Neurotrophic growth factors, such as brain derived neurotrophic factor (BDNF), VGF, and fibroblast growth factor 2 (FGF2) play a key role in neuroplasticity. We will examine, for the first time, the effect of a non-invasive intra-CNS delivery of messenger RNA (mRNA) encoding these factors on neuronal excitability, plasticity, and animal behavior. Fluorescently labeled mRNA will be encapsulated in polyplex nanomicelles and administered intranasally. The incorporation of mRNA within the CNS will be assessed using STED microscopy. The effect of the exogeneous growth factor mRNA will be examined on neuronal excitability using in vitro and in vivo electrophysiology, on neurogenesis using the fluorescent immunohistochemical staining, on dendrito- and synaptogenesis using electron microscopy, on endogenous mRNA and protein expression-using the real-time PCR and Western blot analysis, and on intracellular calcium signaling using the method of planar lipid membranes. The effect of exogenous growth factor mRNA on the specific characteristic of animal behavior (cognition, social interacting, and anxiety) will be attested using appropriate behavioral tests. We expect that the polyplex nanomicelles to be designed will deliver mRNA encoding neurotrophic factors to the deep brain areas, with subsequent induction of pro-neuroplastic, pro-cognitive, anxiolytic and antidepressant-like effects. This non-invasive way of administration of a therapeutic mRNA into the brain might be used in the future as a next generation treatment strategy in depressive and psychotic disorders.
GLYCO4BIO - Biochip systems for targeted glycan analysis of biomarkers for biomedical and biotechnological applications
Duration: 1. 7. 2021 - 30. 6. 2025
Evidence number: APVV-20-0243
Program: APVV
Project leader: Ing. Sulová Zdena, DrSc.
SAS cosolvers: RNDr. Bertová Anna, PhD., RNDr. Imrichová Denisa, PhD., Ing. Kontár Szilvia, PhD.
Annotation: The GLYCO4BIO project focuses on research and development of analytical systems based on microarraybiochips enabling targeted and high-throughput glycoprofiling and their use in biomedicine and biotechnology. Thisis a strongly interdisciplinary research with a high degree of innovation, especially in the field of construction andapplication of original biochip devices on the microarray platform. New systems for analyzing glycan structures invarious types of biological samples will be developed, verified and validated, such as a high-performancemicrofluidic reflectometric label-free microarray system, and an on-chip glycoprofiling platform combiningmicroarray and MS technology. The expected benefit of the presented project is mainly in the development ofinnovative biochip systems for targeted glycorecognition based on modern technologies and their use inbiomedicine, biotechnology, the study of biointeractions and in the analysis and screening of biomarkers. Thesystems will be applied, for example, in the research and detection of biomarkers of congenital disorders ofglycosylation (CDG), cancer, gestational diabetes, in oncological research, as well as in the development andcharacterization of the therapeutic proteins. The developed biochip systems significantly outperform traditionaltechniques and have a high potential for their translation into clinical analysis. The expected results of the projectwill improve and expand the possibilities of diagnostics and therapy, and significant benefits are also expected inthe expansion of knowledge in the field of biomedical research, glycoproteomics and biotechnology.
RENASTHERA - Novel renal antisense therapy platform for CKD
Duration: 1. 8. 2021 - 30. 6. 2025
Evidence number: APVV-20-0494
Program: APVV
Project leader: Ing. Poturnayová Alexandra, PhD.
Annotation: Chronic kidney disease (CKD) with its progressive nature towards end-stage renal disease (ESRD) is a lethal andrapidly progressing severe health complication associated with significantly decreased quality of life and highmortality rates. Strikingly, despite the progress made in early-diagnostics of CKD, state-of-the-art therapeutics donot significantly decrease the risk of renal and cardiovascular morbidity and mortality rates in CKD patients whichremain devastatingly high. This fact highlights an urgent need not only for novel therapeutics but also for theimplementation of progressive experimental and clinical tools into translational drug discovery. In this context, theproposed RENASTHERA project offers a novel therapeutic solution to stop progressive renal function loss. Thissolution is based on a patented method of nucleic acid inhibition. Periostin, a 90 kDa secreted protein wasidentified as a key player in CKD development, inhibition of which effectively prevented CKD progression. Thedesign, synthesis, and functional validation of an RNA inhibitor specifically designed for periostin RNA is thus theclearly defined scope of the proposed RENASTHERA project.
NONBOVQUAL - Evaluation method of raw goat milk microbiological quality and use of autochthonous lactic acid bacteria at non-bovine Milk processing
Duration: 1. 7. 2021 - 30. 6. 2025
Evidence number: APVV-20-0204
Program: APVV
Project leader: MVDr. Lauková Andrea, CSc.
SAS cosolvers: MVDr. Bino Eva, PharmDr. Focková Valentína, PhD., MVDr. Pogány Simonová Monika, PhD, RNDr. Ščerbová Jana, PhD.
Annotation: The aim of the project submitted is to increase products quality made from non-bovine milks (ewes and goat). The value of total cell count in non bovine milk is their basic statutory indicator. In the past, a speedy routine method based on laser flow cytometry was introduced in Slovak practice for microbiolgical quality evaluation of raw ewes milk. This method proved to be beneficial for ewes milk producers and processors. However, for the evaluation of raw goat milk quality, solely the lenghty assigned cultivation method is still used. Therefore, the project aims to design a conversion formula specific for Slovakia to measure raw goat milk microbiological quality mean of laser flow cytometry method to CFU/ml which are used for statutory limits, and to the implementation of this method in practice as an accredited and authorized methods. For the improvement of dairy products quality based on non-bovine milks speedy methods which allow the separation of milk worth insufficient quality, do not constitute the only important condition. The other important condition consists in biological/bioprocessal methods of spoilage microbiota elimination during milk processing itself. Therefore, the subsequent aim of the project is the utilization of autochthonous beneficial, bacteriocin-producing lactic aicd bacteria strains with bacteriocin activity in products produced from non-bovine milks up to the implementation of such procedures in dairy processing.
IZOTIOVIVO - Molecular mechanisms of trialkyl-/triaryltin isothiocyanates\' and carboxylates\' antitumour properties - novel ligands of nuclear retinoid X receptors in rat mammary gland carcinomas and human tumour cell lines
Duration: 1. 7. 2021 - 30. 6. 2025
Evidence number: APVV-20-0314
Program: APVV
Project leader: Mgr. Šereš Mário, PhD.
SAS cosolvers: RNDr. Boháčová Viera, CSc., Mgr. Pavlíková Lucia, PhD., Mgr. Šereš Mário, PhD.
Annotation: Organometallic compounds, on account of their structural diversity, are applied in human oncology in the treatmentof cancer. Triorganotin derivatives showed significant cytotoxic properties. At the cellular level, they induce massivecell death in various types of cell cultures even at low concentrations and are able to activate the processes ofapoptotic pathways, in which several molecular mechanisms play a role. A significant breakthrough in knowledgewas our recent experimental confirmation of the ability of molecules of triorganotin compounds to bind to nuclearretinoid X receptors, and thus function as potent agonists. The aim of the present project is to investigate the in vivo effects of tributyl/triphenyltin isothiocyanates in the process of chemical carcinogenesis of the mammary glandof female rats, which is based on our current results of in vitro experiments. Simultaneously, the research ofantitumour properties of triorganotin compounds activating RXR-RAR heterodimers comprising novel RXR agonistsbased on triorganotin carboxylates, is envisaged. In vitro analyses of molecular mechanisms leading to inhibition oftumour cell growth or induction of apoptosis in the presence/absence of natural ligands of RAR receptors onhuman breast tumour cell lines: MCF-7 (non-invasive, ER positive), T47D (ER positive), MDA-MB-231 (invasive,triple negative) and MDA-MB-436 (invasive, ER negative, PR negative), will be accomplished. We also plan toachieve new data on the possible endocrine disruption of triorganotin compounds on the murine TM3 cell line andthe human COV434 cell line representing the reproductive system. We assume that the presented project will gainnew and original knowledge about the mechanism of the action of the studied substances through their binding andactivation of nuclear receptors, their transactivation as well as crosslink with other signalling pathways that maycontribute to the development of novel treatment options for breast cancer.
HiVaLip - Nonconventional yeasts as producers of high value-added lipids
Duration: 1. 7. 2021 - 30. 6. 2025
Evidence number: APVV-20-0166
Program: APVV
Project leader: Mgr. Holič Roman, PhD.
SAS cosolvers: Mgr. Garaiová Martina, PhD., RNDr. Griač Peter, DrSc., RNDr. Hapala Ivan, CSc., Mgr. Krajčiová Daniela, Mgr. Petrisková Lívia, Soni Apoorva, Mgr. Valachovič Martin, PhD.
Other cosolvers: pro
Annotation: In addition to traditional baker`s yeast Saccharomyces cerevisiae there is a large group of „nonconventional“ yeasts which have evolved specific metabolic adaptations enabling them to utilize various growth substrates. An important group of nonconventional yeasts is represented by oleaginous yeasts which are able to accumulate high amount of lipids. Due to specific lipid metabolism and ability to utilize various cheap waste products as growth substrates, several nonconventional yeast species could be used for the production of high value-added lipids. The project is focused on the potential of nonconventional yeasts for the production of two such lipids – punicic acid and squalene. Punicic acid is a polyunsaturated fatty acid present in the pomegranate seed oil. Squalene is a triterpenoid produced in eukaryotes as the intermediate in sterol synthesis. Both lipids show positive effects on human health and have thus high potential for the use in cosmetic and pharmaceutical industries and as nutraceutics or additives to functional food and feedstuff. The project will focus on the effect of heterologous expression of genes from pomegranate on punicic acid production in the yeast Schizosaccharomyces pombe and in two oleaginous yeasts Rhodotorula (Rhodosporidium) toruloides and Yarrowia lipolytica. Accumulation of squalene will be studied by applying the methods of metabolic engineering in R. toruloides and Y. lipolytica. An important aim of the project is also lipid metabolism and production of lipids in selected species of the genus Magnusiomyces and screening of nonconventional yeasts from yeast collections for their potential to produce high value-added lipids. In the identified species, the ability to utilize cheap waste substrates for growth will be determined. The results obtained within project implementation could thus extend the use of nonconventional yeasts in the biotechnological production of commercially valuable lipids.
LIPinINF - The potential role of valproic acid in attenuation of inflammation
Duration: 1. 8. 2021 - 30. 6. 2025
Evidence number: APVV-20-0129
Program: APVV
Project leader: Mgr. Balážová Mária, PhD.
Other cosolvers: Prírodovedeck
Annotation: In the context of current SARS-CoV-2 infections and accompanying pulmonary complications, attention needs to be focused on all aspects of the respiratory system. The virus is causing damage to type II alveolar cells, thusdrastically reducing the production of lung surfactant lipids and proteins that are essential for respiration and theirsecretion into alveolar space. Understanding the defense mechanisms of the lungs plays a crucial role in responding to infection. One of the critical consequences of SARS-CoV-2 infection is the development of acute respiratory distress syndrome (ARDS).The main objective of this project is to contribute to the knowledge about the potential use of valproic acid to induce the synthesis of phosphatidylglycerol in the pulmonary surfactant. To answer specific questions, we will use three models differing in their complexity – yeast (Saccharomyces cerevisiae), human tumor cell line (HAP1), and avian chorioallantoic membrane. We hypothesize that intracellularly increased phosphatidylglycerol level could suppress inflammatory responses in ARDS patients and reduce the attachment of the virus to cell surface receptors. This would mean a reduction in infectious particle transmission between individuals and significant alleviation of ARDS symptoms.
Optogenetika u s - Examining the role of dopamine and adult neurogenesis in learned behavior of songbirds using optogenetic manipulation
Duration: 1. 7. 2021 - 30. 6. 2025
Evidence number: APVV-20-0344
Program: APVV
Project leader: Mgr. Niederová-Kubíková Ľubica, PhD.
SAS cosolvers: RNDr. Bilčík Boris, PhD., Mgr. Buraľová Martina, Mgr. Hoďová Vladimíra, MUDr. Mgr. Hromádka Tomáš, PhD., RNDr. Košťál Ľubor, CSc., Mgr. Máčajová Mariana, PhD., Mgr. Pavuková Eva, PhD.
Annotation: Dopamine signaling and neurogenesis play an important role in structural and functional neuroplasticity in the adultbrain. In this project, we focus on the role of the dopaminergic neurotransmission and the role of newborn neuronsfor the control of learned motor sequences in songbirds. While there are numerous studies about motor sequencelearning with external reward such as food, studies that involve internal reward system are rare. The internalreward system has been linked with dopamine signalization, and the songbird vocal learning and productionrepresent a great model for such study since the birdsong comprises sequences of very fast actions. We proposeto use the modern technique of optogenetics to manipulate vocal sequences. The optogenetic approach enablesprecise control of neural activity in a specific brain region in a freely moving animal with millisecond precision. Herewe propose to modify dopamine reward signaling to the striatal part of basal ganglia and examine the changes inthe song sequence. The results will determine the role of dopamine reward system in birdsong learning. In thesecond part of the project, we propose to optogenetically manipulate the activity of new neurons incorporated to thebrain region necessary for song production. The number of newborn neurons in this region increases at the timewhen the song structure is more variable and new syllables are integrated to the song. We will find in the projectwhether new neurons born in adulthood are able to modify the song and whether they enable or contribute to thesong variability.
Bacteriocins and their use to reduce spoilage microbiota in animal husbandry
Duration: 1. 1. 2021 - 31. 12. 2024
Evidence number: VEGA 2/0005/21
Program: VEGA
Project leader: MVDr. Pogány Simonová Monika, PhD
SAS cosolvers: MVDr. Bino Eva, PharmDr. Focková Valentína, PhD., MVDr. Lauková Andrea, CSc., RNDr. Ščerbová Jana
Annotation: Methicillin resistance in staphylococci has had problem occuring also in animal production. Reduction and/or elimination of methicillin resistant (MetR) staphylococci in healthy breed is problem due to their multiresistance. However, utilization of antimicrobial proteinaceous substances –enterocins with a broad inhibition spectrum (produced by some strains of the genus Enterococcus) could be a promising way. In this basic research project will be therefore investigated inhibition activity of enterocins (characterized at our workplace) against a terget of faecal microbiota with impact on MetR and biofilm-forming staphylococci from various animals. Testing will be provided under in vitro as well as in vivo conditions; effect of enterocins against selected MetR strains will be verified in a model experiment by using experimental (mice) or farming (broiler rabbit) animals.
Bioactive oils in the therapy of microbial infections on avian chorioallantoic membrane
Duration: 1. 1. 2021 - 31. 12. 2024
Evidence number: 2/0042/21
Program: VEGA
Project leader: Mgr. Máčajová Mariana, PhD.
SAS cosolvers: RNDr. Bilčík Boris, PhD., MUDr. Čavarga Ivan, PhD., Mgr. Kundeková Barbora, Mgr. Meta Majlinda
Annotation: The treatment of various microbial and yeast infections is currently a major challenge in veterinary medicine. For breeders, some diseases such as mastitis, trichophytia or onychomycosis are often eradicating. Because of frequent antibiotic resistance, other treatments are emerging. In our project we will develop an in vivo model for the research of yeast and bacterial infections. We will use quail and turkey chorioallantoic membrane (CAM) to test the effects of various drugs and treatments. After validation and optimization of the model, we will topically apply bioactive substances in various concentrations and monitor their antimicrobial and biological effect. We will also monitor the additive effect of PDT using curcumin and hypericin. Angiogenic changes, expression of selected genes, histological and immunohistochemical changes after application of the substances will be examined. The obtained results will be useful in the treatment of yeast and microbial infections in animals and humans.
Nutritional and health biomarkers in farm animals
Duration: 1. 1. 2021 - 31. 12. 2024
Evidence number: 2/0008/21
Program: VEGA
Project leader: MVDr. Grešáková Ľubomíra, PhD.
SAS cosolvers: RNDr. Batťányi Dominika, PhD., RNDr. Čobanová Klaudia, PhD., RNDr. Kišidayová Svetlana, CSc., MVDr. Mikulová Klára, Ing. Petrič Daniel, PhD., Ing. Tokarčíková Katarína, PhD., MVDr. Váradyová Zora, PhD
Annotation: Proposal project is focused on the investigation of appropriate dietary and health biomarkers reflecting the dietary intake, nutritional status and biological effects of feed additives used in animal nutrition. Nutritional biomarkers are biochemical, functional, or clinical indices of animal status that reflect nutrient exposure (recent or long term), nutritional status depending on digestibility, absorption and utilisation of dietary nutrient, and nutrient metabolism/effect in animal body. Effective gastrointestinal functionality is crucial in determining animal health, welfare and performance, therefore we will focus on the biomarker determination of gastrointestinal functionality. The suitability of selected biomarkers will be tested in experiments by animal feed supplementation. The experiments will be aimed to improve the mineral status and optimize digestive processes in poultry and sheep to minimize the environmental pollution by the reduction of methanogenesis and excretion of heavy metals.
Diagnostic of oncological diseases using aptasensors: development and validation
Duration: 1. 1. 2021 - 31. 12. 2024
Evidence number: 2/0160/21
Program: VEGA
Project leader: Ing. Poturnayová Alexandra, PhD.
SAS cosolvers: Mgr. Bábelová Andrea, PhD., Ing. Domšicová Michaela, Mgr. Jakič Kristína, PhD., Ing. Kyca Tomáš, PhD., Mgr. Ševčíková Tomášková Zuzana, PhD.
Annotation: DNA aptamers, also referred to as DNA antibodies, are short single-stranded sections of DNA that form spatial structures that allow high-affinity to interact with receptors and other biomolecules. The project aims to develop and validate a new diagnostic method that utilizes the unique affinity properties of DNA aptamers for the early detection of cancer.In terms of project aims, we will analyze the molecular mechanisms of interactions between DNA aptamers and specific markers found on the surface of the tumor cells. We plan to use a sensitive method of quartz crystal microbalances (QCM), which allows real-time monitoring of interactions. For practical use, we plan to prepare conjugates of selected aptamers and gold nanoparticles depending on their physicochemical parameters and their interaction with neoplastic cells. We have the ambition to identify factors currently limiting the wider use of aptamers and aptamer-modified nanoparticles in clinical practice and contribute to their elimination.
Engineering of oleaginous yeast Rhodotorula toruloides as an efficient cell factory for punicic acid production
Duration: 1. 1. 2024 - 31. 12. 2024
Evidence number: APP0521
Program: DoktoGranty
Project leader: Mgr. Krajčiová Daniela
Expression of acetylcholine receptors in mouse preimplantation embryos
Duration: 1. 1. 2024 - 31. 12. 2024
Evidence number:
Program: DoktoGranty
Project leader: Mgr. Rušinová Laura
Annotation: The aim of the project is to find out which acetylcholine receptors can potentially be produced in oocytes and preimplantation embryos. In the project, the expression of transcripts of all known subunits of mammalian nicotinic receptors and all types of muscarinic receptors will be investigated in a mouse model. The obtained transcriptomic data will enable further investigation of the biological function of these receptors in the earliest stages of embryogenesis and may also contribute to clarifying the mechanisms by which some adverse factors (nicotine, neonicotinoid insecticides) act on the developing oocyte and embryo.
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Duration: 1. 1. 2024 - 31. 12. 2024
Evidence number: APP0532
Program: DoktoGranty
Project leader: Mgr. Radič Rebecca
A new insight at isothiocyanates as substances interfering with the homeostasis of neoplastically transformed cells
Duration: 1. 1. 2021 - 31. 12. 2024
Evidence number: 2/0130/21
Program: VEGA
Project leader: RNDr. Imrichová Denisa, PhD.
SAS cosolvers: RNDr. Bertová Anna, PhD., prof. Ing. Breier Albert, DrSc., Ing. Kavcová Helena, Ing. Kontár Szilvia, PhD., RNDr. Kšiňanová Martina, PhD.
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Duration: 1. 1. 2021 - 31. 12. 2024
Evidence number: 1/0554/21
Program: VEGA
Project leader: prof. MVDr. Faix Štefan, DrSc.
Monitoring the interconnection of molecular events leading to the development of multidrug resistance in leukemic cells
Duration: 1. 1. 2021 - 31. 12. 2024
Evidence number: 2/0171/21
Program: VEGA
Project leader: Ing. Sulová Zdena, DrSc.
SAS cosolvers: Mgr. Cagala Martin, PhD., Ing. Janotka Ľuboš, PhD., Ing. Kadlečíková Karolína, Ing. Kyca Tomáš, PhD., Mgr. Pavlíková Lucia, PhD., Mgr. Šereš Mário, PhD., Ing. Šimoničová Kristína, PhD.
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Duration: 1. 1. 2024 - 31. 12. 2024
Evidence number: APP0534
Program: DoktoGranty
Project leader: Ing. Idunková Alžbeta
The role of protein-protein interactions in regulation of the cardiac ryanodine receptor
Duration: 1. 1. 2021 - 31. 12. 2024
Evidence number: 2/0018/21
Program: VEGA
Project leader: Mgr. Gaburjáková Jana, PhD.
SAS cosolvers: Mgr. Gaburjáková Marta, PhD., RNDr. Krejčíová Eva
Annotation: Ca2+ ions, essential for contraction of cardiomyocytes, are released from the sarcoplasmic reticulum (SR) via the cardiac ryanodine receptor (RYR2), an indispensable component of the excitation-contraction coupling machinery. Function of the RYR2 channel is modified by multiple associated proteins, located on both cytoplasmic and luminal RYR2 faces. The goal of this project is to investigate new aspects of protein-protein interactions involved in RYR2 regulation from the luminal side where calsequestrin (CSQ2) presumably senses and translates changes in luminal Ca2+ to the RYR2 channel. However, the RYR2 channel possesses also intrinsic luminal Ca2+ sensor within its first luminal loop. The physiological roles of such luminal sensors and their co-existence remain to be defined. We will examine what structural changes in CSQ2 induced by Ca2+ are communicated to the RYR2 channel and whether the regulation role of CSQ2 could be replaced by calreticulin, which is overexpressed in the SR in the absence of CSQ2.
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Duration: 1. 1. 2024 - 31. 12. 2024
Evidence number: APP0506
Program: DoktoGranty
Project leader: Mgr. Ďurišová Ivana
Iron intake and antibiotic resistance in food animal Enterobacterales.
Duration: 1. 1. 2021 - 31. 12. 2024
Evidence number: 2/0010/21
Program: VEGA
Project leader: RNDr. Bujňáková Dobroslava, PhD
SAS cosolvers: Alexiová Zuzana, Ing. Hamarová Ľudmila, PhD., MVDr. Karahutová Lívia, PhD., Prof., MVDr. Kmeť Vladimír, DrSc., MVDr. Kocúreková Tímea
Annotation: The main objective of the proposed project will be to obtain a new knowledge about the relationship betweenantibiotic resistance, virulence, ferric ions uptake and biofilm formation on model species of food animal bacteriai. e. Enterobacterales and Escherichia concerning to extraintestinal - ExPEC, avian pathogenic - APEC andverotoxigenic – VTEC Escherichia coli, Klebsiella, Enterobacter. Research will be focused on the most importantmechanisms of resistance: plasmid ampicillinases, cephalosporinases, carbapenemases, plasmid resistance tofluoroquinolones and resistance to colistin. Bacterial clonal relatedness and sequence type (ST) of selectedEscherichia coli isolates will be also determined. The achieved results will be applicable in bacteriologicaldiagnostic of resistance mechanisms by interpreting reading of minimal inhibitory concentration of antibiotic andin student education.

Finished

Kryofertilita - Cryopreservation of cattle gametes and embryos for gene banking
Duration: 1. 7. 2020 - 30. 6. 2024
Evidence number: APVV-19-0111
Program: APVV
Project leader: RNDr. Antalíková Jana, PhD.
SAS cosolvers: Ing. Horovská Ľubica, Ing. Jankovičová Jana, PhD., Ing. Michalková Katarína, PhD., Ing. Sečová Petra, PhD.
Annotation: Cryopreservation and subsequent long-term preservation of gametes from genetically significant individuals of different livestock breeds play an important role in solving the issue of preserving animal gene resources. The methods of freezing of oocytes and ovarian tissues must ensure their good quality and viability after thawing. In ourprevious studies, we tested the in vitro cryopreservation procedure of mature bovine oocytes, which proved to be more successful compared to freezing of ovarian fragments containing follicles with immature oocytes. However, due to the high variability of results after in vitro fertilization of thawed oocytes, this strategy requires furtheroptimization. The project will be focused on increasing the survival of oocytes after thawing and minimizing freezing damages to oocytes, as well as on promoting cell division and development of preimplantation embryos in vitro derived from frozen oocytes. In this concern, besides optimizing the cryopreservation regime, we plan to modify theculture conditions by using special additives to the culture media (antioxidants, growth factors, etc.). It is expected that optimization of the methods would ensure greater cryotolerance of bovine oocytes and in vitro produced embryos for gene bank preservation purposes.
Novel antidepressant therapy - long term consequencies on offspring
Duration: 1. 7. 2020 - 30. 6. 2024
Evidence number: APVV-19-0435
Program: APVV
Project leader: prof. RNDr. Lacinová Ľubica, DrSc.
SAS cosolvers: MMedSc Dremencov Eliyahu, DrSc, Ing. Dubiel Lucia, PhD., Mgr. Gaburjáková Jana, PhD., Mgr. Gaburjáková Marta, PhD., MUDr. Grinchii Daniil, PhD., Ing. Idunková Alžbeta, Mgr. Jurkovičová Tarabová Bohumila, PhD., Mgr. Tomko Matúš, PhD.
Omnipotence - Defense mechanisms of microbial and animal cells in reducing their sensitivity to plant defensive compounds
Duration: 1. 7. 2020 - 30. 6. 2024
Evidence number: APVV-19-0094
Program: APVV
Project leader: Ing. Sulová Zdena, DrSc.
SAS cosolvers: RNDr. Bertová Anna, PhD., RNDr. Boháčová Viera, CSc., Mgr. Cagala Martin, Mgr. Garaiová Martina, PhD., RNDr. Griač Peter, DrSc., Mgr. Holič Roman, PhD., RNDr. Imrichová Denisa, PhD., Ing. Janotka Ľuboš, PhD., Ing. Kavcová Helena, Ing. Kontár Szilvia, PhD., Ing. Kyca Tomáš, PhD., Mgr. Pavlíková Lucia, PhD., Mgr. Petrisková Lívia, Ing. Pokorná Lucia , PhD., Ing. Sulová Zdena, DrSc., Mgr. Šereš Mário, PhD., Ing. Šimoničová Kristína, PhD., Mgr. Valachovič Martin, PhD.
Annotation: Living organisms have developed during evolution different strategies for securing better position in the competition for vital sources. Biosynthesis of various biologically active substances enabled specific organisms to be more successful than others. Plant metabolites have important position among these substances. Many products of plantsecondary metabolism are known as effective pharmacological tools. A widespread use of these plant products can be predicted in various applications in veterinary and human medicine, food safety, etc. These applications willdepend on the development of knowledge in biosciences, to which the presented project aims to contribute. The ability to modify the structure of known substances of plant origin in the laboratory gives almost unlimited possibilities for the rational design of new biologically active structures. Therefore, we choose "OMNIPOTENCE" asthe acronym of our project. The project is aimed primarily on several plant products and their semisynthetic analogues as possible tools for modulation of proliferation and phenotypes of neoplastic and microbial cells. Living cells have developed several defensive strategies against toxic attacks mediated by different substances. The ability to develop such strategies may be considered as a basal characteristic that enables the cell to survive in the hostile environment. In addition to response specific for various organisms, general strategies have developedduring evolution that are functional in various types of living cells including mammalian neoplastically transformed cells, eukaryotic and prokaryotic microbial cells. The proposed project will focus on detailed analysis of the mechanisms how neoplastic mammalian and microbial cells respond to selected plant defensive substances andtheir semisynthetic derivatives.
KINSPL - Post-translational regulation of pre-mRNA splicing factors
Duration: 1. 7. 2021 - 30. 6. 2024
Evidence number: APVV-20-0141
Program: APVV
Project leader: Mgr. Bágeľová Poláková Silvia, PhD.
SAS cosolvers: Mgr. Bakošová Anetta, PhD., Mgr. Balážová Mária, PhD., Ing. Čipáková Ingrid, PhD., Mgr. Holič Roman, PhD., Mgr. Jurčík Ján, RNDr. Kretová Miroslava, PhD., RNDr. Osadská Michaela, PhD., Mgr. Piteľová Alexandra, Mgr. Selický Tomáš, PhD., Mgr. Valachovič Martin, PhD.
Annotation: Many splicing factors have been shown to be post translationally modified by phosphorylation, however, very little is known about the principles of this regulation. Additionally, linking protein kinases with functional consequencesfor the splicing factors they target is quite challenging. Recently, we performed systematic analysis of spliceosomalsubcomplexes of fission yeast S. pombe and identified novel phosphomodifications of splicing factors. Phenotypicanalysis of phospho-mimicking and phospho-null mutants of selected splicing factors revealed that their activitiesare robustly regulated by phosphorylation. Importantly, we identified several spliceosome-associated proteinkinases which are likely to regulate the spliceosome through phosphorylation of splicing factors.In this project, we will continue in our effort and will study the dynamics of spliceosome phosphorylation. We willestablish direct connections between splicing factors and the spliceosome-associated protein kinases. Affinitypurification followed by advanced mass spectrometry and ATP analog-sensitive mutants of spliceosomeassociatedprotein kinases will be employed to characterize the dynamics of spliceosome phosphorylation. We will also analyse in detail the splicing alterations induced in splicing phosphomutants using RNA-seq and qRT-PCRanalyses, and compare them with the alteration evoked after inhibition of spliceosome-associated protein kinases.This will allow us to identify specific phosphomodifications of splicing factors which are determinative for splicingtransitions and coordinated regulation of splicing.It is widely accepted that studying the post-translational regulation of splicing is crucial to get better insight into themechanisms regulating gene expression in normal and pathological states. Thus, understanding of the regulatorymechanisms of splicing factors will ultimately lead to approaches to correct or circumvent splicing-related diseasesat the molecular level.
LEBRE - Multidrug resistance of leukemia cells - Phenotype caused by interference of multimodal molecular reasons
Duration: 1. 7. 2020 - 30. 6. 2024
Evidence number: APVV-19-0093
Program: APVV
Project leader: Ing. Sulová Zdena, DrSc.
SAS cosolvers: RNDr. Bertová Anna, PhD., RNDr. Boháčová Viera, CSc., Mgr. Cagala Martin, RNDr. Imrichová Denisa, PhD., Ing. Janotka Ľuboš, PhD., Ing. Kavcová Helena, Ing. Kontár Szilvia, PhD., Ing. Kyca Tomáš, PhD., Mgr. Pavlíková Lucia, PhD., Mgr. Šereš Mário, PhD., Ing. Šimoničová Kristína, PhD.
Annotation: The multidrug resistance (MDR) of neoplastic cells represents a serious problem in the treatment of cancer. Tumor transformed cells could develop a wide range of defense mechanisms that enable them to escape from apoptosis induced by chemotherapy. In our project, we will focus on research concerning the development and particularlyidentification of mechanisms involved in resistance of leukemic cells. The most common molecular feature responsible for development of MDR in neoplastic cells represent expressions and transport activity of transporters belonging from the ABC gene family, and particularly the best-known member of this family ABCB1 protein alsoknown as P-glycoprotein (P-gp). Our findings in the previous period has shown that during development of multidrug resistance associated with P-gp overexpression several alterations of processes lead to cell death (such as: response to endoplasmic reticulum stress, deregulation of calcium dependent processes in the intracellularspace or induction and progression of programed cell death – apoptosis) could occurred. These alterations are associated with the remodeling of surface proteins and their ubiquitination and glycosylation. These changes, and probably many others, create a complex insight of the molecular changes responsible for the reduced response ofleukemia cells to the drugs induced apoptosis. In the current project we will focus to bring novel results important for understanding of the interplay of various molecular changes involved in development of multidrug resistance in leukemia cells. As a model we will use cell sublines obtained by adaption of parental leukemia cells to stressors of endoplasmic reticulum, proteasome inhibitors, hypomethylating agents and vincristine.