Development of Monoclonal antibodies of Rickettsiae and their employment in diagnosis assay
Vývoj monoklonálnych protilátok Rickettsiae a ich využitie v diagnostike
Program:	VEGA
Project leader:	Mgr. Quevedo Diaz Marco PhD.
Annotation:	Rickettsioses are zoonotic infections caused by members of the genus Rickettsia. Rickettsial illnesses share common clinical manifestations, such as fever, malaise, exanthema, the presence or absence of an inoculation eschar, and lymphadenopathy. The reported incidence of these diseases has increased during the previous decade in Europe. In our region, Mediterranean Spotted Fever and TIBOLA(caused by Rickettsia conorii and Rickettsia slovaca respectively) continue to be the most prevalence rickettsial diseases. Due to many similar symptoms with commonly occurring infections, its clinical diagnosis is very challenging. No rapid laboratory tests are available to diagnose rickettsial diseases early in the course of illness; serological assays still remain an indispensable tool in their diagnosis. In our previous work, we were able to detect new biomarkers for diagnosis of rickettsioses. The principal aim of this study is generate specific antibodies against biomarkers (eg. Lipopolysaccharide and proteins) for de
Duration:	1.1.2019 - 31.12.2022

New perspectives in the treatment of cardiovascular complications associated with COVID-19
Nové perspektívy v liečbe kardiovaskulárnych komplikácií spojených s COVID-19
Program:	SRDA
Project leader:	Ing. Zorad Štefan CSc.
Annotation:	Coronavirus disease 2019 (COVID-19), linked to severe acute respiratory syndrome induced by coronavirus-2 (SARS-CoV-2), was declared as a global pandemic. While respiratory failure is the major cause of mortality due to COVID-19, the great number of patients exhibit cardiovascular disorders. Understanding the underlying mechanisms of cardiovascular complications associated with COVID-19 is of the great importance to reach the effective therapy and to reduce mortality due to COVID-19. In this project we will imitate the inhibition of ACE2- mediated signalling induced by SARS-Cov-2 using highly specific ACE2 inhibitor MLN-4760. In this pharmacological model of COVID-19 in spontaneously hypertensive rats (SHR) we intend to examine the extend of MLN-4760-induced vascular damage as well as the mechanisms underlying the action of taxifoline and zofenapril, as perspective pharmacological tools for the treatment of cardiovascular complications associated with COVID-19. TX has been chosen as it was shown as promising drug-like substance inhibiting SARS-Cov-2 replication via inhibition of the main protease (Mpro). ZF is sulfhydryl-containing angiotensin converting enzyme (ACE) inhibitor spontaneously releasing hydrogen sulfide (H2S). Both substances provide several additional cardioprotective effects associated with elevated NO bioavailability and H2S release, respectively. These effects can improve PP-COVID 2020 Základný výskum PP-COVID-20-0043 Akronym: ACE2-TXZF 13.07.2020 14:53 Strana/Page: 2 function of the cardiovascular system via elevation of NO and H2S-mediated vasodilatation, inhibition of trombogenesis and induction of antioxidant and antiinflamatory action.
Duration:	16.9.2020 - 31.12.2021

Multidrug resistance of leukemia cells - Phenotype caused by interference of multimodal molecular reasons
Viaclieková rezistencia u leukemických buniek - fenotyp spôsobený interferenciou viacerých molekulárnych príčin
Program:	SRDA
Project leader:	Ing. Brtko Július DrSc.
Duration:	1.7.2020 - 30.5.2024

The analysis of bioactive substances associated with Murine herpesvirus with antiproliferative and immunomodulatory properties in vitro and in vivo
Analýza bioaktívnych látok asociovaných s Myším herpetickým vírusom s antiproliferatívnymi a imunomodulačnými vlastnosťami v podmienkach in vitro a in vivo
Program:	VEGA
Project leader:	RNDr. Labudová Martina PhD.
Duration:	1.1.2018 - 31.12.2021

Analysis of factors affecting a crop response to the potyvirus infection at the molecular and cellular level.
Analýza faktorov ovplyvňujúcich odpoveď plodiny na infekciu potyvírusmi na molekulárnej a bunkovej úrovni.
Program:	SRDA
Project leader:	Ing. Glasa Miroslav DrSc.
Annotation:	The Potyvirus genus includes a third of all known viruses infecting crops and wild-growing plant communities. In recent years, there have been many reports of epidemic outbreak cases caused by emerging viruses or by new divergent forms of already known viruses. The aim of the project is a comprehensive analysis of the plant-virus interactions at the molecular and cellular level with focus on potyviruses causing serious damage to major crops (vegetables, potatoes, oil plants). Metagenomic analysis using next generation sequencing (NGS) will allow an unbiased view on the plant virome. In addition to full-length characterization of genomes, identification of mixed infections and previously overlooked intra-isolate diversity, we will evaluate possible evolutionary factors potentially enhancing the competitiveness of potyviruses (genome recombinations, mutations). The obtained results will be used to develop and optimize detection tools enabling specific monitoring of the virus (ory its strains or forms, respectively) in subsequent epidemiological studies (host range, cultivar sensitivity, antagonism / synergism in complex infections ...). Using potyviral infectious clones and interspecies chimeric forms, we will analyze molecular factors of host specificity by monitoring changes in pathogenesis and host spectrum. Comparison of the proteomic profiles of healthy and infected plants with various degrees of pathogen sensitivity will allow a global view of the complex biological changes induced by a potyvirus infection. Understanding the mechanism of factors influencing the evolution of the virus and its virulence is essential for the adoption of effective preventive phytosanitary measures and the efficient control of potyvirus diseases.
Duration:	1.7.2019 - 30.6.2023

Analysis of the virome complexity and intra-species diversity from agricultural and wild plants in various agroecological contexts.
Analýza komplexnosti a vnútrodruhovej diverzity virómu poľnohospodárskych a divorastúcich druhov rastlín z rôznych agroekologických kontextov.
Program:	VEGA
Project leader:	Ing. Glasa Miroslav DrSc.
Annotation:	The recent introduction of new generation sequencing (NGS) into plant virus research has significantly altered the view on the complexity of plant viral infections while opening up new possibilities for study of plant virome. The project focuses on virome analysis using NGS, with samples coming from a variety of agroecological contexts potentially affecting the complexity of infections (perennial and annual agricultural species and wild plants). In addition to the potential identification of new viruses or highly divergent forms of known viruses, we will evaluate the genetic diversity of pathogens and the involved evolutionary mechanisms, as important factors for pathogen adaptation to the host. Genomic data will be used to analyze intraspecific molecular diversity and viral population polymorphism. Using variants-specific detection tools, the frequency and competitiveness of viral variants in mixed infections under natural and experimental conditions and their epidemiological consequences will be monitored.
Duration:	1.1.2020 - 31.12.2023

Anti-myeloma activity by composite realgar nanomaterials and its mechanism in vitro and in vivo
Anti-myelómová aktivita nových kompozitných nanomateriálov a ich mechanizmus účinku in vitro a in vivo
Program:	VEGA
Project leader:	RNDr. Jakubíková Jana PhD.
Annotation:	Myeloma resistance to therapy is a serious medical problem, and the identification of new drugs and treatments is still an ongoing task in overcoming intrinsic or treatment-induced primary resistance of tumor and/or tumor microenvironment. One promising approach is to use newly designed composite nanoparticles (NPs) prepared by nanosizing by high-energy milling and organic modification for better biocompatibility and targeted effects. The combination of new as well as conventional anti-myeloma drugs with targeted designed composite NPs efficiently link systemic chemotherapy and nanomedicine to achieve elimination of tumor mass. The proposed project develops long-term collaboration on material and oncology research to characterize cellular and molecular responses to the presence of new composite nanomaterials and to identify NPs with optimal anti-cancer activity.
Duration:	1.1.2020 - 31.12.2022

Antiviral therapy and vaccination as tools for lowering the course of influenza and bacterial co-infection.
Antivírusová terapia a vakcinácia ako nástroj na zmiernenie priebehu chrípkovej a bakteriálnej koinfekcie.
Program:	VEGA
Project leader:	RNDr. Varečková Eva DrSc.
Annotation:	Infuenza A virus (IAV) infections are often complicated by bacterial coinfection ending even fatally. Antiviral therapy is applied in praxis rarely and only in case bacterial superinfection is developed, antibiotics are used. However, after necrotic pneumonia starts on, antibiotic need not be effective in recovery from severe infection. Such cases were reported during the H1N1 pandemic in 2009. It is therefore reconsidered the need of early onset of antiviral therapy to lower the risk of severe course of coinfection. The aim of our project is to know the influence of antiviral application on complex immune response induced by IAV infection, especially on protective antibody induction. The second goal is to study the influence of antiviral therapy and IAV vaccination with new vaccines on the course of coinfection. The knowledge of mechanisms started during the IAV and bacterial coinfection could answer the question of substantiation of antiviral therapy in prevention from complications related to coinfection.
Duration:	1.1.2019 - 31.12.2022

Biological effects of nitrosopersulfide and reactive sulfur species on mitochondria
Biologické účinky nitrózopersulfidu a reaktívnych foriem síry na mitochondrie
Program:	VEGA
Project leader:	Mgr. Grman Marián PhD.
Annotation:	Hydrogen sulfide (H2S) and nitric oxide (NO) are endogenously produced gaseous signaling molecules with similar chemical and biological properties, which affect many physiological functions. Recent results showed that reactive sulfur species (RSS), oxidation products of H2S, and nitrosopersulfide (SSNO–), product of H2S-NO interaction, also play an important role in cellular signaling. In our proposed project we aim to study the effect of RSS and SSNO– on mitochondria as crucial cell energetic centre. We will focus on their effect on chloride channels of the inner mitochondrial membrane, mitochondrial transmembrane potential, as well on their interaction with cytochrome c oxidase, which is the main target of electron transport chain during the inhibition mediated by H2S and NO. Obtained results will contribute to better understanding of RSS and SSNO– role, the new signaling molecules, in redox regulation of mitochondria and whole cells and lead to development of new drugs with potential clinical application.
Duration:	1.1.2019 - 31.12.2022

Development of bioimmunotherapeutics inspired by viral tricks: TREATing despite the TRICKs
BIOTREAT - Vývoj bioimunoterapeutík inšpirovaný vírusovými trikmi: Liečenie aj napriek trikom
Program:	SRDA
Project leader:	Mgr. Nemčovičová Ivana PhD.
Annotation:	The immunotherapy is now one of the hottest areas in research, however, our aim is to work on immunotherapy that set out in novel direction – by tricking the body’s own defenses inspired by viral tricks into fighting the enemy within. Our main goal is to look at the molecules that cytomegalovirus uses to turn down the immune system to figure out how to develop a new biotherapeutic drug to treat both viral and autoimmune diseases. Within the project, we will investigate two important viral proteins (UL141 and UL144) that function on NK and T cells and how they act in both healthy and disease states. The aim is to produce a detailed picture of their molecular architecture and function and therefore to serve as a molecular-level blueprint for rationalized design of bioimmunotherapeutics and this will be tested by computational methods in parallel to in vitro biological testing on both normal and tumor cells. The determination of such factors regulating receptor and ligand expression on the cell surface and to identify a potentially inhibitable interaction between these cellular restriction factors and a viral antagonist will allow for a better understanding of the role of these viral proteins in immune responses and how these pathways can be manipulated for therapeutic intervention. This project is the logical continuation of our previous work and an existing joint collaborative initiative in dealing with development of bioimmunotherapeutics.
Duration:	1.7.2020 - 30.6.2024

Targeted inhibition of SARS-CoV-2 by a new generation RNA inhibitor
Cielená inhibícia SARS-CoV-2 pomocou RNA inhibítora novej generácie
Program:	SRDA
Project leader:	Mgr. Bábelová Andrea PhD.
Annotation:	The worldwide paralysis caused by the SARS-CoV-2 coronavirus pandemic has launched a global fight against this threat on several fronts. From a medical point of view, preventive measures and symptomatic treatment are so far the only tools to combat this virus. The absence of a specific therapeutic solution against SARS-CoV-2 thus represents a priority challenge for research and development of tailor-made antivirals for clinical practice. And all this ideally in the shortest possible time. The proposed ASCOVIDA project is an integral part of this call and has the ambition to bring a validated functional solution in the form of a SARS-CoV-2 RNA inhibitor within 15 months of the project duration. This solution is based on a patented method of nucleic acid inhibition, the therapeutic potential of which has been successfully validated for oncological diagnoses. The tested RNA inhibitor of an original structural design was spontaneously internalized and, after selective inhibition of causal RNA, induced cell death of tumor cells without any evident toxicity to healthy cells. Therapeutic strategies based on drug-RNA interference thus provide a rational and realistic assumption for the efficacy of analogous inhibitors towards RNA of viral origin in host cells. The design, synthesis and functional validation of an RNA inhibitor specifically designed for SARS-CoV-2 is thus the clearly defined scope of the ASCOVIDA project, which, if successfully validated, will bring a candidate antiviral agent for translation into clinical practice.
Duration:	16.9.2020 - 31.12.2021

New Antiviral Drugs: Design, Synthesis and Activity Evaluation of Specific Inhibitors of Viral Proteases of Coronavirus SARS-CoV-2
CoViDrugs - Nové antivirálne liečivá: Dizajn, syntéza a testovanie aktivity nových špecifických inhibítorov virálnych proteáz koronavírusu SARS-CoV-2
Program:	SRDA
Project leader:	Mgr. Nemčovičová Ivana PhD.
Annotation:	The pandemic of the new coronavirus SARS-CoV-2, which causes serious diseases of the respiratory tract (COVID-19), poses a long-term threat to the health of the population. Although intensive research into vaccines and antiviral drugs is underway worldwide, only one broad-spectrum antiviral drug, the prodrug remdesivir, has been approved for the treatment of COVID-19. Therefore, a key task worldwide is to find new specific antivirals against SARS-CoV-2. Our team, based on previous experience in designing new antiviral agents (e.g. against HIV- 1, HCV, Dengue, influenza A virus), began immediately after the COVID-19 outbreak intensive research into inhibitors effective against viral proteases - main protease Mpro and papain-like protease PLpro of SARS-CoV-2 virus, which are among the key targets for inhibition of viral replication. The previous results are followed in this project. Our team combines competencies of five experienced groups from universities (UCM, FaF and PriF UK) and Academy od Sciences (CHÚ SAS and VÚ CBMV SAS). The project strategy is based on an integrated approach. In the proposed project we focus on: • Computer-assisted design and optimization of new specific peptidomimetic α-ketoamides that inhibit the proteolytic activity of Mpro and of a series of bis-benzylidene cyclohexanones that inhibit the deubiquitination activity of PLpro of the coronavirus SARS-CoV-2. • Development of synthetic routes and synthesis of peptidomimetic α-ketoamides and bis- benzylidenecyclohexanones. • Testing of inhibition of enzymatic activity of both groups of substances on recombinantly prepared enzymes Mpro and PLpro and development of new methods for testing for inhibitory activity on viral enzymes. • Testing the antiviral activity of both groups of substances at the level of inhibition of human cell lines infected with SARS-CoV-2 virus. • Research into the interactions of new inhibitors with biological membranes and optimization of absorption in the respiratory tract
Duration:	16.9.2020 - 31.12.2021

Exercise in prevention & treatment of chemotherapy-related late toxicity in testicular germ cell cancer survivors: the role of skeletal muscle
Cvičenie v prevencii a liečbe neskorej toxicity chemoterapie u vyliečených onkologických pacientov: úloha kostrového svalstva
Program:	VEGA
Project leader:	Mgr. Ukropec Jozef DrSc.
Annotation:	Regular exercise is effective in prevention & treatment of chronic diseases. Exercise can reduce late toxicity of chemotherapy, commonly found in cancer survivors, which is yet to be translated into clinical practice. Mechanisms of exercise benefits in oncologic patients are far from being elucidated, and include increase in muscle mass, reduction of fat mass, systemic inflammation and cardiometabolic risk. Synchronization of exercise adaptive response is, to an extent, mediated by bioactive molecules released from muscle, with antiinflammatory & tumor-suppressing properties. Muscle satellite cells are a source of regeneration, muscle structural integrity & funcional capacity. Phenotypes of muscle cells, such as secretory profile, lipid & glucose metabolism, mirror clinical phenotypes of the donor. Importantly, muscle cells’ metabolism in vitro can be modulated by 8-12 week training in vivo. Epigenetic mechanisms regulating muscle & systemic metabolism in cancer survivors are not yet understood.
Duration:	1.1.2020 - 31.12.2023

Diagnostic and pharmacogenetic aspects of monogenic diabetes type MODY
Diagnostické a farmakogenetické aspekty monogénového diabetes mellitus typu MODY
Program:	VEGA
Project leader:	RNDr. Gašperíková Daniela DrSc.
Duration:	1.1.2018 - 31.12.2021

Diagnostic potential of body fluid fluorescent characteristics and extracellular microvesicles analyses in urogenital malignancies
Diagnostický potenciál monitorovania fluorescenčných charakteristík telových tekutín a analýzy extracelulárnych mikrovezikúl u nádorových ochorení urogenitálneho systému
Program:	VEGA
Project leader:	RNDr. Sedlák Ján DrSc.
Duration:	1.1.2018 - 31.12.2021

Diglycosidases in biocatalysis
Diglykozidázy v biokatalýze
Program:	VEGA
Project leader:	Mgr. Horváthová Eva PhD.
Duration:	1.1.2019 - 31.12.2022

Long-term strategic research of prevention, intervention and mechanisms of obesity and its comorbidities
Dlhodobý strategický výskum prevencie, intervencie a mechanizmov obezity a jej komorbidít
Program:
Project leader:	prof. RNDr. Pastoreková Silvia DrSc.
Duration:	1.9.2019 - 28.2.2023

Dominant mutations in Wolfram syndrome: different mechanism to the recessive ones?
Dominantné mutácie u Wolframovho syndrómu: potenciálne rozdielny mechanizmus účinku v porovnaní s recesívnymi mutáciami
Program:	VEGA
Project leader:	RNDr. Cagalinec Michal PhD.
Annotation:	Wolfram syndrome is a rare hereditary disorder caused by mutations in the Wolframin1 gene. Product of this gene, the Wolframin1 (WFS1) is located in the membrane of endoplasmic reticulum (ER). WFS1 is highly expressed in pancreas, brain and heart. Function of WFS1 involves regulation of ER stress and modulation in calcium homeostasis. Moreover it affects mitochondrial dynamics and ATP production in neurons. Although Wolfram syndrome is traditionally considered as recessive disorder, in our patients, we have identified two novel mutations of WFS1 resembling dominant behaviour. Therefore in this project we plan to evaluate, whether these novel mutations of are dominant and whether dominant and recessive mutations in the WFS1 gene act via different signalling pathways in the matter of ER stress, calcium metabolism and their impact to mitochondrial dynamics. These parameters will be tested in a model of human neuronal and cardiac cell lines to reveal unique mechanisms of WFS1 function in the brain and heart.
Duration:	1.1.2019 - 31.12.2022

Ecology of host specificity in vector-borne parasites
Ekológia hostiteľskej špecifickosti vektormi prenášaných parazitov
Program:	SRDA
Project leader:	Mgr. Špitalská Eva PhD.
Duration:	1.7.2017 - 30.6.2021

Cell-in-cell phenomena as microevolutionary processes in cancer progression: a role for hypoxia-induced carbonic anhydrase IX
Fenomény “bunka v bunke” ako mikroevolučné procesy v nádorovej progresii: úloha hypoxiou-indukovanej karbonickej anhydrázy IX
Program:	SRDA
Project leader:	prof. RNDr. Pastoreková Silvia DrSc.
Annotation:	Cell-in-cell phenomena refer to situations, in which tumor cells (“winner cells”) engulf one or more viable cells (“loser cells”) to gain nutrients in periods of starvation. Such cell-in-cell structures have been observed in human tumors for decades, but the underlying mechanisms and relevance to cancer progression has remained largely unexplored. Emerging view on molecular and functional aspects of cell-in-cell phenomena suggests their involvement in microevolutionary processes that occur in highly heterogeneous tumor tissues and lead to selection of aggressive tumor cells. Despite increasing interest in cell-in-cell phenomena, their understanding still remains fragmentary. In this project, we aim to elucidate the contribution of hypoxia and acidosis in tumor microenvironment to two cell-in-cell processes, namely cell cannibalism and entosis, with particular focus on carbonic anhydrase IX (CA IX), which plays a key role in pH regulation as an adaptive response of tumor cells to hypoxia and oncogenic metabolism. To achieve this aim, we intend to employ state-of-the-art approaches of molecular and cell biology and experimental oncology, and to use unique CA IX expertise and specific reagents developed by our team since our discovery of CA IX. According to our working hypothesis, CA IX participates in induction of cell-in-cell structures and is associated with “winner” phenotype enabling tumor cells to sustain starvation, survive microenvironmental stresses and gain aggressive properties. We also hypothesize that CA IX does so via participation in metabolic rewiring, morphological plasticity, intercellular signalling and protection of tumor cells from hypoxia and acidosis. Finally, we propose that hypoxia and acidosis are microenvironmental stimuli that trigger formation of cell-in-cell structures and thereby accelerate microevolution in tumor tissue. These hypotheses are supported by preliminary results and implicit evidences from our published and unpublished data.
Duration:	1.7.2020 - 30.6.2024

Functional analysis and production of bioactive subsatnces in insects and ticks
Funkčná analýza a produkcia bioaktívnych látok hmyzu a kliešťov
Program:	SRDA
Project leader:	RNDr. Koči Juraj PhD.
Annotation:	In this project we will use molecular, bioinformatics, biochemical a physiological techniques for description of expression patterns and functional characterization of membrane guanylate cyclases which serve as receptors for large neuropeptides of insects and ticks - eclosion hormone (EH) and ion transport peptides (ITP and ITPL). Various experiments using physiological, molecular and genetic approaches indicate that these neuropeptides are required for regulation of normal development, homeostasis, metabolism and reproduction, but mechanisms of their action are not known. Since peptides of EH and ITP/ITPL family elicit cGMP production in target cells, we assume that their receptors are guanylate cyclases. We plan to use model insects Bombyx mori and Drosophila melanogaster which are most suitable for physiological experiments and genetic manipulations. The knowledge obtained from these studies will be utilized for RNAi knock-down of these receptors to suppress development and reproduction of ticks (Ixodes ricinus and I. scapularis). These ticks are in Europe the most important vectors of numerous pathogens causing serious diseases in humans and domestic animals. In addition, we will examine expression and function of receptors for biogenic amines (dopamine and GABA) which are very important for modulation of physiological processes during blood feeding of ticks.
Duration:	1.7.2019 - 30.6.2023

Functional analysis of regulation of DEAH/RHA helicases
Funkčná analýza regulácie DEAH/RHA helikáz
Program:	VEGA
Project leader:	Ing. Čipáková Ingrid PhD.
Duration:	1.1.2019 - 31.12.2022

Physiological relevance of medical and pharmaceutical sciences.
Fyziologický význam vnútrobunkového H2S v nádorových bunkách.
Program:	VEGA
Project leader:	RNDr. Hudecová Soňa CSc.
Duration:	1.1.2019 - 31.12.2021

Glycoprofiling of proteins present in serum and exosomes for early prostate cancer diagnostics
Glykoprofilácia proteínov prítomných v sére a v exozómoch pre včasnú diagnostiku rakoviny prostaty
Program:	Other projects
Project leader:	RNDr. Gábelová Alena CSc.
Annotation:	In this project we would like to identify novel glycan-based prostate cancer (PCa) biomarkers based on specific glycoprofiling of selected proteins either present in serum or in exosomes. We will integrate various assay protocols for such glycoprofiling using lectin-based ELISA, magnetic ELISA, antibody-lectin microarrays, electrochemistry, Surface Plasmon Resonance (SPR) and LFA (Lateral Flow Assays, pregnancy-like tests). The innovation of the project proposal can be summarized as follows: • Specific glycoprofiling of zinc -glycoprotein (ZAG) and prostatic acid phosphatase (PAP) present in the serum as potential PCa biomarkers; • Use of exosomes as a rich source of five glycoproteins to be glycoprofiled by lectins; • Application of innovative assay strategies with various assay formats; glycoproteins/exosomes will be affinity enriched by magnetic beads and the whole complex without any glycoprotein/exosome released will be incubated with lectin modified interface; • Use of LFA for glycoprofiling of proteins, which has not been used in the analysis of real samples.
Duration:	1.12.2019 - 30.12.2022

Impact of selected metal nanoparticles on steroidogenesis: comparison of in vitro cell models
Hodnotenie účinkov vybraných kovových nanočastíc na steroidogenézu: porovnanie in vitro bunkových modelov
Program:	VEGA
Project leader:	Mgr. Scsuková Soňa CSc.
Annotation:	Nanoproducts are becoming widely used in all aspects of life. Different types of NPs are often used in everyday products, such as cosmetics and foods. In medicine, nanoparticles (NPs) can be used as nanoscopic drug carriers and for nanoimaging technologies. Unique physicochemical properties of NPs (size, shape, polarity) may allow for their passage through biological barriers and thus, to have easier access to the organs and tissues in the body. NPs have been reported to induce reproductive toxicity, but the molecular mechanisms remain unclear. Reproductive physiology involves a series of complex physiological processes, including synthesis of steroid hormones that are sensitive to chemical contaminants. The present project will be focused on evaluation of impact of selected metal NPs with different physicochemical properties on steroidogenesis by considering gonadal and adrenal cells as vitro model systems. The obtained results provide new knowledge to guide safe and sustainable development of new NPs.
Duration:	1.1.2020 - 31.12.2022

Identification and validation of biomarkers and underlying molecular pathways of late toxicity of curative treatment in testicular germ cell tumors
Identifikácia a validácia biomarkerov a zodpovedných molekulárnych dráh neskorej toxicity kuratívnej liečby u germinatívnych nádorov testis
Program:	SRDA
Project leader:	doc. MUDr. Ukropcová Barbara PhD.
Annotation:	Testicular germ cell tumors (GCTs) are a unique malignancy with a long-term cure rate > 95%. The implementation of multi-modality treatment with cisplatin-based chemotherapy, radiotherapy and surgery have rendered GCTs as model for cancer cure. Growing population of GCT survivors can suffer from late toxicity of treatment, ultimately leading to lower quality of life, increasing long-term morbidity and early mortality. Among the known late toxic sequelae are secondary malignancies, cardiovascular toxicity, neurotoxicity, nephrotoxicity, pulmonary toxicity, hypogonadism, infertility, cognitive dysfunction, sexual function impairment and decline in quality of life. Proposed project aims to further develop ongoing programme of late toxicity research in National Cancer Institute in Slovakia. The project will focus on longitudinal assessment of distinct types of late toxicities and identify biomarkers and underlying molecular mechanisms. Two interventional randomized studies will be conducted to assess the effects of endurance and strength training. This project is the first state-of-the-art approach to implement comprehensive joined clinical and translational research with an attempt to identify and further analyse late toxicity of anti-cancer treatment also integrating the programme for prevention. The project is also considered to be a pilot comprehensive programme for survivorship initiatives and research applicable among other cancer types.
Duration:	1.7.2020 - 30.6.2024

Identification and validation of signalling pathways associated with circulating tumor cells in breast cancer
Identifikácia a validácia signálnych dráh asociovaných s cirkulujúcimi nádorovými bunkami pri karcinóme prsníka.
Program:	SRDA
Project leader:	Mgr. Miklíková Svetlana PhD.
Annotation:	Circulating tumor cells (CTC) are indepent prognostic factor in primary as well as in metastatic breast cancer. CTC are heterogenous population of tumor cells and play crucial role in metastatic cascade and tumor progression in process termed self-seeding. Presence of CTC in peripheral blood is a surrogate marker of tumor metastatic ability. Identification of signalling pathways associated with presense of CTC in peripheral blood could help to identifify new therapeutic targets in breast cancer. This project is aimed to identify biomarkers and subsequently signalling pathways in primary tumor associated with different subsets of CTC using using highthroughput technologies of genomics and biostatistcs through translational research involving the analysis of biological material from patients followed by their prospective validation.
Duration:	1.7.2017 - 30.6.2021

Identification of biomarkers of resistance to cisplatin-based chemotherapy in urogenital cancer
Identifikácia biomarkerov rezistencie na chemoterapiu cisplatinou pri nádoroch urogenitálneho traktu
Program:	VEGA
Project leader:	Mgr. Chovanec Miroslav PhD.
Annotation:	Testicular germ cell tumors (TGCT) affect young and bladder tumors (TCC) older men. Both cancers are curable with cisplatin (CDDP), but after first-line therapy, resistance to this drug may develop. Disease relapse can be associated with DNA repair and we assume that patients who relapse may have a more effective repair of CDDP-induced DNA damage due to different expression of DNA repair factors at both the mRNA and protein levels, as well as due to their post transcriptional and -translational regulation. Using TGCT and TCC cell lines displaying different CDDP sensitivity levels, we will identify mRNAs and miRNAs associated with resistance to this drug. We will also reveal the role of alternative mRNA splicing and phosphorylation in regulation of selected DNA repair factors. Finally, we will determine the extent of endogenous DNA damage in TCC and by correlating the obtained results with clinical data we will identify biomarkers of CDDP resistance. Selected biomarkers will be validated in clinical material.
Duration:	1.1.2019 - 31.12.2022

Identification of chemoresistant cell populations with metastatic potential in colorectal carcinoma
Identifikácia chemorezistenntých bunkových populácií s metastatickým potenciálom u kolorektálneho karcinómu
Program:	VEGA
Project leader:	RNDr. Matúšková Miroslava PhD.
Annotation:	Colorectal cancer (CRC) belongs to leading causes of cancer-related mortality worldwide as well in Slovak Republic. Metastases occur in more than half of the patients suffering from this disease, and they represent the key obstacle to the effective treatment of CRC. The majority of patients can not be cured. It is obvious that population of tumour cells which is not eliminated by chemotherapy consists of subpopulations which are capable to induce metastases. Based on published data as well as on our research it is evident that functional link between chemoresistance and metastatic process does exist. We aim to define the set of markers typical for chemoresistant cells with metastatic potential on the model of CRC and contribute to identification of characteristics typical for metastasis-initiating cells. The implementation of project will help to solve actual clinically-relevant issues associated with patients suffering from metastatic disease.
Duration:	1.1.2019 - 31.12.2022

Identification of molecular-genetic determinants of apocrine secretion
Identifikácia molekulárno-genetických determinantov apokrinnej sekrécie
Program:	SRDA
Project leader:	RNDr. Farkaš Robert CSc.
Annotation:	In contrast to classic and intensely studied exocytosis (merocrine secretion) the key components of which are well known, the molecular and genetic determinants of unconventional type of secretion such as apocrine and holocrine secretion remain enigmatic. When studying hormonally regulated programmed cell death in Drosophila salivary glands we have disclosed the process of apocrine seceretion which takes place shortly prior to execution phase of apoptosis. Using molecular and genetic tools available in Drosophila model organism we propose here to identify novel genes associated with this process, as well as to proteins that are components of apocrine secretion. With regard to the evolutionary conservation of numerous signaling pathways between fly and humans we anticipate that uncovering of these determinants in Drosophila may be useful also in sheding light on some pathologies that are associated with apocrine secretory dysfunction.
Duration:	1.7.2017 - 30.6.2021

Identification of the protein markers activated in the process of induction of the ischemic tolerance
Identifikácia proteinových markerov aktivovaných v procese navodenia ischemickej tolerancie
Program:	VEGA
Project leader:	RNDr. Mucha Rastislav PhD.
Duration:	1.1.2020 - 31.12.2022

Identification of psychological and somatic markers in relation to vulnerability to stress and analysis of the effectiveness of psychological interventions
Identifikácia psychických a somatických markerov v súvislosti s vulnerabilitou na stres a analýza efektivity psychologických intervencií
Program:	SRDA
Project leader:	prof. PharmDr. Ježová Daniela DrSc.
Annotation:	The project is aimed to establish the most comprehensive model of stress vulnerability based on a broad analysis of all relevant psychological along with somatic stress indicators and to identify maladaptive stress reactivity that is manifested by alostatic overload in the form of hyper-reactivity or hypo-reactivity to stress stimuli. On of the goal is to reveal optimal assessment of the cumulative risk of alostatic overload by evaluating biomarkers (cardiovascular, neuroendocrine, metabolic, inflammatory) and psychological parameters (emotional,personal, cognitive). Research is oriented toward subjects with increased stress vulnerability, both in the healthy population and in risk somatic states, with perspective of deep understanding of individual processes in the context of a changed stress response. The focus of the project is given on complexity and integration of knowledge to establish a stress-vulnerability model. The original benefit of the project is the creation of a precise group stress task, examination of sleep quality through ECG monitoring, or the development of new methods of hormone analysis in hair and saliva for detection a chronic stress. Besides the interdisciplinary approach to this issue, the main advantage of the project is a long-term experience in stress research under experimental as well as natural conditions of normal proband life. The aim is to analyze the effectiveness of different types of psychological interventions focused at reducing stress and better coping with stress (HRV biofeedback, autogenous training) and to assess the possibilities of their application in terms of understanding individual relationships within the stress vulnerability model.
Duration:	1.8.2018 - 31.7.2022

Integrative strategy in the development of personalized medicine of selected malignant cancer diseases and its effect on the quality of life
Integratívna stratégia v rozvoji personalizovanej medicíny vybraných zhubných nádorových ochorení a jej vplyv na kvalitu života
Program:
Project leader:	Mgr. Chovanec Miroslav PhD.
Duration:	1.9.2019 - 30.6.2023

Intelligent monitoring of wastewater in order to create a system of early warning of the population of the Slovak Republic against the spread of COVID-19
Inteligentné monitorovanie odpadových vôd za účelom vytvorenia systému včasného varovania populácie SR pred šírením ochorenia COVID-19
Program:	SRDA
Project leader:	MVDr. Kopáček Juraj DrSc.
Annotation:	Early detection of COVID-19 outbreaks is crucial for the prevention of uncontrolled spreading of the disease. Almost 50% of COVID-19 positive cases suffer from diarrhea and in targeted studies viral RNA was detected in feces of all SARS-CoV-2 positive patients. Thus, one of the most promising approaches to monitor the dynamics of the virus in the population is the analysis of sewage water. This represents a complex and challenging matrix for pre-analytical preparation of samples. Various filtration, centrifugation and extraction methods are being used before the samples can be analyzed for the presence of viral RNA. One of the aims of this project will be to optimize the protocol for the pre-analytical sewage water preparation, but also to test available analytical methods relying on PCR, isothermal amplification or CRISPR regarding their resistance to impurities from the sewage water. The main aim of the project is to develop and test an electrochemical immunobiosensor and/or aptasensor for monitoring of SARS-CoV-2 in sewage water from health care institutes, nursing homes, but also whole cities to quickly and automatically recognize potential outbreaks of the infection. Last but not least, an important part of the project will be to develop and test effervescent tablets based on the oxidizing agent – ferrate(VI) and boron doped diamond electrodes in order to decontaminate the sewage water with detected SARS-CoV-2. Combining the efforts of experts in engineering, virology and biophysics, this interdisciplinary project has the potential to help in the fight against SARS-CoV-2 in Slovakia.
Duration:	16.9.2020 - 31.12.2021

Host cell interaction with Coxiella burnetii: identification and utilization of novel therapeutic and diagnostic targets
Interakcia hostiteľských buniek s Coxiella burnetii: identifikácia a využitie nových terapeutických a diagnostických cieľov
Program:	SRDA
Project leader:	Ing. Škultéty Ľudovít DrSc.
Annotation:	Coxiella burnetii is an intracellular bacterial pathogen causing human infections of clinical and public health relevance. As many other bacterial pathogens, Coxiella uses specialized secretion systems to manipulate eukaryotic host cells by injection of effectors (bacterial virulence proteins and small molecules). However, current knowledge about how these pathogens establish infection is limited. The central research commitment of this project is the characterization of the functions of effector proteins from Coxiella burnetii. The project’s specific objectives include: 1) the description of the host cell signaling pathways targeted by effectors (proteins and small molecules) of Coxiella burnetii; 2) the characterization of the molecular and cellular mode of action of the effectors, and 3) a putative correlation between the mode of action of the effectors to their sequence variability and expression amongst different strains. The anticipated results may lead to the discovery of novel therapeutic approaches-drug targets- and could help in the design of vaccines and novel diagnostics. In particular, the host signaling pathways altered by one (or more) effector(s) will be promising candidates as novel therapeutic targets. Furthermore, the knowledge that will be gained could also lead to the identification of inhibitors targeting the pathogen’s effectors directly and help to design specifically drugs that can block the secretion system of the pathogen.
Duration:	1.7.2020 - 30.6.2024

Isolation, identification and characterization of transforming growth factor-beta 1 binding molecule(s) in tick salivary gland extracts.
Izolácia, identifikácia a charakterizácia transformujúci rastový faktor-beta 1 viažúcej molekuly v extraktoch slinných žliaz kliešťov.
Program:	VEGA
Project leader:	Mgr. Bartíková Pavlína PhD.
Annotation:	The transforming growth factor-beta 1 (TGF-b1) and its signaling pathway play a pivotal role in coordinating almost every aspect of normal tissue repair and homeostasis. The perturbation of TGF-b1 signaling is linked to autoimmunity, inflammation and cancer. The discovery of pro-oncogenic properties of TGF-b1 stimulated development of TGF-b1 signaling inhibitors as therapeutic strategy for combating cancer. Tick saliva contains an extraordinary array of biologically active molecules disarming host hemostatic, inflammatory and immune reactions; some of them with promising therapeutic potential. Considering this possibility and according to our discovery of tick salivary gland compounds ability to bind TGF-b1, we focus on isolation, identification and characterization of TGF-b1 binding molecule(s) from different tick species. Given the pleiotropic effects of TGF-b1, ticks and their molecular armaments may provide valuable tools and insights into aberrant wound repair and disorders.
Duration:	1.1.2019 - 31.12.2022

Is HIF-1a a master regulator of DNA repiar capacity and chemotherapy response in testicular germ cell tumors?
Je HIF-1a hlavný regulátor DNA reparačnej kapacity a odpovede na chemoterapiu v nádoroch semenníkov z germinatívnych buniek?
Program:	SRDA
Project leader:	RNDr. Jurkovičová Dana PhD.
Annotation:	Testicular germ cell tumors (TGCT) are highly curable malignity with cisplatin (CDDP) first line chemotherapy, gaining excellent response rates even in advanced metastatic stages. However, approximately 20-30% of patients do not respond to this treatment or relapse. These patients are predominantly young men and have a very poor prognosis. Early detection of CDDP resistance in these patients may be essential for the immediate initiation of more effective treatments that eliminate exposure of the patient to unnecessary CDDP cytotoxicity without therapeutic effect. Binding of CDDP to DNA and DNA damage are the major toxic and therapeutic effects of this treatment. CDDP generated DNA adducts can lead the cell to apoptosis and eliminate it, or be repaired by various DNA repair mechanisms, particularly homologous recombination (HR) and nucleotide excision repair (NER), which, by increased repair capacity, can critically contribute to CDDP resistance. In this project we will focus on the identification and characterization of molecular mechanisms responsible for modulating the efficiency of DNA repair by HR and NER and their role in chemoresistance, namely the regulatory role of hypoxia by hypoxia inducible factor (HIF, typical for solid tumors) and epigenetic regulation of DNA repair genes by miRNA and promoter methylation. Such modulation of repair capacity may explain the different response of TGCT to CDDP. We will attempt to answer the question whether HIF-1a can be the master regulator of this answer. Our intention is to identify early biomarkers of CDDP responses that would enable stratification of the TGCT patients prior to initiation of therapy or predict patients' sensitivity to other therapeutics, e.g. PARPi. The project outputs have the potential for transfer to clinical practice.
Duration:	1.7.2020 - 30.6.2023

Is hypoxia a master modulator of DNA repair capacity and mitochondrial dynamics in chemotherapy response in urogenital malignancies?
Je hypoxia kľúčovým modulátorom DNA reparačnej kapacity a metabolizmu mitochondrií v odpovedi testikulárneho karcinómu na chemoterapiu?
Program:	VEGA
Project leader:	RNDr. Jurkovičová Dana PhD.
Annotation:	Testicular germ cell tumors (TGCT) are cisplatin (CDDP) well treatable malignancy, with excellent response even in advanced metastatic stages. 20-30% of patients do not respond, relaps, and have a poor prognosis due to CDDP resistance. Several mechanisms are responsible for tumor cell resistance, leading the tumor cell to survive and avoid apoptosis. In the proposed project we will focus on: 1) DNA repair mechanisms contributing to the resistance increased capacity of DNA damage repair and 2) metabolism of mitochondria (dynamics, mitophagy) whose changes are critical for the cell response to induction of cell death. In the resistance of TGCT and other solid tumors, hypoxia and associated epigenetic modulation (by miRNA and methylation) are believed to be the key regulators. On TGCT cell lines we will focus on DNA damage and repair and selected mitochondrial proteins, and we will try to identify signaling pathways where HIF-1α and miRNA are the major regulators of these changes. Our aim is to identify and validate early molecular markers informing about CDDP resistance of TGCT patients before treatment initiation.
Duration:	1.1.2021 - 31.12.2024

Carbonic anhydrase IX: one of the key components of exosomes secreted from cancer cells
Karbonická anhydráza IX: jeden z kľúčových komponentov exozómov sekretovaných z nádorových buniek
Program:	VEGA
Project leader:	RNDr. Zaťovičová Miriam CSc.
Annotation:	Knowledge of the cellular processes that govern exosome biology is essential to shed light on the physiological and pathological functions of these vesicles, as well as for clinical applications. Current evidence suggests that exosomes participate in many key tumor-promoting processes. The subject of the proposed project is the exosome-located, tumor-associated protein carbonic anhydrase IX (CA IX), and implication of this enzyme’s extracellular form in many processes, such as its role in the tumor microenvironment, cancer metastasis, and in cancer immunity. We will use not only the latest in vitro cell biology methods in the project, including real-time cell parameter measurements but also in vivo experiments. Results of this project are expected to extend our knowledge on function of CA IX located in exosomes as an important cancer cell messenger, as well as a potential clinical biomarker.
Duration:	1.1.2020 - 31.12.2023

Clinical evaluation of prognostic and predictive value of tissue and serum Carbonic Anhydrase IX in breast cancer
Klinická evaluácia prognostickej a prediktívnej hodnoty tkanivovej a sérovej karbonickej anhydrázy IX v karcinómoch prsníka
Program:	Other projects
Project leader:	RNDr. Režuchová Ingeborg PhD.
Annotation:	Intratumoral hypoxia has clinically serious consequences, since cell adaptation to hypoxia increases resistance to anticancer drugs, radiotherapy, and leads to the expansion of cells with a more aggressive phenotype and to increasing tumor metastatic potential. Carbonic Anhydrase IX (CAIX) is a transmembrane protein whose expression is induced by HIF-1α transcription factor during hypoxia. CAIX is currently considered as an independent marker of poor prognosis, overall survival, and marker for assessing the risk of distant metastasis. The project aim is to define predictive and prognostic value of tissue-associated CAIX (tCAIX) and soluble CAIX (sCAIX) in breast cancer (CaMa) patients. We will analyze the presence of tCA IX in biopsy specimens obtained pre-operative during early diagnosis, in tumor tissue and/or sentinel node obtained during surgery. We will supplement this examination by monitoring sCAIX levels in patients' plasma before and during treatment, and follow-up care. sCAIX will be quantitated using a new ELISA.
Duration:	1.11.2019 - 31.12.2021

Comprehensive innovative diagnostics and personalized treatment of diabetes mellitus in children
Komplexná inovatívna diagnostika a personalizovaná liečba diabetes mellitus u detí
Program:	Other projects
Project leader:	RNDr. Gašperíková Daniela DrSc.
Annotation:	Type 1 diabetes accounts for more than 90% of diabetes mellitus (DM) in children, which greatly affects diagnosis because most cases are considered as type 1 diabetes. However, other (hereditary) types of diabetes, such as neonatal diabetes, MODY and various syndrome forms of DM, also manifest in children. Moreover, Type 1 diabetes is no longer considered to be a homogeneous disease. Precise identification of the DM type is needed for effective personalized treatment of the patients. While the distinction between diabetes types has been problematic in the past, innovative diagnostic methods are now available that allow us to accurately classify DM. The aim of our project is to develop a comprehensive innovative diagnosis of DM using molecular genetic methods and in clinical practice to apply this procedure to children monitored in DDC SR and to apply personalized management based on the principles of pharmacogenetics. At the same time, a biobank of children with DM will be built in order to respond more flexibly to the latest trends in diagnostics and treatment.
Duration:	1.10.2019 - 31.3.2022

The yeast Saccharomyces cerevisiae as a model to study the repair of clinically relevant DNA damage
Kvasinka Saccharomyces cerevisiae ako model pre štúdium mechanizmov opravy klinicky významných poškodení DNA
Program:	VEGA
Project leader:	RNDr. Goffa Eduard PhD.
Annotation:	This project aims to further characterize two clinically relevant DNA repair pathways in S. cerevisiae: non-homologous end-joining (NHEJ) and interstrand crosslink (ICL) repair. We will study the impact of SUMOylation of the ligation complex components Dnl4/Lif1/Nej1, mainly the Nej1 protein, on NHEJ. As the substitution K181R significantly decreases Nej1 SUMOylation in vitro, we will inquire whether it happens also in vivo and whether K181R impacts NHEJ efficiency. This effect could be caused by changes in ligation complex interactions with other NHEJ proteins, as well as changes in oligomerization of Nej1 itself. Next, we will focus on ICL repair specific for the S-phase of the cell cycle. We found out that the nuclease Rad1/Rad10 is partially involved in ICL repair in the S-phase even without the presence of the accessory protein Rad14, the major component of the nucleotide excision repair (NER). Our aim is to clarify the role of Rad1 in NER-independent ICL repair specific for the S-phase.
Duration:	1.1.2020 - 31.12.2023

Markers overlapping chemoresistance and metastatic potential in colorectal cancer - alhedyde dehydrogenase and its clinical relevance
Markery prekrývajúce chemorezistenciu a metastázovanie kolorektálneho karcinómu - úloha aldehyddehydrogenázy a jej klinická relevancia
Program:	Other projects
Project leader:	RNDr. Matúšková Miroslava PhD.
Annotation:	Metastases occur in more than half of the patients suffering from colorectal cancer (CRC). Their prognosis is unfavourable. Acquired chemoresistance is significant obstacle in treatment of patients with metastases. There is an increasing number of evidence that there is a functional overlap between chemoresistance and metastatic dissemination. The mechanisms of this phenomenon are not fully understood in CRC. We demonstrated significantly increased activity of aldehyde dehydrogenases (ALDH), particularly the 1A3 isoform on chemoresistant-spontaneously metastatic cell line. Transient molecular silencing of ALDH1A3 led to partial response to chemotherapy. We aim to verify a hypothesis that ALDH1A3 or other ALDH1 isoforms are common marker for chemoresistance and invasive phenotype in CRC, and knockout of ALDH1, or inhibition of associated signalling pathways, decreases the aggressive phenotype. The clinical relevance we confirm on organoids and patient-derived xenografts as well as by retrospective analysis of clinical material archived in biobank of National Cancer Institute.
Duration:	1.11.2019 - 31.12.2022

Mechanism of the mesenchymal stromal cell-induced tolerance to antitumor treatment and targeted therapeutic intervention in the breast cancer cells
Mechanizmus tolerancie indukovanej mezenchýmovými stromálnymi bunkami voči protinádorovej liečbe a cielená terapeutická intervencia v nádorových bunkách karcinómu prsníka
Program:	SRDA
Project leader:	Mgr. Miklíková Svetlana PhD.
Annotation:	Chemoresistance to conventional cytotoxic drugs used in breast cancer patients results in disease relapse, progression and dissemination. There are many intrinsic mechanisms in breast cancer cells contributing to refractoriness to chemotherapeutic agents. Tumor microenvironment surrounding the tumor cells, which is composed of many types of non-malignant cells and extracellular proteins, significantly affects drug responses by soluble-factor mediated and cell adhesion-mediated drug resistance. The interactions between the tumor cells and TME blunt the cytotoxic effect of genotoxic drugs thus substantially negatively affecting treatment efficiency. Mesenchymal stromal cells as one of the TME components represent relatively resistant cell population actively recruited and engrafted in the TME. The exposure to chemotherapeutic drug alters their phenotype thus substantially affecting tumor cell behavior. The project is focused on unraveling the molecular mechanism by which MSC blunt the response to chemotherapeutic agents and induce tolerance in otherwise intrinsically sensitive tumor cells. The project is focused on unraveling the point of therapeutic intervention to abrogate this MSC-mediated tolerance.
Duration:	1.7.2017 - 30.6.2021

Mechanisms of skeletal muscle adaptation to regular exercise in patients with chronic metabolic and inflammatory disease
Mechanizmy adaptácie kostrového svalu pacientov s chronickým metabolickým a zápalovým ochorením na pravidelné cvičenie
Program:	VEGA
Project leader:	RNDr. Novotová Marta CSc.
Annotation:	Low physical fitness is associated with impaired muscle functional parameters and high risk of chronic metabolic disease. In patients with idiopathic inflammatory myopathy, skeletal muscle function deteriorates also because of systemic inflammatory process, but it often persists even after suppression of inflammation. Regular exercise positively affects energy metabolism and muscle functional state in healthy individuals as well as in patients with metabolic disease or myopathy. Aim of this project is to identify structural, functional and molecular determinants of beneficial effects of exercise on mitochondrial respiration, metabolic substrate preference, myocyte ultrastructure and contractile function. Skeletal muscle biopsy & differentiated muscle cells obtained from metabolically well-characterized patients before/after the exercise intervention will be used. This knowledge is a key to our efforts to tackle the basic pathophysiological determinants of idiopathic inflammatory myopathy.
Duration:	1.1.2019 - 31.12.2022

Mechanisms of impact of low intensity electromagnetic radiation on course of cancer disease
Mechanizmy účinkov nízkoúrovňového elektromagnetického žiarenia na priebeh onkologických ochorení
Program:	VEGA
Project leader:	doc. Ing. Beliaev Igor DrSc.
Annotation:	Based on available models for magnetoreception and screening effective parameters of extremely low frequency (ELF) electromagnetic field (EMF) the effects of selected EMF on normal and cancer cells from most frequent and aggressive tumors and leukemic cells will be studied. The impact of EMF on inhibition of cancer cell growth will be analyzed in cells exposed to EMF alone and in combination with ionizing radiation that is widely used in treatment of cancer disease. Response of human cells to most frequent radiofrequency (RF) signals of mobile communication will also be analyzed. This analysis will be focused on stem cells, which represent a key target for origination of leukemia/tumors. The endpoints relevant for assessment of cancer risks and DNA damage response will be followed using state-of-the -art techniques. The obtained data will be correlated with cancer risks based on models for known carcinogens such as ionizing radiation.
Duration:	1.1.2018 - 31.12.2021

Metagenomic approach for the identification and characterization of viral diseases in selected medicinal plant species
Metagenomický prístup identifikácie a charakterizácie vírusových ochorení pri vybratých druhoch liečivých rastlín
Program:	SRDA
Project leader:	Ing. Glasa Miroslav DrSc.
Annotation:	Plants from the Papaveraceae and Solanaceae family are valued for their high content of secondary metabolites used in food and pharmaceutical industry. They belong not only to cultivated crops but they are also integral part of agroecological interface as well as wild plant communities representing important and poorly studied reservoir of viral pathogens. The project focuses on the identification and characterization of viral pathogens infecting these plants using highly progressive method of next generation sequencing (NGS), which allows an unbiased, highly parallel analysis of the complete virome directly in primary host plants. Detailed molecular analysis of virome will bring genuine data about the structure and diversity of viral populations spread on the evaluated plant species, including emerging or previously not classified viral species and will also contribute to the knowledge of the factors affecting their dissemination. Based on the obtained partial and complete genomic data, molecular detection methods will be developed to be subsequently applied in the study of etiology and epidemiology of the most widespread viruses. An important objective will also be a study of the effect of viral infection on alkaloid production in model plants by studying the expression of genes encoding selected enzymes in the alkaloid pathway.
Duration:	1.10.2017 - 30.6.2021

TArgetiNg Dna mEthylation by epigenetic editing and its implementation into personalised diagnostics and therapy of uveal Melanoma
Metylácia DNA ako cieľ epigenetického editovania a jej využitie pri personalizácii diagnostiky a terapie u melanómu uvey
Program:	SRDA
Project leader:	Mgr. Smolková Božena PhD.
Annotation:	Uveal melanoma (UM) is the most frequent intraocular tumour in adults, with metastatic dissemination to the liver or lungs in nearly half of the cases. At present there are no effective therapies for metastatic UM, and most patients survive less than 12 months after diagnosis of metastases. Recently published integrated analysis focused on identification of prognostic markers in UM identified four molecular subtypes of UM tumours, characterized by different metastatic risk. Beside divergent genomic aberrations and somatic copy number changes, DNA methylation profiles separated better-prognosis disomy 3 UM into low or intermediate risk, while poor-prognosis UM were characterized by distinct global DNA methylation pattern. In contrast with genetic factors, epigenetic inactivation of gene expression is reversible mechanism and its understanding promises to be amenable to treatment. The aim of this study is identification of DNA methylation changes, associated with haematogenous metastasis and dormancy and application of novel methods of epigenetic editing CRISPR/dCas9 for their targeting and restoration of normal gene expression. Characterization of epigenetic regulation and signalling pathways involved in UM metastasis can help to identify novel therapeutic targets. Detection of tumour-specific DNA methylation in peripheral blood will allow application of tailored treatment strategies.
Duration:	1.8.2018 - 30.6.2022

Mineralocorticoid receptors in novel target tissues – pathophysiological relevance and underlying mechanisms
Mineralokortikoidné receptory v atypických cieľových tkanivách - patofyziologický význam a zúčastnené mechanizmy
Program:	VEGA
Project leader:	RNDr. Hlaváčová Nataša PhD.
Duration:	1.1.2019 - 31.12.2021

Molecular biomarkers of relapse in seminoma clinical stage I patients
Molekulárne biomarkery relapsu pri seminómoch klinického štádia I
Program:	Other projects
Project leader:	Mgr. Chovanec Miroslav PhD.
Annotation:	Clinical stage I seminoma (S-CS I) patients have a very good prognosis, reaching 98% survival. However, a small proportion of these patients relapse and the prognosis of these patients is significantly worse. There are currently no reliable biomarkers that stratify S-CS I patients, although primary tumor size ≥ 4 cm and rete testis invasion (RTI) are considered to be negative prognostic factors. The present project aims to identify molecular biomarkers that timely and accurately stratify S-CS I patients according to the risk of relapse. We intend to find molecular biomarkers of RTI, whose expression significantly associates with the risk of relapse in S-CS I patients. The factors of poor prognosis in S-CS I will further be sought within DNA repair processes, where the levels of DNA repair proteins will be correlated with the level of their regulation through epigenetic mechanisms and hypoxia. We will also examine proliferative activity as well as lymphocyte infiltrate in S-CS I patients. To achieve these goals, a comprehensive interdisciplinary approach using a wide range of methods and biological material will be used.
Duration:	1.10.2019 - 21.12.2022

Molecular immunerecognition of viral UL144 glycoprotein by endogenous signaling molecules and their clinical potential
Molekulárne imunorozpoznávanie vírusového UL144 glykoproteínu endogénnymi signálnymi molekulami a ich klinický význam
Program:	VEGA
Project leader:	Mgr. Nemčovičová Ivana PhD.
Annotation:	Viruses have evolved elegant mechanisms to evade detection and destruction by the host immune system. One of the evasion strategies that have been adopted by large DNA viruses is to encode homologues of endogenous molecules that have a crucial role in control of the immune response. As our main objective, we will closely examine the MOLECULAR BASIS OF IMMUNE RECOGNITION OF CLINICALLY RELEVANT GLYCOPROTEIN UL144 ENCODED BY HCMV. In this regard, we are planning a preparation, characterization, expression and purification of selected set of recombinant viral and human genes that are associated with cytotoxicity and viroprotectivity processes in the cell. The study of viral immunomodulatory proteins might help us to uncover new human genes that control immunity, and their characterization will increase our understanding of not only viral pathogenesis, but also normal immune mechanisms. Moreover, viral proteins indicate strategies of immune modulation that might have therapeutic potential.
Duration:	1.1.2018 - 31.12.2021

Tumor heterogeneity in multiple myeloma: evolution and clinical relevance
Nádorová heterogenita v mnohopočetnom myelóme: evolúcia a klinická významnosť
Program:	SRDA
Project leader:	RNDr. Jakubíková Jana PhD.
Annotation:	Tumor heterogeneity is likely, from a Darwinian-selection perspective, to be the essential feature of clonal evolution, disease progression and relapse. The existence of intra-clonal heterogeneity resulting from clonal selection has been recently reported in multiple myeloma (MM). Multiple myeloma (MM) is a B cell malignancy characterized by clonal proliferation of plasma cells in the bone marrow (BM). It remains incurable despite improved survival after development of novel therapies. The overall objective of this proposal is to better understand clonal architecture of primary patient-derived BM samples during the development of MM and therapy induced intra-clonal dynamics during progression of MM. A central component of these studies is evolution of BM patient samples from premalignant stages to malignant stages by combining genetic, molecular and phenotypic approaches. We also will evaluate the impact of chemotherapy and immunotherapy on the dynamic nature of the clonal composition together with the role of the tumor microenvironment on clonal selection in MM. To reveal insights into inter- and intra-clonal heterogeneity in MM, the study will provide the framework for development of more personalized diagnostic criteria and novel therapeutic strategies against coexisting persistent subclones resulting in a more individualized targeted therapy to either maintain long-term remission or complete elimination of MM disease.
Duration:	1.7.2017 - 30.6.2021

Gold nanoparticles: impact of physicochemical properties on distribution, accumulation, and biological response in vivo (BIONANOGOLD)
Nanočastice zlata: vplyv fyzikálno-chemických vlastností na ich distribúciu, akumuláciu a biologické účinky in vivo (BIONANOGOLD)
Program:	SRDA
Project leader:	Mgr. Bábelová Andrea PhD.
Annotation:	The BIONANOGOLD project is dedicated to the study of biological effects and bio-distribution of gold nanoparticles (AuNPs) in the living system. The main focus of the project is to understand the relation between physicochemical properties and biological activity of the nanoparticles. The goal is to identify the parameters of AuNPs that are responsible for distribution, accumulation and elimination of the nanoparticles from the body. The integral part is evaluation of the distribution of the nanoparticles in vivo in a short- and a long- term perspective with the respect to their physicochemical properties. At the same time, the characterization of organ/tissue specificity involved in preferential nanomaterial accumulation will be performed. Knowledge of such causality on the material as well as biological levels would comprise the purpose-oriented basis for optimization of gold nanoparticle properties towards therapeutic application. Multidisciplinary character of the project holds a great promise to provide the novel important line of integrated knowledge from the nanoparticle preparation over their characterization in the stock solutions (water, preparation solution) and biological solutions (media, blood plasma), distribution and accumulation in the living organism, to the identification of their biological response. These will bring a great input to the nanomedicine research area and will gain a new insight into the specific interactions of AuNPs with the biological material (nano:bio interactions) that would greatly contribute to the design optimization of the next generation therapeutic nanoparticles. This project would to the deep extent contribute to elucidation of urgent and so far unanswered questions that limit broader clinical use of nanotherapeutics.
Duration:	1.7.2017 - 30.6.2021

Neurobiological research of cancer: Investigation of bi-directional interactions between the nervous system and the tumor
Neurobiologický výskum nádorových chorôb: Skúmanie obojsmerných interakcií medzi nervovým systémom a nádorom
Program:	SRDA
Project leader:	Ing. Tillinger Andrej PhD.
Annotation:	The modulatory effect of the nervous system on tumor growth is currently a generally accepted fact. However, in the treatment of oncology patients, the findings from the research of neurobiology of tumors are not used more substantially. This is due to a number of still unanswered questions. It is unclear what type of nerves innervate the tumor tissue, whether it is possible by affecting the tumor innervation to limit its growth or by what mechanisms the nervous system contributes to the development of tumor cachexia. The aim of the proposed project is to answer these questions and to create the basis for applying the acquired knowledge to clinical practice.
Duration:	1.8.2018 - 31.7.2022

Neuronal regulation of postnatal neurogenesis: a morphological study
Neuronálna regulácia postnatálnej neurogenézy: morfologická štúdia
Program:	VEGA
Project leader:	RNDr. Račeková Enikö CSc.
Duration:	1.1.2019 - 31.12.2021

The neuroprotection of synergic effect of the AT1 receptor blockade and AT2 receptor stimulation after traumatic spinal cord injury
Neuroprotektívny vplyv synergického pôsobenia blokovania AT1 a stimulácie AT2 receptorov po traumatickom poranení miechy
Program:	SRDA
Project leader:	RNDr. Pavel Jaroslav PhD.
Annotation:	Spinal cord injury (SCI) usually causes permanent and often devastating neurologic deficits and disability. Despite a neuroprotective effects in experimental studies, most of the promising therapies fail in clinical studies and up to present time, efficient and trustworthy clinical treatment available for SCI patient is still missing. An essential prerequisite for finding effective therapy is a thorough knowledge of mechanisms that are ongoing in the spinal cord under physiological as well as pathological conditions. Angiotensin II, as main effective hormone of the renin-angiotensin system (RAS) exerts its effect through stimulation of two major receptor types: AT1 and AT2. The majority of physiological as well as pathological processes associated with Angiotensin II are mediated through AT1 receptor stimulation. AT1 receptor blockers are, among other things, a strong neuroprotective substances, what is supported by the results of many scientific experiments. Angiotensin II receptor type 2 (AT2) is absent or very sparsely expressed in most tissues under physiological conditions, however, it is strongly up-regulated after tissue damage. Recently published studies indicated a neuroprotective effects of AT2 receptor stimulation under various pathological conditions. Despite the progress, the precise mechanisms of AT2R action are still not very well known, and its role is controversial. The proposed project contributes to clarify the role of AT2 receptor in neuroprotection and it assumes a substantially more neuroprotective effect of synergic AT2 receptor stimulation and AT1 receptor blockade after experimental trauma-induced spinal cord injury.
Duration:	1.7.2019 - 30.6.2023

New glucoconjugate-based precursors of pharmaceuticals: structure-activity relationship analysis
Nové prekurzory pre farmaceutiká na báze glykokonjugátov
Program:	VEGA
Project leader:	RNDr. Gábelová Alena CSc.
Annotation:	This project is focussed on the structural analysis as well as photochemical, antioxidant, cytotoxic and antiproliferative properties of the new synthetic saccaride derivatives (heparin-like and chitosan-like saccharides bearing quaternary ammonium groups, N-aryl and N-heteroaryl aromatic compounds and their glucoconjugates). NMR spectroscopy will be the main experimental methods but EPR, UV and FTIR spectroscopies, as well as the methods of theoretical chemistry (DFT geometry optimisation, calculation of NMR parameters), will be used for this purpose. Carbohydrate derivatives will be prepared using new synthetic methods applying the transition metal catalysis, microwave field and the ultrasound effects. Polysaccharide derivatives, in the form of films, will be studied also by SEC-MALS as well as by mechanical tests. Apart from the photochemical and antioxidant properties, cytotoxicity and genotoxicity of the selected glycoconjugates will be tested as well.
Duration:	1.1.2018 - 31.12.2021

Newly syntethized thymol derivatives: relationship between structure and biological activity in colorectal in vitro model.
Novosyntetizované deriváty tymolu: vzťah medzi štruktúrou a biologickou aktivitou na in vitro modeli čreva.
Program:	VEGA
Project leader:	RNDr. Kozics Katarína PhD.
Annotation:	Beneficial effects of thymol (TY), a naturally occurring phenol monoterpene of essential oil from thyme, on human health are well known for many years. It is widely used in medical practices, cosmetics, agriculture and as a natural remedy. However due to its low solubility in aqueous media its use e.g. in food industry is limited. The proposed project is focused on the synthesis of hydrophilic derivatives of TY while the antioxidative and antiproliferative properties as well as the effective cellular uptake will remain intact. Using comprehensive approaches from biochemistry, biology, and molecular biology will enable us to assess the biological effects of these derivatives depending on their molecular structure. The project will contribute to gain an insight into the molecular mechanisms of action of hydrophilic TY derivatives. The biological activity will be studied using 2D and 3D colorectal cell models cultured in vitro.
Duration:	1.1.2020 - 31.12.2023

New insight into the phase variation phenomenon of Coxiella burnetii
Nový pohľad na fenomén fázovej premeny u Coxiella burnetii
Program:	VEGA
Project leader:	Ing. Škultéty Ľudovít DrSc.
Annotation:	Coxiella burnetii, a highly pleomorphic intracellular Gram-negative bacterium, causes multiple outbreaks of Q fever worldwide, each year. Human Q fever, generally resulting from inhalation of infectious aerosols produced by domestic animals, exhibits a wide spectrum of clinical manifestations. The bacterium undergoes a host-dependent phase transition. However, redistribution of lipopolysaccharide (LPS) molecules have been observed due to an increasing prevalence of those cells in l population that express LPS with truncated O-chains, the nature of this phenomenon has not been yet sufficiently elucidated. Thus, we believe that isolation of the cell population propagated under various nutritional conditions as well as the clones of spontaneous LPS mutants, followed by identification and ccharacterization of differentially presented proteins and changes in LPS structure, will provide an important insight into the molecular mechanisms underlying this transition and reveal novel diagnostic antigens or therapeutics.
Duration:	1.1.2019 - 31.12.2022

Of Sheep, Goats and Tick-borne Encephalitis virus
O ovciach, kozách a víruse kliešťovej encefalitídy
Program:	SRDA
Project leader:	RNDr. Ličková Martina PhD.
Annotation:	Emerging tick-borne encephalitis from May this year in eastern Slovakia, has been the largest in number of cases for the last five years. As usual, it was supposed that products from raw sheep's milk had been the causative agens. Such enormous epidemic is striking due to the regular routine screening of sheep milk. We have known many foodborne infections from history, but most of cases was related to goat's milk. The aim of the proposed project is a comparative analysis involving sheep respectively goats foodborne infections. With regard to exact criteria it will be selected a representative number of farms from all Slovakia. We will investigate the milk of sheep and goats, as well as ticks collected from direct observation of the animals. It will be done for each farm. Sample will be examined by highly sensitive molecular biological methods for the virus presence. From animal blood we evaluated the serological status of all investigated animals. Evaluation of the results we can see how engaged sheep and goats in the case of food-borne infections. In the case of virus positive samples by sequencing analysis we obtain very valuable information about the genetic diversity of the TBEV in our country. An equally important outcome of the project will be specific methodological recommendations for farmers in terms of preventing foodborne disease.
Duration:	1.7.2017 - 30.6.2021

Unravelling the mechanisms of post-translational regulation of RNA splicing factors in maintenance of genome integrity
Objasnenie mechanizmov posttranslačnej regulácie faktorov zostrihu RNA pri udržiavaní stability genómu
Program:	SRDA
Project leader:	Ing. Čipák Ľuboš PhD.
Annotation:	Several mutations in RNA biogenesis factors have been implicated in human cancers. Early studies linked RNA processing defects with genome instability phenotypes such as hyper-mutation and hyper-recombination. Since then, recent functional genomic studies have implicated several more aspects of RNA processing in genome instability and revealed that virtually every major aspect of RNA processing is potentially mutable to a genome instability phenotype and in some cases are coupling RNA processing defects to increased RNA:DNA hybrid mediated R-loop formation, which in turn constitute a major source of genome instability across species. Despite it is now clear that RNA processing defects could destabilize genomes, the molecular mechanism of post-translational regulations of RNA processing and its connections to genome instability are not clear. Our project is aimed at a detailed analysis of the regulatory role of phosphorylation for functions of splicing factors that co-purified with the recently identified spliceosome-associated Nrl1 protein of fission yeast S. pombe. We showed Nrl1 protein be involved in suppression of accumulation of genome threating RNA:DNA hybrids, structures formed during RNA processing. The experimental approaches include protein purifications and phospho proteomics analysis, which will help us to identify post-translational modifications of splicing factors. Analysis of phenotypes of phospho mutants of splicing factors employ fluorescence/live-cell microscopy, analysis of splicing defects of these mutants using RT-qPCR or transcriptome sequencing, followed by analysis of their sensitivity to DNA damaging agents and analysis of their defects in DNA repair pathways. The obtained data should bring especially completely new information concerning the regulatory roles of post-translational modifications associated with the defects of RNA processing leading to genome instability that may be important as possible targets for anti-cancer therapy.
Duration:	1.7.2017 - 30.6.2021

Unraveling the role of genetic predispositions in the context of breast cancer tumor microenvironment
Objasnenie úlohy genetických predispozícií v kontexte nádorového mikroprostredia karcinómu prsníka
Program:	VEGA
Project leader:	Mgr. Cihová Marína PhD.
Duration:	1.1.2020 - 31.12.2023

Unraveling the mechanisms linking obesity and cancer progression: the interplay between adipocytes and cancer cells
Odhalenie mechanizmov spájajúcich obezitu s nádorovou progresiou: interakcia medzi adipocytmi a nádorovými bunkami
Program:	VEGA
Project leader:	RNDr. Takáčová Martina PhD.
Annotation:	Obesity is a major public health concern because it increases the risk of several diseases, including cancer. Crosstalk between obesity and cancer seems to be very complex, potentially acting directly on cells, or indirectly via changes in the tumor microenvironment. One of the proposed mechanisms underlying the risk association is the adipocyte-mediated secretion of adipokines. Adipokines, acting locally or systemically, play important roles in the growth, local invasion, metastatic spread, and resistance to treatment of different types of cancer. Therefore, a great interest exists to understand the molecular mechanisms by which adipocytes contribute to carcinogenesis. This project will examine on the impact of adipokines on the biological characteristics of cancer cells exposed to hypoxia and/or acidosis, focusing on carbonic anhydrase IX that is a well-known marker of tumor hypoxia, expression of which significantly correlates with poor prognosis and resistance to therapy.
Duration:	1.1.2020 - 31.12.2023

Disclosure of the molecular mechanism of spontaneous tumor regression followed by the development of novel prognostic tool
Odhalenie molekulárneho mechanizmu spontánnej regresie nádorov s nasledným vývojom nového prognostického nástroja
Program:	SRDA
Project leader:	MUDr. Lakota Ján CSc.
Annotation:	Spontaneous regression of tumor is a phenomenon that was reported in virtually all types of human malignancies. Recently, our team has observed this anti-tumor activity after high dose therapy and autologous stem cell transplantation in patients with Hodgkin’s disease, multiple myeloma, and some other malignancies. It seems to be associated with aplastic anemia like syndrome and ongoing pancytopenia induced by autoimmunity directed against hematopoietic stem cells. To understand the interconnected processes occurring in vivo we need to detect, identify, and structurally characterize clinically essential molecules involved in the depletion of tumor cells or tumors as a whole. We will therefore perform a systematic comparative proteomic analyses of control and treated (with polyclonal Abs of patients in regression/specific mAbs or other discovered target molecules) tumor cells. The obtained results will allow to reveal essential molecules associated with induction of tumor regression and recognize prognostic markers useful for monitoring the disease development. These finding will not only lead to a deeper understanding of this phenomenon at the molecular level, but in the link with novel information obtained from protein-protein interaction studies based on advanced proteomic analyses will contribute to future targeted therapy of certain malignancies and to design a valuable diagnostic tool for monitoring the progress of the disease.
Duration:	1.7.2019 - 30.6.2023

Open scientific community for modern interdisciplinary research in medicine
Otvorená vedecká komunita pre moderný interdisciplinárny výskum v medicíne
Program:
Project leader:	RNDr. Gálik Ján CSc.
Annotation:	The project proposal aims to create a complementary scientific-research biomedical structure and in the consortium - which consists of UPJŠ Košice, UVLF Košice, NbÚ BMC SAV, TUKE Košice, Advanced Diagnostic Focus p. r. about. (ADF) and Hospital Košice-Šaca a.s. 1. private hospital (Šaca Hospital) - to solve scientific biomedical problems divided into three activities: nanomedicine (biomedical engineering), regenerative medicine and personalized diagnostics. Instrumentation and expertise will be provided in the project through central specialized technology platforms: Optical bio-imaging, Tissue and cell laboratory, Experimental vivarium, Histological Laboratory, Laboratory of Biochemical and Molecular Analyzes and Laboratory of Additive Biomedical processes. The project will be solved in the laboratories of UVP MEDIPARK UPJŠ, CIB UPJŠ, laboratories built during the implementation of OP R&D in UPJŠ, NbÚ BMC SAS, UVLF and with the help of capacities and expertise of commercial partners in the project. The main output indicators are generally definable at two levels: i) launch of some technology platforms and ii) realization of scientific objectives, which we generally characterize as: a) research and development (R&D) of drug delivery systems, b) R&D of adult stem cells and development of modern methods of cell treatment, c) R&D of imaging procedures and teranostic nanoparticles for biomaterials, cells and tissues, d) R&D of modern 3D printed tissue replacements and cell carriers, e) R&D of new approaches in CNS and nervous tissue regeneration, f) R&D in areas of new diagnostic procedures for precise personalized diagnostics, g) R&D in the field of diagnostics of selected viral infections and h) R&D in the field of interconnection of medical imaging systems with a database knowledge system. The main goal - the application of research results in practice and in the commercial area is ensured by the cooperation of the applicant with commercial partners who provide the clinical and basic research part of the project.
Duration:	1.11.2019 - 30.6.2023

Effect of physical activity and nutrition on gut microbiota modification in healthy subjects and patients with a non - communicable diseases
Ovplyvnenie črevnej mikrobioty telesným pohybom a stravou v zdravej populácii a u pacientov s neprenosnými chronickými ochoreniami
Program:	SRDA
Project leader:	MUDr. Penesová Adela PhD.
Duration:	1.8.2018 - 30.6.2022

A pilot study of the selective effects of a new generation of RNA interfering agents at the cellular level
Pilotná štúdia selektívneho pôsobenia novej generácie RNA interferenčných agens na bunkovej úrovni
Program:	VEGA
Project leader:	Mgr. Šelc Michal PhD.
Annotation:	The proposed project is based on the in-depth understanding of the current scientific and clinical knowledge of chronic myelogenous leukemia (CML) and the therapeutic regimens based on RNA interference. The project aims at a highly ambitious goal: to explore the selective effect of a novel platform of RNA interfering agents at the cellular level in order to evaluate its therapeutic potential for action without side effects that would result from undesired molecular interactions. From this perspective, the project focuses primarily on an extensive study of cellular internalization, inhibition of the formation of fusion BCR-ABL1 protein, selectivity of RNA interfering agents towards the target mRNA and its effect in cells resistant to currently applied therapeutics.
Duration:	1.1.2020 - 31.12.2023

Potential risk of use of analogs of endocrine disruptor Bisphenol A: determination of cellular and molecular effects in a spectrum of in vitro gonadal cell cultures
Potenciálne riziko používania analógov endokrinného disruptoru Bisfenolu A: hodnotenie účinkov na bunkovej a molekulovej úrovni v spektre in vitro gonadálnych bunkových kultúr
Program:	SRDA
Project leader:	Mgr. Bujňáková Mlynarčíková Alžbeta PhD.
Duration:	1.7.2019 - 30.12.2022

GLP-1 analogues usage in the treatment of multiple sclerosis
Použitie GLP-1 analógov v terapii sklerózy multiplex
Program:	Other projects
Project leader:	doc. MUDr. Imrich Richard DrSc.
Duration:	1.12.2018 - 31.3.2021

Preclinical validation of an innovative antisense platform for CML
Predklinická validácia inovatívnej antisense platformy pre CML
Program:	SRDA
Project leader:	Mgr. Bábelová Andrea PhD.
Annotation:	Currently, chronic myelogenous leukemia (CML) is widely treated with tyrosine kinase inhibitors (TKIs) that effectively inhibit proleukemic activity of the causal BCR-ABL oncoprotein. However, long-term clinical experience with TKIs shows that these drugs are not sufficiently selective and specific for CML cells and BCR-ABL, respectively. This phenomenon often results in clinically significant adverse events responsible for deterioration of TKI treatment outcomes and decreased quality of life. Moreover, limited therapeutic effect of TKIs towards CML stem cells cause that patients with CML are in most of the cases long-term treated, but not completely cured. The development of alternative treatment strategies that exclusively target only CML cells and provide a possibility of permanent cure, is therefore of paramount need. The proposed PRO4CML project is directly related to the successful APVV-15-0215 project (total IF of the scientific output > 80), which was aimed at testing of an innovative antisense concept for BCR-ABL silencing in patients with CML. Thanks to its original design and mechanism of action, this progressive concept showed unprecedented potential in terms of selective recognition of target nucleic acid and, most importantly, exceptional translational potential in terms of selective biological action exclusively in tumor cells. Since the conceptual solution is fully universal, it is expected to overcome the major obstacles that have so far hindered antisense therapeutics from entry to clinical practice. The PRO4CML project is thus a natural continuation of the scientific work of the project consortium and represents the cornerstone for robust in vivo preclinical validation. If successful, the proposed concept is also expected to provide an original therapeutic platform not only in CML but also in other diseases with known molecular basis, where a particular protein plays a causal role in disease pathophysiology.
Duration:	1.7.2020 - 30.6.2024

Bridge between the mental state and neuroendocrine function of mother and her child: the mechanisms involved
Premostenie psychiky a neuroendokrinných funkcií matky a jej dieťaťa: zúčastnené mechanizmy
Program:	SRDA
Project leader:	prof. PharmDr. Ježová Daniela DrSc.
Duration:	1.7.2019 - 30.6.2023

Reprogramming of host cell metabolism induced by lymphocytic choriomeningitis virus infection
Preprogramovanie metabolizmu hostiteľskej bunky vyvolané vírusom lymfocytovej choriomeningitídy
Program:	VEGA
Project leader:	Ing. Tomášková Jana PhD.
Annotation:	Viral replication depends on the energy and biosynthetic precursors supplied by the host cell metabolic network. Viruses actively reprogram host cell metabolism to establish optimal environment for genome replication, virion production, and enhanced survival of infected cells. While there are common metabolic changes induced by most viruses studied, there are also unique virus-specific metabolic modifications. Therefore, it is crucial to perform a detailed study for each virus species to understand these specific metabolic changes. The main goal of the proposed project is to reveal how lymphocytic choriomeningitis virus (LCMV) modulates host cell metabolic processes to ensure successful infection. We will focus mainly on LCMV-induced changes in central carbon metabolism. Understanding how LCMV reprograms cellular metabolism will provide new information on the biology and pathogenesis of LCMV and other arenaviruses. Moreover, it may open new strategies to combat pathogenic arenaviruses through targeted inhibition of specific cellular metabolic pathways.
Duration:	1.1.2019 - 31.12.2022

Prevention and mechanism of synergy of influenza and bacterial coinfection
Prevencia a mechanizmus synergie chrípkovej a bakteriálnej koinfekcie s ťažkým priebehom ochorenia.
Program:	SRDA
Project leader:	RNDr. Varečková Eva DrSc.
Annotation:	Influenza A viruses are responsible for yearly repeated respiratory disease of humans, which spreads in the form of epidemics or pandemics. Influenza disease is frequently accompanied by complications related to the damage of the epithel of the respiratory tract (airways), resulting in life-threatening pneumonia of viral origin. However,the reason for such serious clinical state after the influenza infection can be related to the secondary bacterial infection, predominantly with Streptoccoccus pneumoniae, Haemophilus influenzae, or Staphylococcus aureus. The pathogenetic process triggered by influenza infection creates a suitable environment for the establishment of subsequent bacterial infection, which is usually severe and can have a fatal outcome. Our knowledge about of the mechanism of these processes is, however, very poor. Therefore the subject of our interest in the submitted project will be the study of the synergy of viral and bacterial infection on mouse model. We shall focus on the main parameters of immunity, which plays a pivot role in the severity of the infection. The second goal will be the study of factors modulating the interaction of viral and bacterial co-infection with the accent on the anti-influenza vaccination with conserved viral antigens, taking into account an associated host factor - obesity. As a viral model we shall use influenza A viruses of different pathogenicity of H1, H3, and H7 subtypes and as a bacterial model will be used Streptococcus pneumoniae. We expect that the project brings new original theoretical results concerning the knowledge of the mechanism of interaction of viral and bacterial infection, and simultaneously it can show the way how to lower the risk of severe, even fatal, course of viral and bacterial co-infection in immune compromised patients or in patients suffering from other health disorders like chronic cardiovascular disease or obesity.
Duration:	1.8.2018 - 30.6.2022

Preparation of new antibiotics and antitumor agents by manipulations of secondary metabolite genes and synthetic biology methods
Príprava nových antibiotík a protinádorových látok manipuláciami génov sekundárnych metabolitov a metódami syntetickej biológie
Program:	SRDA
Project leader:	RNDr. Jakubíková Jana PhD.
Duration:	1.7.2020 - 30.6.2024

Dbl2 protein as a novel regulator of genome stability and dynamics in fission yeast
Proteín Dbl2 ako nový regulátor stability a dynamiky genómu v kvasinkách Schizosaccharomyces pombe
Program:	SRDA
Project leader:	Ing. Čipák Ľuboš PhD.
Duration:	1.7.2019 - 30.6.2022

Radiation-induced preleukemic fusion genes in proliferating hematopoietic stem/progenitor cells of umbilical cord blood
Radiačne-indukované preleukemické génové fúzie v deliacich sa hematopoetických kmeňových/progenitorových bunkách pupočníkovej krvi
Program:	VEGA
Project leader:	RNDr. Škorvaga Milan CSc.
Annotation:	Preleukemic fusion genes (PFG) resulting from chromosomal translocations are often the primary genetic lesion in the development of childhood acute leukemia. The PFG originate in hematopoietic stem/progenitor cells, often in utero. It is known that high doses of ionizing radiation (IR) can cause leukemia. However, there are no data on the effects of low doses of IR to which the population may be exposed. Our preliminary experiments on non-dividing mononuclear cells of umbilical cord blood (UCB) indicate that low doses of IR cause some degree of PFG induction. In this project CD34+ cells isolated from UCB will be irradiated by high and low doses of ionizing radiation, expanded and then tested for the presence of diagnostically relevant PFG (with R-T qPCR and FISH methods) and 'hotspot' substitution mutations in the TP53 gene (using 'restriction-site mutation' method). Our aim is to determine whether the dose of IR affects the incidence and spectrum of PFG and TP53 mutations.
Duration:	1.1.2018 - 31.12.2021

Tubular conduits for axonal regeneration after peripheral nerve injury.
Regenerácia axónov poškodeného periférneho nervu v tubulárnych vodičoch
Program:	VEGA
Project leader:	MVDr. Vanický Ivo CSc.
Duration:	1.1.2020 - 31.12.2022

Regulation of pyruvate dehydrogenase kinase 1 activity in the control of glycolytic metabolism in hypoxic tumors
Regulácia aktivity pyruvát dehydrogenázy kinázy 1 pri ovplyvňovaní glykolytického metabolizmu v hypoxických nádoroch
Program:	VEGA
Project leader:	PharmDr. Goliaš Tereza PhD.
Annotation:	Hypoxic tumor microenvironment actively shifts metabolism from oxidative to glycolytic in cancer cells. This adaptation is believed to conserve oxygen and metabolic substrates necessary for sustained proliferation, and it also makes tumor cells more aggressive. Apart from upregulating glycolysis, mitochondrial function is also actively downregulated in hypoxia, through the induction of pyruvate dehydrogenase kinase 1 (PDHK1) that inhibits pyruvate dehydrogenase, a gate-keeper enzyme between mitochondrial tricarboxylic-acid cycle and cytosolic glycolysis. We have found that hypoxia not only induces PDHK1 expression but it also acutely regulates its enzymatic activity, although the molecular mechanism remains largely unknown. Since hypoxia elevates cAMP levels, which in turn activate protein kinase A (PKA), and in silico analysis identified putative PKA-phosphorylation sites on PDHK1, we therefore hypothesize that this type of post-translational modification could potentially regulate PDHK1 activity in hypoxia.
Duration:	1.1.2019 - 31.12.2022

Regulation of preadipocyte differentiation and adipocyte metabolism by oxidative stress in rat and human tissue culture.
Regulácia diferenciácie preadipocytov a metabolizmu adipocytov oxidačným stresom v potkanej a ľudskej bunkovej kultúre.
Program:	VEGA
Project leader:	Ing. Zorad Štefan CSc.
Duration:	1.1.2020 - 31.12.2022

Regulation of epithelial-mesenchymal transition by microRNA and promoter methylation in invasive breast cancer
Regulácia epiteliálno-mezenchymálneho prechodu prostredníctvom mikroRNA a metylácie promótorov v invazívnych nádoroch prsníka
Program:	VEGA
Project leader:	RNDr. Fridrichová Ivana CSc.
Annotation:	High breast cancer mortality evokes the necessity of new biomarkers for more effective management of metastatic disease. The aim of project is to investigate the effect of aberrant methylation profiles in the epithelial-mesenchymal transition genes (TWIST1, SNAI1 and SNAI2) and changed expression of their eight regulating microRNAs on the expression of CDH1 gene encoding the main cell-cell adherent protein E-cadherin. To characterize the cancer cell populations associated with haematogenous or lymphogenous dissemination, we will study epigenetic changes in two locations of invasive tumours (central and invading front), in metastatic lymph nodes and circulating tumour cells compared to the non-invasive tumours and controls. In the case of correlations with clinico-pathological data, the specific DNA methylation or microRNA expression profiles could serve for metastatic potential monitoring. In addition, targeted sample selection for analysis of cancer invasivity allows to identify more reliable biomarkers.
Duration:	1.1.2019 - 31.12.2022

Regulation of the Swi5-Sfr1 complex by protein phosphorylation
Regulácia komplexu Swi5-Sfr1 pomocou fosforylácie
Program:	SRDA
Project leader:	Ing. Čipáková Ingrid PhD.
Annotation:	Homologous recombination is important for repair of damaged DNA in vegetative cells but is also required for proper segregation of chromosomes during meiosis, a specialized cell division, which produces haploid gametes such as eggs and sperm cells in mammals and spores in yeast. Swi5-Sfr1 heterodimer complex stimulates the Rad51-mediated exchange of DNA strands, a key step in homologous recombination. We have identified swi5 and sfr1 deletion mutants in a screening for mutants defective in chromosome segregation during meiosis in the fission yeast Schizosaccharomyces pombe. Our initial characterization revealed new phosphorylation sites on both Swi5 and Sfr1. In this project, we want to decipher how phosphorylation regulates the role of Swi5 and Sfr1 in both vegetative and meiotic S. pombe cells. This will help us to understand the process of homologous recombination and reduction of chromosome number during meiosis. Both Swi5 and Sfr1 proteins are evolutionarily conserved, raising the possibility that our results will be relevant to studies in various organisms including mammalian cells.
Duration:	1.8.2018 - 30.6.2022

Regulation of M1/M2 polarization: the effect on neuron survival, axonal growth and functional recovery after spinal cord trauma
Regulácia M1/M2 polarizácie: vplyv na prežitie neurónov, rast axónov a funkčnú obnovu po poranení miechy
Program:	VEGA
Project leader:	RNDr. Lukáčová Nadežda DrSc.
Annotation:	Proposed project is aimed to 1) study molecular changes that regulate transformation of neuroinflammatory M1 microglia to A1 astrocytes in acute/subacute phase after Th9 compression, 2) characterize time-dependent regulation of M1/M2 polarization, a key factor in activation of pro-regenerative molecules, 3) investigate selected markers for identification of pro-inflammatory cytokines, infiltration of M1/M2 macrophages, activation of resident cells (astrocytes and microglia) and infiltration of lymphocytes in the spinal cord, blood serum and in the small intestine after Th9 compression and antibiotics, probiotics and anti-inflammatory treatment. To determine which of mechanisms regulates M1/M2 polarization, and which signaling pathways (P13K/Akt; PLC-γ/CAMK a PLC-γ/PKC) are responsible for neuroplasticity and cells survival. To investigate neuroregenerative and neuroprotective effect of treatment on tissue integrity, axonal sprouting, synaptic activity and functional recovery in chronic stage of SCI.
Duration:	1.1.2021 - 31.12.2023

Regulation of Pericellular Proteolysis: From Molecular Mechanisms To Novel Immune Cell Subsets and Therapeutic Tools
Regulácia pericelulárnej proteolýzy: od molekulárnych mechanizmov k novým subsetom imunitných buniek a terapeutickým nástrojom
Program:	SRDA
Project leader:	RNDr. Zahradníková, ml. Alexandra PhD.
Duration:	1.7.2017 - 30.6.2021

Neurotransmitter-mediated regulation of postnatal neurogenesis in the rat olfactory system under physiological and pathological conditions
Regulácia postnatálnej neurogenézy v čuchovom systéme potkana prostredníctvom neurotransmiterov za fyziologických a patologických podmienok
Program:	SRDA
Project leader:	RNDr. Račeková Enikö CSc.
Annotation:	The regulatory mechanisms of postnatal neurogenesis in the olfactory neurogenic area of the mammalian brain - the subventricular zone (SVZ), rostral migratory stream (RMS) and olfactory bulb (OB) are still not fully understood. The project is focused on investigation of neurogenesis regulation via neurotransmitters nitric oxide and serotonin in this neurogenic region under physiological conditions and in rat model of depression. We intend to reveal neuronal circuits of nitric oxide producing neurons localized within the rat RMS, which should contribute toward the understanding of neuronal regulation of postnatal neurogenesis. To date, the association between decreased serotonin levels due to depression and reduced neurogenesis has been demonstrated only in the hippocampus. Our experiments are aimed to investigate the link between depression, altered serotonin regulation and neurogenic processes in the olfactory neurogenic area. Detailed analysis of integral components of microenvironment in the SVZ in animals with induced depression enables us to reveal the processes of regulation of neurogenesis in pathologically altered conditions. New knowledge in this area could potentially reveal promising targets for novel therapies aimed to disorders associated with changes in adult neurogenesis.
Duration:	1.7.2020 - 30.6.2024

Rickettsiae and Coxiella burnetii, bacterial triggers of the “mysterious“ diseases
Rickettsiae a Coxiella burnetii, bakteriálne spúšťače
Program:	VEGA
Project leader:	RNDr. Sekeyová Zuzana PhD.
Annotation:	In certain types of diseases with no clear way of developing are bacteria considered as "triggers" of various ills. They are referred to a number of data indicating a synergistic action of bacterial infections on the human body. Moreover, certain bacteria, R. prowazekii from rickettsiae and C. burnetii, were included among the potential bio-terrorist weapons. The detection of the causal causes of bacterial infections in neuropathies (rickettsiae) and cardiovascular diseases (C. burnetii), on the serological, molecular and transkriptomic basis, has therefore a major medical importance and is a scientific challenge. We will concentrate our forces on the clarification of the pathomechanisms of their interaction at the cellular level; reveal specific patterns and abnormal growth of infected cells, forthcoming disorders due to rickettsial and/or Q fever infection, as well as the structure, i.e. genes coding for "pathologically responsible" proteins. Our knowledge will subsequently be put in a diagnostic practice.
Duration:	1.1.2019 - 31.12.2022

Monitoring of ibrutinib effectivity applied in B-cell type malignancies depending on inflammatory status
Sledovanie efektivity ibrutinibu aplikovaného u B-bunkových lymfoidných malignít v závislosti od zápalového statusu.
Program:	VEGA
Project leader:	RNDr. Bízik Jozef DrSc.
Annotation:	Experimental data obtained in recent years proved a fact that etiology and progression of B-type lymphoid malignancies is linked to the occurrence of inflammation in patients. Therefore the proposed project is focused on study of progression of this type of the tumor cells after being affected by the ibrutinib, an inhibitor of the Bruton´s tyrosine kinase. This kinase is predominantly expressed in B-lymphocytes. The project will be done in the form of a clinical study where circulating inflammatory parameters along with an endogenous anti-inflammatory activity are followed in peripheral blood specimens of treated patients. The latter activity will be assessed by a biochip which evaluates changes in expression of cyclooxygenase-2. Simultaneously we will analyze in vitro a panel of cell lines of B-type influenced by inflammatory conditions an ibrutinib. We propose the gained results will contribute to more effective personalized application of ibrutinib considering the inflammatory status of a treated patient.
Duration:	1.1.2019 - 31.12.2021

Monitoring of tick saliva immunomodulators effects on innate antiviral responses of skin
Sledovanie vplyvu imunomodulačných látok v slinách kliešťov na vrodenú antivírusovú imunitu kože.
Program:	VEGA
Project leader:	Mgr. Štibrániová Iveta PhD.
Annotation:	Skin is the first host organ that tick borne viruses (TBV) and tick saliva encounter during the tick feeding process. Cutaneous resident immune cells (keratinocytes, fibroblasts, macrophages, dendritic cells, leukocytes) play a crucial role in the initial response of the host to tick feeding and invading pathogenic microorganisms, including viruses. Complex interactions between the early phases of host immune response and early tick-mediated immunomodulation at the skin interface are essential in a successful TBV transmission. Thus, tick saliva immunomodulatory components play a crucial role in tick feeding and mediating transmission of TBV. However, information on interactions of host-TBV-ticks are still limited. Understanding of the mode of effect of tick saliva on early immune responses of skin cells mediated by interferons on TBV infection can enable the development of novel strategies to control viral tick-borne diseases
Duration:	1.1.2018 - 31.12.2021

Interrelationships between endocrine and mental characteristics of women in reproductive age
Súvislosti medzi endokrinnými a psychickými charakteristikami žien v reprodukčnom veku
Program:	VEGA
Project leader:	prof. PharmDr. Ježová Daniela DrSc.
Duration:	1.1.2019 - 31.12.2022

Synergistic effects of exercise and carnosine supplementation on motor functions, metabolism and skeletal muscle phenotypes in patients with early stage Parkinson's disease
Synergické účinky cvičenia a suplementácie karnozínom na motoriku, metabolizmus a charakteristiky kostrového svalu u pacientov vo včasných štádiách Parkinsonovej choroby
Program:	VEGA
Project leader:	doc. MUDr. Ukropcová Barbara PhD.
Duration:	1.1.2018 - 31.12.2021

Systemic public research institution - biobank for cancer and rare diseases
Systémová verejná výskumná infraštruktúra – biobanka pre nádorové a zriedkavé ochorenia
Program:
Project leader:	RNDr. Gašperíková Daniela DrSc.
Duration:	1.6.2020 - 30.6.2023

Study of alternative ways of genome-wide polygenic risk score calculations for the estimation of individual genetic predispositions to complex multifactorial diseases
Štúdium alternatívnych spôsobov výpočtov polygénových rizikových skóre na hodnotenie individuálnych genetických predispozícií ku komplexným multifaktoriálnym ochoreniam
Program:	VEGA
Project leader:	RNDr. Radvánszky Ján PhD.
Annotation:	In the field of genomic analyses, the assessment of genomic background of individual patients, in terms of complex multifactorial diseases, is an issue of worldwide interest. Main attention is paid to the design of appropriate calculations of genome-wide polygenic risk scores to determine predispositions to these diseases. We believe that the original, and so far unique, components of the present project are: 1) evaluation of individual patients by stratifying genomic risk factors to discrete biological pathways, specifically calculating partial risk scores for individual pathways; 2) in the context of genomic data from family members, using segregation analyzes. We selected ulcerative colitis, psoriasis and rheumatoid arthritis as model diseases. We plan to study them on multi-generation families, where all these diseases occur separately in different members belonging to different generations, but also in families where these diseases occur at one member comorbidly.
Duration:	1.1.2020 - 30.6.2022

Study of biological effects of H2S/NO/selenium products and molecular mechanisms of their actions
Štúdium biologických účinkov produktov H2S/NO/selénovej interakcie a molekulárne mechanizmy ich pôsobenia
Program:	SRDA
Project leader:	RNDr. Ondriaš Karol DrSc.
Annotation:	Reactive sulfur (RSS), nitrogen (RNS) and selenium species (RSEs) are groups of simple chemical molecules of radical or non-radical nature, which interact with cellular components and thereby influence various biological processes. The study of biological effects of RSS, RNS and RSeS and their mutual interactions is important for the understanding of their biological roles, moreover for the potential application of these species in medicine. Our studies of the reactive species interaction in the last 3 years showed that: - products of hydrogen sulfide (H2S) and polysulfides (H2Sn, n≥2) interaction with nitric oxide (NO) or selenium compounds (R-Se) significantly affect oxygen radicals concentrations, hydroperoxide cleavage, DNA damage, rat blood pressure and tension/relaxation of isolated aorta. - H2S and H2S2 interact with tetracycline antibiotics, mainly doxycycline (DOXY) and thereby produce/inhibit superoxide and hydroxyl radicals and induce/inhibit DNA damage These findings imply the possibility that reactive oxygen species (ROS) and other H2S/NO/R-Se interaction products affect (patho)physiological functions in living organisms. In the project´s aims we will build on the previous findings and investigate following new hypotheses: 1) Do mixtures (H2Sn/R-Se, H2Sn/R-Se/NO alebo H2Sn/DOXY) produce ROS or other biologically active compounds? 2) Are these products responsible for production/inhibition of radicals, cleavage of hydroperoxides and induction/inhibition of DNA damage? 3) Do interaction products affect ferroptosis or intracellular calcium concentration in cells? 4) Do these products affect rat blood pressure, arterial pulse waveform and tension of isolated arteries? The aim of this project is to investigate the chemical biology, activity and effects of the interaction products on cellular, organ and whole-organism level. These findings may contribute to the development of novel therapeutic interventions based on the modulation of cellular redox biology.
Duration:	1.7.2020 - 30.6.2024

The dynamics of inflammation-induced epigenetic changes during epithelial-to-mesenchymal transition and their role in human pancreatic ductal adenocarcinoma progression
Štúdium dynamiky zápalom-indukovaných epigenetických zmien v procese epiteliálno-mezenchymálneho prechodu a ich úlohy v progresii duktálneho adenokarcinómu pankreasu
Program:	VEGA
Project leader:	RNDr. Čierniková Soňa PhD.
Annotation:	The 5-year survival rate in pancreatic ductal adenocarcinoma (PDAC), that accounts for more than 80% of pancreatic cancers, is less than 5%. Inflammation is a key mediator of PDAC development and inducer of epithelial-to-mesenchymal transition (EMT). During tumour progression and malignant transformation EMT allows epithelial tumour cells to acquire mesenchymal, stem cell-like properties, increased migratory capacity, invasiveness and resistance to therapy. The reversibility of EMT can be explained by epigenetic plasticity, that allows dynamic changes of gene expression via DNA methylation, histone modifications and non-coding RNAs. The aim of proposed study is to investigate mechanisms, connecting inflammation and EMT with focus on EMT-associated epigenetic changes. Our findings can contribute to the understanding of PDAC progression and discovery of novel clinical biomarkers. Given the reversible nature of epigenetic regulation, they may aid in the development of more efficient therapeutic targets.
Duration:	1.1.2018 - 31.12.2021

Study of the genetic background of variable severity of Alkaptonuria using genomic approach.
Štúdium genetického pozadia variabilnej závažnosti alkaptonúrie za použitia genomických analýz.
Program:	VEGA
Project leader:	Mgr. Zaťková Andrea PhD.
Annotation:	Genome sequencing can be used for deeper analysis of the genetic background of the disease, for possible studies of the phenotype and genotype correlation. Alkaptonuria (AKU) is caused by mutations in the homogeneisate-1,2-dioxygenase (HGD) gene, while due to the metabolic block homogeneous acid (HGA) is accumulated in the form of so called ochronotic pigment, causing painful multisystemic disease mainly affecting the cartilage of large joints and spinal column (disease-related arthropathy). Recently, we reported different levels of HGA in the urine of the patients that carry mutations causing different residual HGD enzyme activity, while this was not reflected directly at the phenotypic level by the severity of the disease in the mutation carriers. However, there is a marked variability in AKU patients, even within one family, thus other genetic factors are believed to affect the manifestation and progress of the disease. Our project will focus on identification of such variants.
Duration:	1.1.2020 - 31.12.2022

Genetic causes of rare diseases with emphasis on metabolic disorders associated with hypoglycemia and mitochondiopathies
Štúdium genetických príčin zriedkavých ochorení s dôrazom na metabolické poruchy asociované s hypoglykémiami a poruchy mitochondrií
Program:	SRDA
Project leader:	RNDr. Gašperíková Daniela DrSc.
Duration:	1.8.2018 - 31.7.2022

Study of pro-metastatic functions of carbonic anhydrase IX, relationship between CA IX and mucins and hypoxic microenvironment in pancreatic cancer.
Štúdium prometastatických funkcií karbonickej anhydrázy IX, jej vzťahu k mucínom a hypoxického mikroprostredia v rakovine pankreasu.
Program:	VEGA
Project leader:	Mgr. Švastová Eliška PhD.
Annotation:	Pancreatic cancer especially intraductal papillary mucinous neoplasms (IPMNs) are characterized by aberrant expression of different types of mucins. Although the overall prognosis for patients with IPMNs is better than it is for pancreatic ductal adenocarcinoma (PDAC) a subset of patients develops invasive tumors. Carbonic anhydrase IX is hypoxia induced protein whose expression, in many cancers, is associated with higher metastatic potential and poor prognosis of patients, also in cohort of patients with pancreatic ductal adenocarcinoma with lower survival. Genevestigator analysis revealed co-expression of CA9 with mucins (e.g. MUC1, MUC5AC) in IPMNs that progress from adenoma to carcinoma. Characterization of CA IX - mucins relationship and their role in epithelial-mesenchymal transition in pancreatic cancer and the impact of CA IX-related tumor microenvironment on pancreatic cancer progression is essential for adequate therapeutic strategies to overcome this lethal disease.
Duration:	1.1.2019 - 31.12.2022

Study of Exosome Nanoparticle Properties Secreted by Mesenchymal Stromal Cells Transduced by the HerpesSimplex Virus Thymidine Kinase (TK/HSV) Suicide Gene to Be Used for Innovative Glioblastoma Therapy
Štúdium vlastností nanočastíc charakteru exozómov vylučovaných mezenchýmovými stromálnými bunkamitransdukovanými samovražedným génom tymidínkináza vírusu Herpes Simplex (TK/HSV) s cieľom ich využitiana inovatívnu terapiu glioblastomu
Program:	VEGA
Project leader:	doc. Ing. Altaner Čestmír DrSc.
Annotation:	Glioblastoma grade III and IV is the most malignant brain tumor. Surgical removal of the tumor with concomitantradio-chemotherapy does not result in cure. We have shown that mesenchymal stem/stromal cells (MSCs)transduced with the TK/HSV neurotrophic genome in interaction with human glioblastoma cells inhibit their growthin the presence of ganciclovir prodrug. Findings in the field of anti-tumor suicide therapy with fusion yeast gene(cytosine deaminase::phosphoribosyltransferase) by MSC showed that MSC cells secrete exosomes withinformation of the suicide gene (RNA). The aim of the study is to determine whether a similar effect is alsoachieved by transduction of the MSC by gene TK/HSV. The TK/HSV suicide gene exosomes may be the basis forinnovative brain tumor therapy. Thanks to MSC tumor tropism, they will be directed to the tumor and at the sametime due to HSV neural tropism to the neural component of glioblastoma. The aim of the project is to verify thecorrectness of our hypothesis
Duration:	1.1.2020 - 1.12.2022

Turning cisplatin-resistant testiular germ cell tumors into a curable disease
Testikulárne nádory zo zárodočných buniek rezistentné na cisplatinu: ich premena na liečiteľné ochorenie
Program:	SRDA
Project leader:	Mgr. Chovanec Miroslav PhD.
Annotation:	Testicular germ cell tumors (TGCTs) are highly curable malignancy due to their cisplatin (CDDP) sensitivity. CDDP is therefore used as a standard in the first-line chemotherapy of this disease. Nevertheless, a small proportion of patients does not achieve a complete remission after first-line chemotherapy, or relapses. Patients who relapse have a less favorable prognosis, although 20–25% of them can still be cured with conventional second-line CDDP-based chemotherapy. Patients who are not cured with second-line therapy have very poor prognosis. In the present grant, we intend to identify the mechanisms that determine poor response to CDDP in TGCT patients. Therefore, we will compare the mRNA and miRNA expression profiles between CDDP sensitive and resistant TGCT cell lines. By analyzing the obtained data, we will identify candidate mRNAs and miRNAs. After their verification, we will validate their function in CDDP resistance in TGCT patients. We will analyze their epigenetic regulation via methylation of their promoters, as well as determine differences in expression of the corresponding proteins. For this purpose, we will use TGCT cell lines and patient samples. Since we have recently found that the level of endogenous DNA damage represents a significant prognostic value in TGCTs, we will correlate endogenous DNA damage levels with genome instability in TGCT patients. We will also examine a role of the XPA protein in CDDP response, because our preliminary data shows that the level of this protein is also a significant prognostic factor in TGCTs. Using specifically designed XPA inhibitors, we will dissect selected functions of XPA and identify that its function that plays a role in CDDP response in TGCTs. We will also verify the role of promoter methylation, hypoxia, and alternative/aberrant mRNA splicing in regulation of the XPA protein level. Finally, we will clarify the relationship between the XPA, HMGB1 and HMGB4 protein levels in prognosis of TGCT patients.
Duration:	1.8.2018 - 30.6.2021

Effect of electrical stimulation on regeneration of injured neural pathways.
Účinok elektrickej stimulácie na regeneráciu poškodených nervových dráh.
Program:	VEGA
Project leader:	RNDr. Gálik Ján CSc.
Annotation:	Despite intensive efforts of researchers and clinicians, there is no, so far, an effective therapy for the recovery of nervous tissue after ischemic or traumatic injury. None of the few clinically approved procedures leads to satisfactory results. The aim of proposed project is to increase the effectiveness of current therapies by combining them with sustained electrical stimulation of injured tissue, which can facilitate regeneration of axons and provide guidance for their growth. We will test the possible synergistic effect of sustained stimulation with surgical, pharmacological and physical interventions.
Duration:	1.1.2020 - 31.12.2023

Virulence factors of tick-borne encephalitis virus and their role in transmission via tick vector
Úloha faktorov virulencie vírusu kliešťavej encefalitídy v prenose kliešťami
Program:	VEGA
Project leader:	RNDr. Koči Juraj PhD.
Annotation:	Tick-borne encephalitis virus (TBEV) causes one of the most severe neurodegenerative disorders transmitted by ticks. So far, studies on disease pathogenesis have focused primarily on a host and there is very little information on interactions between the virus and its vector although they are integral part of an enzootic cycle of the virus. Therefore, this proposal is focused to analyse interactions between TBEV strain Hypr and a tick Ixodes ricinus. By using a reverse genetics approach, viruses with a mutated domain III of protein E and incorporated reporter gene will be developed. Dynamics of transfer and interaction of recombinant viruses with ticks will be investigated using in vitro tick feeding system. Obtained results and developed tools will provide invaluable information on virus virulence factors and their role in establishing infection, dissemination and transfer within ticks. In addition, our studies will significantly contribute to research of other tick-borne viruses.
Duration:	1.1.2019 - 31.12.2022

The role of mitochondria in progression of colorectal cancer
Úloha mitochondrií v progresii kolorektálneho karcinómu
Program:	VEGA
Project leader:	RNDr. Tyčiaková Silvia PhD.
Annotation:	Mitochondria respond to energetic needs and stress stimuli by adapting their structure and function. Their morphology is changed in process of fusion and fission. Tumor cells maintain reprogrammed energetic metabolism towards aerobic glycolysis, display smaller mitochondria and activated dynamin-related protein 1, responsible for mitochondrial fission. Bioenergetic function of mitochondria is usually supressed in tumors. Our preliminary study shown that pro-apoptotic effect of drugs includes enhanced mitochondrial fission in colorectal cancer (CRC) cells. We suppose that mitochondrial morphology and size, changed by fusion and fission affects progression and invasivity of tumor cells. Therefore, we aim to study correlation among mitochondrial fission, status and aggressive phenotype of CRC-derived cells. We will examine the effect of Drp1 knockdown on mitochondria as well as the effect of overexpression of proteins responsible for mitochondrial fusion MFN1/2 in CRC cells in comparison to healthy cells.
Duration:	1.1.2021 - 31.12.2024

The role of neuroendocrine factors of stress response in the regulation of immune system activity in mammals
Úloha neuroendokrinných faktorov stresovej odpovede v regulácii aktivity imunitného systému cicavcov
Program:	VEGA
Project leader:	Ing. Vargovič Peter PhD.
Annotation:	Stress is one of the major factors affecting immune system. Sympathoadrenal and hypothalamus-pituitary-adrenocortical systems play a primary role in the stress response regulation and exhibit significant immunomodulatory effects. The aim of the project is to describe neuroendocrine regulation of immune cells in the spleen and thymus of mammals. We will evaluate effects of short and long-term stress on the development, differentiation, polarization and function of different types of leukocytes (macrophages, lymphocytes, granulocytes) during basal conditions or after induction of acute or chronic inflammation. We will characterize the immunomodulatory effects of the key stress mediators such like catecholamines, glucocorticoids and other hormones using experimental models with blocked central/peripheral stress response regulation, or by agonists/antagonists of receptors involved in the stress response. The acquired knowledge may help to understand the relationship between stress and immune diseases/disorders.
Duration:	1.1.2018 - 31.12.2021

Role of protein kinases in processes involved in maintenance of genome stability
Úloha proteínkináz v procesoch zúčastnených udržiavania stability genómu
Program:	VEGA
Project leader:	Ing. Čipák Ľuboš PhD.
Annotation:	Deregulation of proteins involved in processes of maintenance of genome stability leads to increased frequency of mutations and missegregation of chromosomes, which are commonly observed in cancer. Our project is aimed at a detailed analysis of the regulatory roles of protein kinases of the fission yeast Schizosaccharomyces pombe in processes involved in maintenance of genome integrity. We will focus on understanding of the regulatory mechanisms of phosphorylation of proteins which are involved in processes of chromosome segregation, RNA biogenesis, metabolism of heterochromatin and DNA repair. As these processes are linked and cross communicate with each other´s, deciphering the molecular mechanisms of their post-translational regulations will bring more light into the fundamental principles how these processes maintain the stability of genome.
Duration:	1.1.2018 - 31.12.2021

Role of the hydrogen sulfide in remodelation cytoskeleton in colorectal carcinoma cells; impact on activity of taxanes
Úloha sirovodíka pri remodelácií cytoskeletu v bunkách kolorektálneho karcinómu; vplyv na pôsobenie taxánov
Program:	Other projects
Project leader:	prof. Ing. Križanová Oľga DrSc.
Duration:	1.12.2019 - 31.12.2021

The role of urocortin 2 in the regulation of the stress response
Úloha urokortínu 2 v regulácii stresovej reakcie
Program:	VEGA
Project leader:	Ing. Tillinger Andrej PhD.
Annotation:	Stress response is one of the fundamental mechanisms for the organism survival in the case of threat. In addition to its positive role, stress can also play a negative role, especially when acting chronically or when the body is weakened by ongoing pathological processes. The HPA axis plays a crucial role in the regulation of stress response. Activity of this system is significantly modulated by CRH/urocortin group of proteins, which regulate the neuroendocrine and behavioral stress response. This group includes several proteins and one of them is urocortin 2. In present, the role of urocortin 2 in stress response is described only partially. However, its presence in the brain areas involved in stress response regulation, as well as its distribution in the periphery, indicate its involvement in mechanisms regulating the stress response. The aim of the proposed project is to clarify the role of urocortin 2 in the stress response and to describe regulation of its expression under stress conditions.
Duration:	1.1.2019 - 31.12.2021

Role of the calcium and calcium transport in tumorigenesis and tumor's treatment Key
Úloha vápnika a transportu vápnika v tumorigenéze a v liečbe nádorov
Program:	VEGA
Project leader:	prof. Ing. Križanová Oľga DrSc.
Duration:	1.1.2019 - 31.12.2021

Large-capacity cleaning of airborne pathogens
Veľkokapacitná čistička vzduchu od patogénov v aerosoloch
Program:	SRDA
Project leader:	MVDr. Kopáček Juraj DrSc.
Duration:	16.9.2020 - 31.12.2021

Effects of physical activity on psychological state of obese adolsecents
Vplyv fyzickej aktivity na psychiku u obéznych adolescentov
Program:	VEGA
Project leader:	doc. MUDr. Ukropcová Barbara PhD.
Duration:	1.1.2019 - 31.12.2022

Effect of haloperidol and olanzapine on the neurogenesis and apoptosis in schizophrenic model
Vplyv haloperidolu a olanzapínu na neurogenézu a apotózu v schizofrenickom modeli
Program:	VEGA
Project leader:	RNDr. Osacká Jana PhD.
Annotation:	Schizophrenia is a clinically heterogeneous psychiatric disease whose etiology has not been completely elucidated yet. The clinical, epidemiological, genetic, and neuropathological studies indicate that important role in its pathology may play abnormal alterations not only in the various neurotramsmitter systems (predominantly dopaminergic and glutamatergic) but also neurogenesis and apoptopic abnormalities in the relevant brain structures. Predominantly in the hippocampus of schizophrenic patients alterations in the expression of proteins playing important role in the neurogenesis and apoptosis processes, have been observed. The aim of the submitted project is to reveal the impact of clinically as well as generationally differently acting antipsychotics (drugs used in the schizophrenia therapy), i.e. an incizive first generation antipsychotic haloperidol and atypically acting olanzapine, on the neurogenesis and apoptosis in vitro and in vivo in pharmacologically induced model of schizophrenia.
Duration:	1.1.2019 - 31.12.2021

Effect of combinaion therapy with carnosine on tumorigenesis in colorectal carcinoma models
Vplyv kombinovanej terapie s karnozínom na proces tumorigenézy v modeloch kolorektálneho karcinómu
Program:	VEGA
Project leader:	RNDr. Baráthová Monika PhD.
Annotation:	Continuous search for new approaches and treatment strategies is essential in the treatment of cancer. Multiple drug combination therapy simultaneously involves several cellular mechanisms in order to make treatment more effective, reduce toxicity and prolong patient life. New therapeutic approaches use not only the combination of anticancer drugs but also natural substances. By ccombination therapy with carnosine and chemotherapeutic agents we want to affect mitochondrial mechanisms - bioenergetics, quenching of active forms of oxygen, indirectly also stability of HIF1a subunit, and use the impact of carnosine on pH regulation in tumor cells expressing CA IX. Together with chemotherapeutics, we want to analyze the impact of such combinations on proliferation, migration, metastatic potential as well as on the chemotherapy-resistant cancer stem cell pathways. The aim of the project is also to use 3D models of cell cultivation in spheroids and to introduce a method of forming microtumors from clinical samples.
Duration:	1.1.2020 - 31.12.2023

Impact of comorbidity therapy on tumorigenesis and a role of the tumor microenvironment in this process
Vplyv liečby komorbidít na tumorigenézu a úloha nádorového mikroprostredia v tomto procese
Program:	SRDA
Project leader:	RNDr. Baráthová Monika PhD.
Annotation:	The project is aimed at elucidation of potential connections among comorbidity therapy, various components of tumor microenvironment and tumorigenesis. Mutual interactions between microenvironmental factors point to its high complexity and organization. Thus, for true understanding of processes which affect neoplastic transformation, proliferation, invasion and metastazing as well as tumor cells response to therapy it is crucial to understand not onlly its components, but also their cross-talk. It becomes apparent that when selecting a suitable anti-tumor therapeutical strategy an overall condition of a patient must be taken into account, including chronically treated comorbidities. As cardiovascular system diseases treated by beta-blockers represent one of the most frequent comorbidities, we want to focus on the impact of chronic treatment with beta blockers on chemotherapy efficiency. The project implementation will also include the study of protein-protein interactions depending on changing tumor microenvironment comprising hypoxia, acidosis and influence of stress hormones. We will concentrate especially on tumor-associated carbonic anhydrase IX and functionally related proteins. Two-dimensional cell culture do not sufficiently mimic cell heterogeneity in tumor mass, gradients of nutrients, oxygen, pH or interactions with and composition of matrix. In this project we will focus on the development of 3D system of co-cultures of tumor epithelial cells with stromal components that would become a suitable model for the analysis of the impact of comorbidity therapy of tumorigenesis. Moreover, we want to clarify a possible link between comorbidity therapy and efficiency of standard chemotherapy. The integral part of the project will be the analysis of retrospective and prospective samples from primary patients tumors, subjected to appropriate stratification, which will allow profiling of cells obtained from different stages of tumorigenesis.
Duration:	1.7.2017 - 30.6.2021

Influence of NS1 protein and influenza virus load on the pathogenesis and innate immune response in brains, hearts and spleens of infected mice
Vplyv proteínu NS1 a infekčnej dávky vírusu chrípky na patogenitu a vrodenú imunitnú odpoveď v mozgoch, srdciach a slezinách infikovaných myší
Program:	VEGA
Project leader:	doc. RNDr. Betáková Tatiana DrSc.
Annotation:	Despite the widespread application of vaccination programs, influenza viruses are still among the most harmful human pathogens. Influenza encephalopathies, encephalitis lethargica and Reye´s syndrome are rare, but serious diseases that manifest with influenza infection. High pathogenic strains are able to spread to the brain, liver and other organs. NS1 protein counteracts the induction of antiviral response. Our preliminary data shows, that the immune response was activated in the brain and spleen of mice infected with low pathogenic influenza virus despite of fact that virus was not detected in these organs. The main aim of this project is to investigate the influence of virus pathogenicity as well as NS1 protein on the spread of the virus into the brain, heart and spleen of infected mice and on their ability induce RIG-1-like receptor signaling pathway in these organs. We also suggest that the cells of immune system like macrophages, neutrophils, etc. play more important role in pathogenesis.
Duration:	1.1.2020 - 31.12.2023

Centre of Excellence for advanced materials application
Vybudovanie Centra pre využitie pokročilých materiálov Slovenskej akadémie vied
Program:	EU Structural Funds Research & Development
Project leader:	RNDr. Csáderová Lucia PhD.
Duration:	1.7.2019 - 30.6.2023

Investigation of the Host – Parasite, Cell - Rickettsia Relationship, Monitored by Transcriptomic and Proteome Studies.
Výskum hostiteľsko – parazitických, bunkovo - Rickettsiových vzťahov, monitorovaných pomocou transcriptomických a proteomických štúdií.
Program:	SRDA
Project leader:	RNDr. Sekeyová Zuzana PhD.
Annotation:	In recent years, the host – parasite relationship is increasingly monitored by transcriptomic and proteome studies. It is obvious, that host–pathogen interactions involves protein expression changes in both actors the host cells and the rickettsial pathogen. An understanding of the nature of these interactions at the proteomic level will provide insight into metabolic processes, critical regulatory events of the host cells as well as the mechanism of pathogenesis of rickettsioses. We aim to study these regulatory events, control mechanisms, which underlie not only the functioning of individual cells but also the processes of differentiation and development, protein synthesis, processing, folding or degradation, both in infected cells and Rickettsiae. We will use premium, the state-of-the-art proteomic technologies enabling of measuring several thousands of proteins within a few hours, they will permit us to significantly increase the analytical depth as well as coverage in complex proteome analyses. We will be interested in the function of proteins with respect to the course of protein expression at which can be regulated the flow of information from the genome to the Proteome, in both Rickettsiae and the infected cells. We aim to search for transcriptional changes in infected cells observed following exposure to Rickettsiae and to a nutrient stress that will be verified, starting from amplified cDNA and total RNA as templates, means we will apply an approach that has great potential for the study of mechanisms behind the virulence and intracellular survival of members of the genus Rickettsia.
Duration:	1.7.2020 - 30.6.2024

Research of humanized antibodies in targeted treatment of hypoxic tumors
Výskum humanizovaných protilátok v cielenej liečbe hypoxických nádorov
Program:	Other projects
Project leader:	prof. RNDr. Pastoreková Silvia DrSc.
Duration:	1.12.2018 - 1.12.2021

Immune response to SARS-CoV-2 infection and development of clinically relevant virological tests to improve the management of the COVID-19 pandemic
Výskum imunitnej odpovede na infekciu SARS-CoV-2 a vývoj klinicky relevantných virologických testov na zvládnutie dopadov pandémie COVID-19
Program:	SRDA
Project leader:	RNDr. Klempa Boris DrSc.
Annotation:	COVID-19 pandemic is an unprecedented situation which the world as well as Slovakia have not faced in its modern history. One of the key prerequisites for mitigation of its negative societal impact is to better understand human immune response to the SARS-CoV-2 and to introduce effective diagnostic procedures improving patients ́ management and disease control. In this project, institutions actively contributing to the COVID-19 control in Slovakia joined forces in order to address specific clinical, diagnostic, and epidemiologic needs which arose during the first wave of the pandemic in Slovakia. Main objective of the project is to improve our knowledge on immune response to SARS-CoV-2 infection through systematic analyses of a series of clinical specimens from the defined cohorts of study participants with the battery of defined immunological and virological assays. The obtained data will be used for development of mathematical models of the immune response on individual level and of the virus spread within the population in order to identify most important risk factors influencing the epidemiologic situation in Slovakia. Essential part of the project will be development of virological techniques which require handling of infectious virus in the biosafety level 3 laboratory such as virus neutralization test or virus isolation. These methods will be directly available for the clinical practice. There is also an urgent need to develop a set of assays for verification of non-infectivity of the long-term viral-RNA positive patients. Important ambition of the project is also an improvement of the primary diagnostics through combination of saliva as a diagnostic fluid with the loop-mediated isothermal amplification (LAMP) method. Unique interdisciplinary collaboration of partners with expertise in virology, molecular biology, immunology, clinical infectology and mathematical modeling warrant originality and success of this project.
Duration:	16.9.2020 - 31.12.2021

Occurrence and variability of economically important crop viruses under greenhouse conditions in Slovakia and analysis of epidemiological factors affecting their virulence and spread
Výskyt a variabilita vírusov hospodársky významných plodín v skleníkových podmienkach na Slovensku a analýza epidemiologických faktorov ovplyvňujúcich ich virulenciu a šírenie
Program:	VEGA
Project leader:	Mgr. Predajňa Lukáš PhD.
Duration:	1.1.2018 - 31.12.2021

Utilization of the calcium transport blockers as potential chemotherapeutics in a treatment of solid tumors
Využitie blokátorov vápnikových transportérov ako potecionálne chemoterapeutiká pri liečbe solidných tumorov
Program:	SRDA
Project leader:	prof. Ing. Križanová Oľga DrSc.
Duration:	1.7.2017 - 30.6.2021

Harnessing the immunological mechanisms in various subtypes of B cell lymphoma
Využitie imunologických mechanizmov v rôznych subtypoch B-bunkových lymfómov
Program:	SRDA
Project leader:	RNDr. Cholujová Dana PhD.
Annotation:	Malignant lymphomas are mostly incurable blood cancers affecting different white blood cells formed in lymphoid structures, including the lymph nodes, spleen, and bone marrow. They have different origin in B cell development with different biological properties and clinical aggressiveness. This tumor cells compete for space to grow within tumor microenvironment by affecting the surrounding healthy cells in the bone marrow to suppress patient immunity. The purpose of this proposal is to better understand tumor and tumor-driven immune changes and evaluate their phenotypic differences and functional complexity by comprehensive state-of-art technology mass cytometry (CyTOF). Furthermore, we will study the immunological mechanisms “immune checkpoints” that can be targeted in malignant lymphoma. The better understanding of pathogenesis of B-cell malignancies will lead to new therapeutic strategies directed against tumor and immune cells to completely eradicate tumor in individual patient.
Duration:	1.7.2020 - 30.6.2024

The application of myrosinase for sulforaphane activation in development of a novel product exhibiting cancer prevention effects
Využitie myrozinázy na aktiváciu sulforafanu pre vývoj preparátu s preventívnymi účinkami nádorových ochorení
Program:	SRDA
Project leader:	RNDr. Sedlák Ján DrSc.
Annotation:	Effects of sulphoraphane on cancer prevention was already proven. Sulforaphane is often presents in food at the non-effctive level for fulfillment the prevention effects. In addition, the natural glucosinolate form of sulforaphane, glucorafanine, is much less effective, therefore its activation to sulforaphane is needed. This conversion is catalysed by enzyme, myrosinase (EC 3.2.1.147). Aim of the current project is to design the new product based on sulforaphane-glucosinolate and stabilized myrosinase as combine product.
Duration:	1.7.2017 - 30.6.2021

Regulation of Angiotensin II receptors in neuroprotection after traumatic spinal cord injury
Využitie regulácie angiotenzínových receptorov v neuroprotekcii po traumatickom poranení miechy
Program:	VEGA
Project leader:	RNDr. Pavel Jaroslav PhD.
Duration:	1.1.2019 - 31.12.2021

Development of 3D co-culture systems integrating several components of tumor microenvironment and study of their influence on the course of anti-tumor therapy
Vývoj 3D ko-kultivačných systémov integrujúcich jednotlivé zložky nádorového mikroprostredia a sledovanie ich vplyvu na priebeh protinádorovej terapie.
Program:	VEGA
Project leader:	RNDr. Csáderová Lucia PhD.
Duration:	1.1.2018 - 31.12.2021

Development and testing of molecular and informatic tools for effective characterisation and interpretation of clinically relevant microsatellite repetitive motifs from genomic data
Vývoj a testovanie molekulárnych a informatických metód na efektívnu charakterizáciu a interpretáciu klinicky relevantných mikrosatelitových repetitívnych motívov z genomických dát
Program:	SRDA
Project leader:	RNDr. Radvánszky Ján PhD.
Annotation:	The proposed project is based on the recognition of facts that: (i) the genomic material of each person contains an immense amount of health-related information; ii) the usability of these genomic information depends on our ability to identify genomic variants; iii) microsatellite motifs (STRs) play an important role in various aspects of physiological and pathological processes of our organisms. Despite that STRs represent the most variable loci of our genome, their variability is still very poorly described. In particular this is caused by a lack of tools allowing their accurate and comprehensive evaluation from large-scale genomic data sets. The aim of our project is, therefore, to examine specific aspects of possibilities of STR motifs characterisation from whole-genome sequence data with simultaneous development and validation of molecular-genetic approaches and bioinformatics tool capable of processing data derived from massively parallel sequencing. From these data thedeveloped tool should be able to extract clinically relevant information, such as the numbers and exact sequence of repetitions of particular alleles, the phase of individual parts of complex motifs, signs of motif instability, and the presence of possible pathological expansions of repeat numbers. As a clinical model we chose two main patient groups: 1) patients with a molecularly confirmed diagnosis of disease caused by expansions of STR motifs (myotonic dystrophy type 1 and 2, Huntington's disease and Fragile X syndrome); 2) patients with Lynch syndrome, in whom instability of microsatellite motif is an important clinical biomarker. Based on the generated data as well as on data derived from appropriate conventional validation methods and other already available tools, we plan to perform comprehensive statistical validation and characterization of the reliability, accuracy and practical applicability of our newly developed tool in specific areas of biomedicine and personalized healthcare.
Duration:	1.7.2019 - 30.6.2023

Development of novel diagnostic and predictive high-dimensional immunophenotyping tool for hematological malignancies
Vývoj nového diagnostického a prediktívneho vysokodimenzionálneho imunofenotypizačného nástroja pre hematologické malignity
Program:	Other projects
Project leader:	RNDr. Jakubíková Jana PhD.
Annotation:	Immunophenotyping is currently one of the fundamental pillars for the diagnosis, classification, staging and monitoring of hematological malignancies, such as leukemia and lymphoma. In this study, we will take an advantage of novel high-dimensional technology mass cytometry that to develop novel diagnostic and predictive approach with complex multi-dimensional immunophenotyping profiles and overall immune cell profiling to diagnose, classify, stage and monitor of the therapy response in patients with leukemia, lymphoma and multiple myeloma.
Duration:	1.11.2019 - 31.12.2021

The development of translationally relevant regenerative and reparative strategies after spinal cord trauma
Vývoj translačne relevantných regeneračných a reparatívnych stratégií po traumatickom poranení miechy
Program:	SRDA
Project leader:	RNDr. Lukáčová Nadežda DrSc.
Annotation:	The aim of this project is to investigate the regulatory impact of clinically approved/tested anti-inflammatory drugs on the polarization of M1/M2 macrophages, which play a key role in activation of pro-regenerative molecules following traumatic spinal cord injury and design translational strategies that have the potential to improve functional recovery of experimental animals. We propose to examine the protein profile of selected spinal cord regions (lesion site, above and below the site of injury) after Th9 compression and application of methylprednisolone, atorvastatin, siponimod and VX-210 in acute/subacute phase of spinal injury, and evaluate their neuroprotective potential. We intend to develop a new technology that allows local application of the most effective drug with a gradual, time-dependent release to the site of spinal cord lesion. We suggest, that drug with the most efficient anti-inflammatory and antioxidant effect in combination with VX-210 (an inhibitor of Rho activity) locally administered via magnetic nanoparticles, will make the spinal treatment more effective and support the regenerative potential of nerve tissue. We plan to stimulate the functional recovery of motor and sensory functions by physical rehabilitation and long-term application of a weak electric field at the lesion site. The neuroprotective effect of synergic action of proposed approaches will be evaluated by analyzes of the expression of pro-regenerative signal molecules, axonal outgrowth, inter-neuronal and neuromuscular junctions and functional recovery.
Duration:	1.7.2020 - 30.6.2024

Developing a high-throughput, sensitive RT -qPCR test and rapid, point-of-care RT-LAMP test for the differentiation of SARS-Cov-2 and influenza
Vývoj vysoko výkonného, citlivého RT-qPCR testu a rýchleho RT-LAMP testu na rozlíšenie SARS-CoV-2 a chrípky
Program:	SRDA
Project leader:	RNDr. Klempa Boris DrSc.
Duration:	16.9.2020 - 31.12.2021

The significance of the interaction between scaffolding proteins and subcellular organelles in neuronal cells: the role of oxytocin
Význam interakcie skafoldových proteínov so subcelulárnymi organelami v neuronálnych bunkách: úloha oxytocínu
Program:	VEGA
Project leader:	doc. RNDr. Bakoš Ján PhD.
Annotation:	The origin, etiology and potential therapeutic approaches of neurodevelopmental disorders include genetic, molecular and pathophysiological aspects. The failure in oxytocin receptor signaling during the specific stages of the brain development is increasingly suspected as a cause of deficit in neuritogenesis, synaptogenesis and neuron connectivity. The explanation of these processes requires complex technical approaches allowing evaluation of the cytoskeletal proteins connecting neuronal cell membrane with the vesicular apparatus of the endoplasmic reticulum. The aim of the project is to clarify the role of oxytocin in the regulation of scaffolding proteins connecting to the endoplasmic reticulum in neuronal cells. The analysis of the expression of the SHANK family proteins, their visualization and co-localization with the subcellular organelles will be performed. Our understanding of the oxytocin action on the neuronal cell structure can contribute to the intervention in neurodevelopmental disorders.
Duration:	1.1.2020 - 31.12.2022

Assessment of immune checkpoints in B cell malignancies
Zhodnotenie imunitných kontrolných bodov v B-bunkových malignitách
Program:	VEGA
Project leader:	RNDr. Cholujová Dana PhD.
Annotation:	Cancer immunotherapy is the idea of boosting the tumor-specific adaptive immune response instead of directlytargeting cancer cells. However, cancer cells can avoid immune surveillance by suppressing immunity throughactivation of specific inhibitory signaling pathways, referred to as immune checkpoints. Recently, the blockade ofcheckpoint molecules such as PD-1, PD-L1 and CTLA-4, with monoclonal antibodies targeting these checkpointmolecules has enabled the development of breakthrough therapies in oncology, with ongoing preclinical andclinical trial in B-cell malignancies. The overall objective of this proposal is to study B cell malignancies focusingon immune checkpoints molecules either in clonal tumor or immune accessory populations of tumormicroenvironment. Moreover, we will evaluate the effect of immune checkpoints neutralizing antibodies eitheralone or in combination (also with novel immunomodulatory drugs) to increase their efficacy as potential therapyfor patients with B-cell malignancy.
Duration:	1.1.2020 - 31.12.2022

Hepatic, lipid and cardiometabolic parameters changes in obese patients
Zmeny hepatálnych, lipidových a kardiometabolických parametrov u pacientov s obezitou
Program:	VEGA
Project leader:	MUDr. Penesová Adela PhD.
Annotation:	Morbid obesity (MO, BMI >40 kg/m2) represents 2-3 times higher risk of diabetes, dyslipidemia, cardiovascular (CVS) diseases and non-alcoholic fatty liver disease (NAFLD). Our hypothesis is that even 10% reduction of body weight in MO will lead to improvement of liver parameters, hepatokines, LDL and HDL subfraction of lipoproteins, insulin sensitivity as well as to decrease of CVS risk. The aim of our study is to monitor the effect of intensive life style changes in MO patients and super morbid obesity (SO, BMI >50 kg/m2) on aforementioned parameters during 12 months. We have more than 270 obese, 23 MO and 28 SO patients in our registry. Intervention of life style will be individualized; dominant will be either physical activity and/or diet. Evaluation of hepatokines and lipid subfractions and analysis of anthropometry changes will contribute to understanding and extending the knowledge about the possibilities how to reverse the onset of NAFLD and KVS risk factors in MO and SO patients.
Duration:	1.1.2020 - 31.12.2023

The total number of projects: 129