Information Page of SAS Organisation

Biomedical Research Center SAS

International projects

Alliance4Life - Life Science Alliance: Closing Research and Innovation Divide in the EU
Aliancia pre živé vedy: zmenšovanie výskumnej a inovačnej prepasti v Európskej únii
Program: Horizont 2020
Project leader: prof. RNDr. Pastoreková Silvia DrSc.
Duration: 1.1.2018 - 31.12.2019

CAPSID - Scientific capacity building in biomedical research through scientific exchange and co-development of research services
Budovanie vedeckých kapacít v biomedicínskom výskume prostredníctvom vedeckej výmeny a spoločného rozvoja výskumných služieb
Program: European Regional Development Fund (ERDF)
Project leader: Mgr. Nemčovičová Ivana PhD.
Annotation:The central aim of the project is to strengthen regional capacities and improve international reputation in the field of biomedical research. The joint development of state-of-the-art working processes and the emergence of a new protein acquisition platform for biomedical purposes are, among other things, to lay the foundations for the long-term cooperation of the participating institutions. Collaboration in the field of expertise between the Vienna Biocenter and the Biomedical Research Center of the Slovak Academy of Sciences will enable project CAPSID to develop new scientific services for the acquisition of proteins for biomedical research purposes. These highly specialized production and cleaning processes meet growing demand as well as increasing demand for high quality. Protein retrieval methods will be available through a new service platform. While implementing new methods, many students will be trained and the online platform will serve to exchange research outputs. Particular emphasis will be placed on international cooperation and intensive communication: conferences and workshops will be a meeting place for international scientists, experts from universities, research institutes and biotechnology companies that reside in a cross-border region.
Project web page:https://capsid.vbcf.ac.at/
Duration: 1.7.2018 - 31.12.2021

TACTiCAl - Targeted combination therapy of colon cancer with therapeutic gene/drug loaded novel dendritic nanocarriers
Cielená kombinovaná terapia nádoru hrubého čreva pomocou rozvetvených nanonosičov nesúcich terapeutický gén a liečivá
Program: Bilaterálne - iné
Project leader: RNDr. Matúšková Miroslava PhD.
Annotation:Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths in the world, and prognosis remains dismal for patients with metastatic disease. Significant portion of early-stage patients develop recurrence after chemotherapy. There is a need for novel therapeutic approaches. Multifunctional nanocarriers enable targeted co-delivery of drugs and genes, while maintaining their chemo-physical properties and biological functions. Dendritic polymers possess controllable structure with a large population of terminal functional groups, low solution or melt viscosity, and good solubility. These properties allow their use in numerous bioapplications, including their application in targeted anti-tumour therapies. To increase the efficacy of conventional CRC treatment and to overcome drug resistance, we aim to develop multimodal nanotherapeutic system, for targeted delivery of multifunctional combinational therapy. Polyamidoamine - based dendrimers will be used to carry: cytotoxic drug 5-fluorouracil (5FU), plasmid containing apoptosis-mediating TRAIL gene, chemosensitising epigenetic agent suberoylanilide hydroxamic acid (SAHA), selective targeting moiety (folate molecules) and imaging agent. The safety and efficacy of the newly constructed dendritic molecules loaded with therapeutics will be evaluated. Nanocarriers will be synthesized and characterized by Genetic Engineering and Biotechnology Institute of TUBITAK Marmara Research Center. The biological effects will be assessed at Biomedical Research Center of Slovak Academy of Sciences. Therapeutic efficiency, potential toxicity, biodistribution, bioavailability, bioelimination, and release of therapeutics will be studied on CRC pre-clinical in vitro and in vivo models.
Duration: 3.9.2018 - 30.9.2021

rickdet - Detection and Characterization of Rickettsiae and Similar Microorganisms.
Detekcia a charakterizácia Rickettsií a im podobných mikroorganizmov
Program: Bilaterálne - iné
Project leader: RNDr. Sekeyová Zuzana PhD.
Annotation:Aims and results shared in this project will provide a number of theoretical knowledge in the field of molecular analysis of rickettsiae and a like microorganisms, with similar direct intrusions into medical practice, means such interferences that will predict and affect an analytical accuracy of diagnoses of rickettsioses, and similar, biologically active intracellular bacteria. We will provide a specific picture of the course of the diseases caused by them, and will try to transfer this knowledge to determination of the specific laboratory indicators of studied pathogens at the molecular level. Reliable diagnoses, vigilance, preparedness, and the availability of efficacious vaccines and antibiotics are dependent on assignation of precise biomarkers that will enhance diagnostic capabilities and reduce delayed identification or misdiagnosis of infectious agent.
Project web page:http://www.apvv.sk/buxus/docs/vyzvy/bilateralne/sk-fr-2017/vysledky/vyzva-sk-fr-2017-rozhodnutie.pdf ; http://www.apvv.sk/grantove-schemy/bilateralne-vyzvy/slovensko-francuzsko-2017.html ; https://institutfrancais.sk/fr/sciences-univ/phc-stefanik/
Duration: 1.1.2018 - 31.12.2019

COST-ENBA - European Network of Bioadhesion Expertise: Fundamental Knowledge to Inspire Advanced Bonding Technologies
Drosophila salivary gland secretory proteins as tunable and biodegradable natural glue
Program: COST
Project leader: RNDr. Farkaš Robert CSc.
Duration: 1.1.2017 - 31.12.2020

CellFit - In vitro 3-D total cell guidance and fitness
In vitro 3-D bunkové modely – metodické postupy a ich relevantnosť
Program: COST
Project leader: RNDr. Šramková Monika PhD.
Annotation:The present Action is aimed at refining our understanding of the in vivo microenvironment, reducing the differences when translating it in vitro, to create 3D total guidance ex vivo culture systems for the replacement of animal use. Traditional in vitro 2D culture systems fail to imitate the physiological and biochemical features of cells in the original tissue. Differences between the microenvironment provided by cell culture models and that distinct of the in vivo tissues are significant and can cause deviations in cell response and behaviour. In this COST Action, the present understanding of in vivo micro/macro-environment will be refined in order to reproduce in vitro the physiological system in the best possible way: surface topography, substrate stiffness, mechanical stimulation, chemical cues and localised density will be analysed. This will allow to develop reliable “3D total guidance” in vitro models reducing the number of animals used and allowing a safe translation of the present basic knowledge in cell repair and regeneration from the laboratory bench to the clinical application, with a positive impact on every day’s life patients and general Health costs.
Project web page:http://cost-cellfit.eu/
Duration: 16.3.2017 - 15.3.2021

INNOCENT - Innovative Nanopharmaceuticals: Targeting Breast Cancer Stem Cells by a Novel Combination of Epigenetic and Anticancer Drugs with Gene Therapy
Inovatívne nanoliečivá: Nová kombinácia epigentických a protinádorových liečiv s génovou terapiou zacielená voči nádorovým kmeňovým bunkám karcinómu prsníka
Program: ERANET
Project leader: Mgr. Smolková Božena PhD.
Annotation:The aim of the INNOCENT project is to develop innovative multifunctional nanopharmaceuticals to overcome the low efficacy and frequent relapses in breast cancer (BC) treatment, with emphasis on cancer stem cells (CSCs). The proposed multimodal COMBOBOMB, brilliantly integrates the diagnostic and therapeutic functions within a single nanostructure. The COMBOBOMB harbours four major components: 1) a selective targeting moiety (chitosan-targeted CD44); 2) a diagnostic imaging aid for localization of the malignant tumour and its micro- or macrometastases (inorganic nanocrystals); 3) a cytotoxic drug (doxorubicin), and 4) a chemosensitising agent (decitabine, DAC along with DAC-activating enzyme) utilising gene therapy and epigenetic approaches.
Project web page:http://www.innocent.sav.sk/index.html
Duration: 1.1.2017 - 31.12.2019

iPAAC - INNOVATIVE PARTNERSHIP FOR ACTION AGAINST CANCER
Inovatívne partnerstvo pre boj proti rakovine (Spoločná aktivita podporená Európskou komisiou v rámci tretieho programu v oblasti zdravia)
Program: Iné
Project leader: prof. RNDr. Pastoreková Silvia DrSc.
Project web page:www.ipaac.eu
Duration: 1.4.2018 - 31.3.2021

hCOMET - The Comet assay as a human biomonitoring tool
Kométový test ako nástroj na biologické monitorovanie ľudí
Program: COST
Project leader: RNDr. Gábelová Alena CSc.
Annotation:Many human biomonitoring studies have used the comet assay to measure DNA damage (some also measuring DNA repair). In most cases, the assay is applied to peripheral blood mononuclear cells. Results from relatively small individual studies are often inconsistent, and it is advantageous to carry out a pooled analysis of the combined data from all available studies. hCOMET will be a network comprising researchers who are active (or intend to be active) in human biomonitoring with this assay. Results supplied by these researchers will be compiled as a single database representing an estimated 19,000 individual DNA damage measurements. The pooled analysis will allow us to determine which factors (smoking, age, nutrition, sex, occupational exposure etc.) affect DNA damage, and to what extent. Fewer studies have included DNA repair capacity as an endpoint; we will collect what data we can and carry out a detailed review (or a pooled analysis if enough data). In addition, hCOMET will address the issue of inter-laboratory reproducibility of the assay by devising standard protocols, for both DNA damage and DNA repair measurement, coordinating ring studies to test these protocols, and offering training courses and exchanges, so that in future comparison of results from different studies will be facilitated. We will review applications of the assay to other human cell types and isolation methods (such as leukocytes obtained from frozen blood).
Duration: 1.4.2016 - 31.3.2020

High-field MRS, a tool to estimate the tissue-specific metabolic state reflecting thyroid hormone activity in vivo: validation of the “virtual biopsy” clinical relevance
Magnetická rezonančná spektroskopia ako nástroj na sledovanie tkanivovo-špecifického metabolických parametrov, ktoré sa spájajú s účinkami tyroidálnych hormónov in vivo: overenie klinickej relevantnosti takejto “vitruálnej biopsie”
Program: Bilaterálne - iné
Project leader: Mgr. Ukropec Jozef DrSc.
Duration: 1.1.2018 - 31.12.2019

Skeletal muscle metabolic abnormalities in patients with idiopathic inflammatory myopathies
Metabolické abnormality kostrového svalu u pacientov s idiopatickými zápalovými myopatiami
Program: Bilaterálne - iné
Project leader: doc. MUDr. Ukropcová Barbara PhD.
Duration: 1.4.2016 - 31.3.2020

Mitochondrial mapping: Evolution - Age - Gender - Lifestyle - Environment
MITO-EAGLE: Evolúcia-Vek-Pohlavie-Životný štýl-Prostredie
Program: COST
Project leader: Mgr. Ukropec Jozef DrSc.
Duration: 1.1.2017 - 1.9.2020

MEDBIODOSE - Molecular Markers for Biological Dosimetry in Radiation Oncology, Cancer Risk, Assesment and Optimizing Cancer Therapy
Molekulárne markery pre biologickú dozimetriu v radiačnej onkológii a hodnotenie rizika vzniku a optimalizácie liečby rakoviny
Program: IAEA
Project leader: doc. Ing. Beliaev Igor DrSc.
Annotation:Cytogenetic analysis remains the only standard method for biological dosimetry. It is generally accepted that new molecular markers associated with biological dosimetry and cancer risks should be established and dependence of these risks on conditions of irradiation such as dose should be verified. Relevant cellular model systems are needed to verify and predict these risks. Hematopoietic stem cells (HSC) are the major target of leukemogenesis and also most relevant cellular model for assessing cancer risk associated with ionizing radiation. Usually, characteristic chromosomal translocations resulting in so-called preleukemic fusion genes (PFG) arise prenatally in HSC as a first key event in multistage process of leukemogenesis. DNA double-strand breaks (DSB) are critical DNA damage resulting in PFG. CD34+ HSC stem cells from umbilical cord blood (UCB) will be studied in comparison to lymphocytes. The project will focus on the low dose range (≤10 cGy) to which people is usually exposed in aircrafts during flights, at security controls (airports) and during medical investigations (such as computer tomography and mammography). The data will be also obtained in higher dose range to find out whether the low dose effects can be extrapolated from the higher doses. This project will validate possible molecular markers for estimation of low-dose effects in HSC and lymphocytes which may be used in biodosimetry and cancer epidemiological studies. Possible correlation of constitutive and induced DNA damage and apoptosis will be analyzed in hematopoietic cells of ALL and AML patients. The obtained data will be correlated with immunophenotype, presence of PFG and clinical outcome such as treatment response, minimal residual disease (MRD), risk group, side effects. If some correlations will be established it may provide new strategy for optimizing cancer therapy.
Project web page:https://www.iaea.org/newscenter/news/new-crp-applications-of-biological-dosimetry-methods-in-radiation-oncology-nuclear-medicine-diagnostic-and-interventional-radiology-e35010
Duration: 19.9.2017 - 9.7.2021

NANO2CLINIC - Cancer Nanomedicine - from the bench to the bedside
Nanomedicína rakoviny - z laboratória k pacientovi
Program: COST
Project leader: RNDr. Šramková Monika PhD.
Duration: 28.9.2018 - 27.9.2022

Neuroprotective potential of cryopreserved placental mesenchymal stem cells (MSCs), extract, cord blood serum in the spinal cord injury (SCI).
Neuroprotektívny potenciál zamrazených mezenchýmových kmeňových buniek (MSCs) placenty, extraktov, séra pupočníkovej krvi pri poranení miechy (SCI).
Program: Medziakademická dohoda (MAD)
Project leader: RNDr. Slovinská Lucia PhD.
Annotation:Determine the neuroprotective potential of cryopreserved placental MSC, placental extract and cord blood serum with spinal cord injuries. Determine the neuroprotective potential of cryopreserved placental MSC, placental extract and cord blood serum with spinal cord injuries.
Duration: 1.1.2017 - 31.12.2019

New diagnostic and therapeutic tools against multidrug resistant tumors
Nové diagnostické a terapeutické nástroje v liečbe mnoholiekovej rezistencie nádorov
Program: COST
Project leader: RNDr. Jurkovičová Dana PhD.
Project web page:https://www.cost.eu/actions/CA17104/#tabs|Name:overview
Duration: 11.9.2018 - 10.9.2022

Role of the CA IX ectodomain in tumor growth and metastasis
Úloha ektodomény CA IX v nádorovom raste a metastázovaní
Program: Iné
Project leader: prof. RNDr. Pastoreková Silvia DrSc.
Annotation:This project is aimed at understanding the role of the CA IX ECD in tumor growth and metastasis in vivo using mouse models. We intend to evaluate growth of tumor xenografts (following subcutaneous implantation of tumor cells) and colonization of lungs (following injection of tumor cells into the tail vein) in absence and presence of the recombinant CA IX ECD. In addition, we plan to evaluate potential therapeutic targeting of CA IX ECD through analysis of the anticancer effect of antibodies binding to different regions of the ectodomain, including M75 and VII/20. Particularly M75 is of great interest, because the N-terminal PG region, to which M75 binds, was recently found to be involved in cell adhesion and spreading, the processes contributing to metastatic dissemination. On the other hand, MAb VII/20 binds to the central CA catalytic domain and was previously shown to reduce the growth of primary tumors, but its effect on metastasis has not been examined so far. Thus, we expect that the project will allow us to dissect the role of ECD in metastasis and propose antibody-based therapeutic strategies to reduce metastatic growth.
Duration: 11.11.2014 - 31.12.2019

Oxytocin role in the regulation of expression of GTPases in transgenic mouse model of neurodevelopmental disorder
Úloha oxytocínu v regulácii expresie GTPáz v transgénnom modeli neurovývinového ochorenia
Program: Bilaterálne - iné
Project leader: RNDr. Bakoš Ján PhD.
Annotation:Neurodevelopmental diseases, particularly Prader-Willi syndrome, Schaaf-Yang syndrome and spectrum of autism disorders may be associated with deficiencies in oxytocin system. Oxytocin, a known reproductive hormone, is considered to be a trophic and differentiating factor in the brain, however, there is a lack of studies on the manipulation of oxytocin system in relation to brain development. French team created a Magel2-knockout mouse model and showed that the mutant pups suffer from lack of sucking initiation right after birth (in males and females) and show autistic behavior in male adulthood. This model is widely accepted as a model of human Prader-Willi syndrome, in which Magel2 is deleted, and Schaaf-Yang syndrome, presenting point mutations of Magel2. The major aim of the present collaborative project is to contribute to clarification of the oxytocin effects on expression of GTPases in transgenic mouse model of neurodevelopmental disorder. Slovak research team together with French partners will closely collaborate to analyze GTPases and evaluate cytoskeletal proteins associated with neurite growth under oxytocin influence in Magel2-deficient mice. Studying the role of oxytocin in the process of early brain maturation and to measure its potential to compensate the neurodevelopmental deficits can bring relevant data for clinical and regenerative medicine.
Duration: 1.1.2018 - 31.12.2019

Monitoring of effects of natural and synthetic ligands of nuclear retinoid receptors on key proteins involved in epithelial-mesenchymal transition in human breast cancer cells by the mass spectrometry
Využitie hmotnostnej spektrometrie pre sledovanie vplyvu prirodzených a syntetických ligandov nukleárnych retinoidných receptorov na kľúčové proteíny epiteliálne-mezenchymálneho prechodu u buniek karcinómu prsníka
Program: Medziakademická dohoda (MAD)
Project leader: Ing. Brtko Július DrSc.
Duration: 1.1.2018 - 31.12.2020

Developing of innovative method of spinal cord injury effective treatment.
Vývoj inovatívnej metódy na efektívnu liečbu poškodenia miechy.
Program: Medziakademická dohoda (MAD)
Project leader: RNDr. Gálik Ján CSc.
Duration: 1.1.2017 - 31.12.2019


National projects

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Alternatívne zdroje kmeňových buniek pre regeneráciu poškodeného tkaniva CNS
Program: VEGA
Project leader: RNDr. Slovinská Lucia PhD.
Duration: 1.1.2019 - 31.12.2021

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

Expression analysis of miRNA genes regulating the biology of cancer stem cells in breast cancer patients
Analýza expresie génov pre miRNA regulujúcich biológiu nádorových kmeňových buniek u pacientok s karcinómom prsníka
Program: VEGA
Project leader: Mgr. Zmetáková Iveta PhD.
Annotation:The high mortality rate for malignant tumors, breast cancer included, is mainly due to their ability to metastasize. A key regulator of hematogenous metastasizing is the process of epithelial-mesenchymal transition (EMT), which allows the epithelial cells to acquire a mesenchymal phenotype and become circulating tumor cells (CTCs). Cancer stem cells (CSCs) are a subpopulation of CTCs, with acquired properties of stem cells responsible for tumor progression, metastases and relapse of cancer. MiRNAs are small non-coding RNAs, which regulate via various mechanisms the amount of physiological cell processes. The deregulation of their expression plays an important role in carcinogenesis. In the present project, we will analyze the expression of 84 miRNAs involved in the biology of CSCs in CTCs enriched population of peripheral blood cells in breast cancer patients. Our goal is to identify potentially clinically relevant miRNAs with possible use for monitoring the risk of metastasis development.
Duration: 1.1.2017 - 31.12.2020

STEMCELL - Investigation of potential and role of the central canal lining in the reaction to the spinal cord injury
Analýza potenciálu a úlohy výstelky centrálneho kanála pri regenerácii miechy po poranení
Program: APVV
Project leader: RNDr. Račeková Enikö CSc.
Duration: 1.7.2016 - 30.6.2020

Antioxidative, anticarcinogen and photoprotective effects of the essential oil from lavender in vitro.
Antioxidačné, antikarcinogénne a fotoprotektívne účinky levanduľového oleja in vitro.
Program: VEGA
Project leader: RNDr. Kozics Katarína PhD.
Annotation:Chemoprotective and photoprotective effect of the essential oil from lavender (Lavandula angustifolia), as well as the knowledge about mechanism of its action is not yet sufficiently described in literature. The project is focused on complex evaluation of antioxidant properties of the essential oil from lavender (LO) with specific interest on protective properties against UV radiation. UV radiation is considered to be the key risk factor in the etiology of skin cancer which incidence has increasing trend line worldwide. Chemo- and photoprotective properties effects of LO will be studied using in vitro models of healthy normal skin (human keratinocytes HaCaT, primary murine keratinocytes) and on melanoma cell line HMB-2. Using comprehensive approaches from biochemistry, biology, molecular biology and genetics will enable us to confirm possible protective effects of LO on normal and cancer skin cells, plus to help to understand the mechanism of action of LO.
Duration: 1.1.2016 - 31.12.2019

Experimentálna t - The application of combined therapy to suppress secondary damage after spinal cord trauma
Aplikácia kombinovanej terapie na potlačenie sekundárneho poškodenia miechy po traume
Program: APVV
Project leader: RNDr. Lukáčová Nadežda DrSc.
Annotation:Despite progress made in the understanding of the pathogenesis of traumatic spinal cord injury in humans, and in improvements of its early diagnostics, we still do not have effective treatment. Mechanisms of secondary injury, as a consequence of primary injury, represent extensive windows for therapeutic manipulations by appropriate exogenous and endogenous interventions. We intend to promote axon regeneration and functional recovery after SCI by blocking the signaling pathways for axonal growth inhibitors in combination with therapeutic effect of the biodegradable material, gradually releasing neurotrophic factors. Because the growth of axons into a spinal cord lesion can be disorganized, we suppose, that long term application of weak electrical field (ES) over injurz site can support their arrangement in linear alignment present in the intact spinal cord. In addition, our objective is to guide the axonal alignment, by AAV9 - GDNF vector, applied subpialy in the vicinity of traumatic lesion. We suppose, that the use of adeno-associated viral (AAV) vector allow long-term and stable transgene expression of GDNF and in combination with ES can be promising intervention for neurogenesis and remyelination, and functional recovery.
Duration: 1.7.2016 - 30.6.2020

The safety of use of analogs of the endocrine disruptor Bisphenol A: evaluation of effects on in vitro models of ovarian intrafollicular processes and and ovarian cancer cell lines
Bezpečnosť používania analógov endokrinného disruptoru Bisfenolu A: hodnotenie účinkov v in vitro modeloch ovariálnych intrafolikulárnych procesov a ovariálnych nádorových líniách
Program: VEGA
Project leader: Mgr. Bujňáková Mlynarčíková Alžbeta PhD.
Duration: 1.1.2018 - 31.12.2020

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

Biomarkers for assessment of individual radiosensitivity in breast cancer therapy
Biomarkery individuálnej citlivosti k žiareniu v terapii pacientok s nádorom prsnika
Program: VEGA
Project leader: RNDr. Marková Eva CSc.
Annotation:Developing validated biomarkers for radiosensitivity has been recently identified as a critical research gap in successful treatment of breast cancer and avoiding side effects of radiation. Based on our previous results we hypothesize that combined in vitro and in vivo estimation of radiation response may cover many processes involved in side effects such as DNA damage and repair, cell death, phagocytosis, hematopoiesis, and repopulation. We will collect blood samples from patients treated for breast carcinoma before, during, and after radiotherapy. Radiation response will be analyzed in vitro and in vivo in relevant blood cell subpopulations responsible for cell repopulation and phagocytosis of apoptotic cells. Biomarkers for DNA repair foci and apoptosis will be studied. The side effects and clinical data will be correlated with biomarkers of radiation response. Biomarkers, which will correlate with side effects, will be suggested for integrated tool in assessment of individual radiosensitivity.
Duration: 1.1.2017 - 31.12.2020

Detailed characterization and further improvement of system for induction of synchronous meiosis at optimal temperature
Bližšia charakterizácia a vylepšenie systému indukcie synchrónnej meiózy pri optimálnej teplote
Program: VEGA
Project leader: RNDr. Kretová Miroslava PhD.
Annotation:The central aspect of sexual reproduction is the generation of haploid gametes from diploid cells in a process called meiosis. Although we understand certain aspects of regulation of meiotic cell division, we are far from a thorough understanding of it. Here, we plan to make a further improvements of newly developed system of pat1-as-induced synchronous meiosis at optimal temperature, with emphasis on increasing the sensitivity and specificity of inhibition of Pat1-as protein kinase by ATP analogs. Additionally, we will study and characterize in more details the molecular mechanisms driving pat1-as-induced meiosis, which are responsible for correction of most of the aberrant events observed in pat1-114-induced meiosis. Developed system of synchronous meiosis at optimal temperature will open the gate to a deeper and more reliable biochemical dissection of mechanisms regulating the processes of meiotic chromosome segregation.
Duration: 1.1.2016 - 31.12.2019

Cellular and molecular traits of human metastasis-initiating cells at different stages of metastasis development.
Bunkové a molekulárne vlastnosti ľudských buniek iniciujúcich rast metastáz v rôznom štádiu metastatického procesu.
Program: VEGA
Project leader: Ing. Poturnajová Martina PhD.
Annotation:Metastatic dissemination is a critical step in malignant progression and major factor contributing to cancer mortality. Colonizing cancer cells must develop resistance to host-tissue defences to survive and retain tumor-initiating capacity, giving rise to overt metastasis. Such metastasis- initiating cells (MetIC) have to infiltrate distant tissue, survive as disseminated seeds, adapt to supporting new niches and initiate tumor. We will use metastatic human colorectal cancer HT-29/EGFP/FUR in comparison to HT-29/EGFP cells and aggressive melanoma human cell line EGFP-A375/Rel3, prepared in our lab. On established metastatic model in vivo we would like to establish tumor cell lines containing MetIC in the different stages of metastases development. Subsequently, we would like to examine the properties of cancer cell population enriched for MetIC by functional and expression analysis and find out if targeting of the selected tumorigenic population by RNA interference can inhibit tumor growth.
Duration: 1.1.2017 - 31.12.2020

MITOGEN - Whole exome sequencing in patients with primary mitochondriopathies
Celoexómové sekvenovanie u pacientov s podozrením na primárne mitochondriopatie
Program: VEGA
Project leader: RNDr. Gašperíková Daniela DrSc.
Annotation:Primary mitochondriopahies form a clinically and genetically heterogeneous group of inherited disorders that arise as a result of a defect in mitochondrial energetic metabolism. After the main causes of mitochondrial function impairment having been excluded, further diagnostics keeps being routinely inaccessible. Aim of this project is to identify new and rare genetic causes of mitochondriopathies using next-generation sequencing methods. Families, where routine diagnostics failed to identify genetic cause of disease, will be selected from already established DNA bank as well as from ongoing clinical recruitment. In these families, whole mtDNA and/or whole exome will be sequenced. The causality of candidate variants identified by bioinformatic analysis will be evaluated by co-segregation in the family and by functional analysis, if possible. The project will bring new theoretical knowledge about etiopathogenesis of primary mitochondrial disorders that is directly applicable in clinical practice.
Duration: 1.1.2017 - 31.12.2020

Whole exome sequencing in multiplex families with hereditary hearing loss in Slovakia: identification of novel gene variants
Celoexómové sekvenovanie v multiplexných rodinách s hereditránou poruchou sluchu na Slovensku: identifikácia nových génových variantov
Program: VEGA
Project leader: RNDr. Gašperíková Daniela DrSc.
Duration: 1.1.2016 - 31.12.2019

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. Hunáková Ľuba CSc.
Duration: 1.1.2018 - 31.12.2021

Diastolic function of the ryanodine receptor and generation of arrhythmogenic calcium waves
Diastolická funkcia ryanodínového receptora a tvorba arytmogénnych vápnikových vĺn
Program: VEGA
Project leader: RNDr. Zahradníková, ml. Alexandra PhD.
Annotation:In some acquired and genetic arrhythmias, anomalies in calcium release occur during the diastole, which may result in formation of calcium waves that initiate cardiac arrhythmias. Proper diastolic function of the system of calcium homeostasis involves regulation of diastolic calcium release by ryanodine receptors. Anomalous calcium release from the viewpoint of calcium wave formation is not sufficiently understood. We will concentrate on determination of the relationships between localization of dyads as the sites of calcium release and formation of calcium waves, and on their development during maturation and physiological hypertrophy of myocytes. The outcome of the project will be a better understanding of the factors governing calcium homeostasis in cardiac myocytes and their impairment leading to calcium waves.
Project web page:http://confolab.sav.sk/ovsb/projekty/aktivne-projekty/vega-2-0143-17/
Duration: 1.1.2017 - 31.12.2019

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 - 31.12.2021

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

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

Characterization of effects of neonatal exposure to nanoparticles in selected brain structures and reproductiveorgans in adult and infantile female rats
Charakteristika účinkov neonatálneho podania nanočastíc vo vybraných oblastiach mozgu a reprodukčných orgánoch u infantilných a dospelých samíc potkana
Program: VEGA
Project leader: Mgr. Scsuková Soňa CSc.
Annotation:The development of nanomaterials (NMs)/nanoparticles (NPs) for biomedical and commercial applications is undergoing a dramatic expansion. As the range of NP types and applications increases, their potential toxicities and properties must be understood. Evaluation of potential adverse effects of NPs and mechanism of their action on neuroendocrine, reproductive or immune systems is required. The present project will be focused on characterization of effects of neonatal exposure to selected NPs (PEG-b-PLA, TiO2) on expression of genes/proteins specific for reproductive neuroendocrine system (hypothalamus, pituitary, specific brain areas) and reproductive organs (uterus, ovary) in adult and infantile female rats. Selected markers of inflammation will be examined in brain and reproductive tissues. The observation of selected endpoints on tissue, cell, protein and gene levels will allow to record some changes/disturbances and provide new knowledge to guide safe and sustainable development of new NMs/NPs.
Duration: 1.1.2017 - 31.12.2019

CTC - 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: APVV
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

IBANTOXCGNT - Identification of biomarkers associated with late toxicity of chemotherapy in testicular germ cell tumors.
Identifikácia biomarkerov asociovaných s neskorou toxicitou chemoterapie u germinatívnych nádorov testes
Program: APVV
Project leader: RNDr. Gronesová Paulína PhD.
Annotation:Testicular germ-cell tumor (TGCTs) survivors are men cured from TGCTs with multimodality treatment including cisplatin based chemotherapy. Extraordinary survival with duration for several decades is often stigmatised by morbidity associated with late toxicity of chemotherapy. Number of studies report secondary malignancies, cardiovascular disease, neurotoxicity, nephrotoxicity, pulmonary toxicity, hypogonadism, infertility, psychological, behavioral and cognitive disorders. These late toxicities negatively influence quality of survivors lives and may be contributing factor on increasing mortality in this population. The data suggest that further research in this area is needed and associations with clinical, biochemical and genetic biomarkers need to be identified. Systematic physical activity is shown to have positive effects on cardiopulmonary and muscle function in general population but effects in TGCT survivors remain to be explored. This is first translational study with excersise-intervention program conducted in TGCT survivorship research and strongly benefical clinical outcome is expected.
Duration: 1.7.2016 - 30.6.2020

IBANTOXCGNT - Identification of biomarkers associated with late toxicity of chemotherapy in testicular germ cell tumors
Identifikácia biomarkerov asociovaných s neskorou toxicitou chemoterapie u germinatívnych nádorov testis
Program: APVV
Project leader: Mgr. Ukropec Jozef DrSc.
Duration: 1.7.2016 - 30.6.2020

APOCRIGEN - Identification of molecular-genetic determinants of apocrine secretion
Identifikácia molekulárno-genetických determinantov apokrinnej sekrécie
Program: APVV
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

DEAFGEN - Identification of novel gene variants of hereditary hearing loss based on nationwide screening
Identifikácia nových génových variantov dedičných porúch sluchu na báze celonárodného skríningu
Program: APVV
Project leader: RNDr. Gašperíková Daniela DrSc.
Duration: 1.7.2016 - 30.6.2020

PSYSOMSTRESS - 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: APVV
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

IPABH - The identification of EBHS virus and selected pathogens as possible cause of the European brown hare (Lepus europaeus) population decline in Slovakia
Identifikácia vírusu EBHS a vybraných patogénov ako možnej príčiny poklesu početnosti zajaca poľného (Lepus europaeus) na Slovensku
Program: APVV
Project leader: RNDr. Kúdelová Marcela DrSc.
Annotation:European brown hare is one of our most traditional game animals. Since 1975, rapid decline of hare population in Slovakia is registered. It is known that hares suffer from several diseases as tularaemia, leptospirosis, Q-fever, brucellosis, toxoplasmosis, chlamydiosis and others, including coccidiosis and helminthoses as well as European brown hare syndrome (caused by viral infection with EBHSV) which might be the reasons of hare population decline. Slovakia exports hares into some European countries and it is necessary to avoid undesirable transmission of pathogens. The main aim of project is the identification of epidemiologic status of EBHSV and other diseases of brown hares mentioned in Slovakia with emphasis on correlation between health status and population dynamics. Further aims are phylogenetic analysis of Slovakian EBHSV isolates and introducing of methodologies allowing determination of antibodies against pathogens useable for monitoring of epidemiologic situation within free-living hare´s population in Slovakia. The implementation of the project gives the possibility of applying the most recent modern biotechnologies developed by basic research in solving recent tasks of applied research.
Duration: 1.7.2016 - 30.6.2020

ImmunoGEN - Implementation of modern genomic analyzes to improve clinical diagnostic and therapeutic procedures of Immune Disorders
Implementácia moderných genomických analýz na zlepšenie klinických diagnostických a terapeutických postupov imunitných porúch
Program: Iné projekty
Project leader: prof. RNDr. Kádaši Ľudevít DrSc.
Duration: 1.12.2018 - 31.12.2020

Imunomodulatory properties of the murine herpesvirus M3 protein and the role of ticks in herpesvirus circulation in nature
Imunomodulačné vlastnosti M3 proteínu Myšieho herpetického vírusu a úloha kliešťov v cirkulácii herpesvírusu v prírode
Program: VEGA
Project leader: RNDr. Kúdelová Marcela DrSc.
Annotation:Murine herpesvirus 68, firstly discovered in murid rodents in Slovakia codes for unique M3 protein with great potency to modulate host immune response, thus useful in therapy of imflamation and diseases related to dysregulation of chemokine network. The aim is to continue in study on domains critical for M3 protein functioning as viral receptor of chemokines laying stress on recombinat M3 proteins (prepared in insect and/or mammalian cells) modified to increase/block binding to chemokines. Attention will be payed to MCP-1 suggested as crucial in defense against herpesviral infection of CNS. Further aim is to affirm preliminary finding that blood-feeding arthropods spp. Dermacentor and Ixodes, the most common at territory in Slovakia, could be a vector transmitting MHV68 from infected to uninfected host. Required criteria for confirmation of MHV68 as a novel arbovirus, 2nd DNA arbovirus and 1st herpesviral to date, will be assessed to clarify the tick role in MHV68 circulation in nature.
Duration: 1.1.2017 - 31.12.2020

Induction of apoptosis by betulinic acid coupled to magnetite nanoparticles in human colorectal cell lines
Indukcia apoptózy kyselinou betulínovou naviazanou na magnetické nanočastice v ľudských nádorových bunkách hrubého čreva
Program: VEGA
Project leader: RNDr. Šramková Monika PhD.
Annotation:The incidence of colorectal cancer has still alarming trend worldwide with the frequent occurrence of resistance towards chemotherapy, especially in metastasis. Therefore, the development of drugs that can bypass the chemoresistance and/or augment the cytotoxicity of conventional chemotherapeutics can be the strategy. Betulinic acid (BA) is such a compound. Despite the number of studies describing the biological effect of BA, characterization of its coupling to magnetite nanoparticles (MNP-BA) used as nanovectors still remains to be addressed. Our project is aimed at a comprehensive assessment of properties of MNP-BA with specific regard to its cytotoxic, cytostatic and genotoxic effects in colorectal cell lines sensitive/resistant to chemotherapeutics. A complex approach from biochemistry, biology, and molecular biology will enable us to show whether MNP-BA is able to act as an anticancer drug by inducing the apoptosis in resistant cancer cells.
Duration: 1.1.2017 - 31.12.2020

Induction of antiviral immunity with recombinant influenza virus on mouse model.
Indukcia protivírusovej imunity rekombinantným vírusom chrípky na myšom modeli.
Program: VEGA
Project leader: RNDr. Kostolanský František CSc.
Annotation:The main goal of the submitted project is the examination of conserved antigens of influenza A virus as inductors of broadly cross-protective immune response against influenza infection. Two IAV proteins, M2e ectodomain and HA2 gp, the light chain of hemagglutinin, will be used as immunogens. These proteins will be applied to mice in the form of cloned multifunctional expressed vector pTriEx-4 comprising these viral antigens M2e resp. HA2 to achieve their optimal presentation. Second way of immunization will utilize the live attenuated influenza A virus as a vector presenting M2e protein and HA2 gp. The increased (enhanced) presentation will be ensured by the insertion of encoding sequences into the NS1 gene and by multiplication of viral vector in immunized animal. The efficacy of immunization protocols will be evaluated by monitoring the antigen-specific antibody and T-cell immune response of immunized mice and ” in vivo” by monitoring the protection of immunized mice from the lethal influenza A infection.
Duration: 1.1.2017 - 31.12.2020

Interaction of hypoxia with the signaling pathways implicated in differentiation, tumor progression and metastasis.
Interakcia medzi hypoxiou a signálnymi dráhami zapojenými v diferenciácii, nádorovej progresii a metastázovaní.
Program: VEGA
Project leader: RNDr. Takáčová Martina PhD.
Annotation:Hypoxia is an important aspect of the tumor microenvironment, which along with other components (stromal cells, extracellular matrix proteins, growth factors, etc.) plays a crucial role in influencing tumor and stem cell behavior. Through the interaction with autocrine/paracrine oncogenic signaling pathways, such as Wnt, Notch, TGFb, and receptor tyrosine kinases (c-Met, EGF, PDGF), hypoxia has the potential to inhibit tumor cell differentiation and to maintain tumor cells in an undifferentiated stem cell-like state. This project will focus on the interaction between hypoxia and previously mentioned signaling pathways in the control of carbonic anhydrase IX expression and function (both in pH regulation and migration). Understanding of this interplay is critical for rational application of CA IX as diagnostic and therapeutic target. Therefore, we will use both cell cultures and tissue samples from different carcinomas to elucidate the role of CA IX as indicator of differentiation, progression and metastasis.
Duration: 1.1.2016 - 31.12.2019

Is DNA repair beyond good curability in testicular germ cell tumours?
Je oprava DNA zodpovedná za dobrú liečiteľnosť testikulárnych nádorov zo zárodočných buniek?
Program: VEGA
Project leader: RNDr. Jurkovičová Dana PhD.
Annotation:Testicular germ cell tumours (TGCT) represent the main type of malignity in young men. It is believed that disease relapse can be associated with DNA repair. We hypothesize that refractory TGCT patients display changed levels of DNA repair proteins compared to cured patients. Therefore, we intend to compare expression of the selected DNA repair proteins in both groups of patients. We expect that an increased level of these proteins is responsible for higher extent of DNA damage that we have preliminary observed in refractory patients. We plan to follow DNA strand breakage before and after receiving chemotherapy in refractory patients, as well as patients with durable complete remission. In addition, we possess TGCT primocultures established in our laboratory, a few commercially available TGCT cell lines, and cell lines established using xenographs, which will be used to monitor repair of cisplatin (CDDP)-induced DNA damage to verify our hypothesis on association between DNA repair and refractoriness in TGCT.
Duration: 1.1.2017 - 31.12.2020

Discovery of clinically relevant proteins and their application in more reliable diagnostics of Q fever
Klinicky relevantné proteíny a ich aplikácia v spoľahlivejšej diagnostike Q-horúčky.
Program: VEGA
Project leader: Mgr. Flores-Ramírez Gabriela PhD.
Annotation:Coxiella burnetii (C. burnetii) is the etiological agent of Q fever. These intracellular bacteria can provoke zoonosis from farm animals. During the last decade, several outbreaks in Europe (Hungary, Germany, France, Slovakia & Netherlands) of the illness occurred causing both, economical losses in the livestock industry and the spread of the infection in humans. Due to many similar symptoms with commonly occurring infections, its clinical diagnosis is very challenging. Thus, a strong effort should be taken to raise the awareness of public and develop a reliable strategy for an accurate diagnosis.The main goal of this project proposal is to discover clinically relevant proteins for development of a reliable Q fever diagnostic kit using immunoproteomics.
Duration: 1.1.2018 - 31.12.2020

Localization and role of endothelial nitric oxide synthase in the neurogenic region of the rat during postnatal period
Lokalizácia a úloha endotelovej syntetázy oxidu dusnatého v neurogénnej oblasti potkana v postnatálnom období
Program: VEGA
Project leader: RNDr. Martončíková Marcela PhD.
Duration: 1.1.2017 - 31.12.2019

Mechanism of anti-tumor activity of realgar nanoparticles and its synergism with anti-myeloma agents
Mechanizmus protinádorového účinku nanočastíc realgaru a synergia s anti-myelómovými liečivami
Program: VEGA
Project leader: RNDr. Jakubíková Jana PhD.
Duration: 1.1.2017 - 31.12.2019

Tolerance - 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: APVV
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 - 31.12.2021

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

METVIDIS - 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: APVV
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

TANDEM - 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: APVV
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

MIR-ENDOM - Micro-RNA expression profiles for discrimination of endometrioid and serous types of endometrial cancer
MikroRNA expresné profily na diskrimináciu endometrioidného a serózneho typu karcinómu endometria
Program: Iné projekty
Project leader: RNDr. Fridrichová Ivana CSc.
Annotation:Endometrial carcinoma (EC) belongs to the most common gynaecological malignancies with increasing incidence and mortality. However, regarding to early diagnosis the patients with endometrioid type of tumour enjoy the beneficial prognosis with 75% survival. The classification of EC is based on cytomorphological criteria; however, the actual trend in personalized therapy requests the identification of new molecular markers and taxonomy involving the genetic and epigenetic alterations. Genomic analyses defined the different mutation profiles in histological subtypes and molecular subgroups, but criteria for more exact classification were not fulfilled. The appropriate solution could bring the study of epigenetic alterations,namely the cancer specific expression profiles of microRNAs. In present project, we will select the specific microRNA expression profiles for discrimination of morphologically defined endometrioid and serous EC and also in endometrioid type between the stages of differentiation. Consequently, selected microRNA expression profiles will be used for characterization of rare EC types. Based on the correlation of laboratory results with clinical and histopathological data we will evaluate the clinical utility of selected microRNA expression profiles for more detail molecular classification of EC.
Duration: 1.12.2018 - 31.12.2020

IMMUNOMOD - Immune modulation by cytomegalovirus and its immunotherapeutic potential.
Modulácia imunitnej odpovede cytomegalovírusom a jej imunoterapeutický potenciál.
Program: APVV
Project leader: Mgr. Nemčovičová Ivana PhD.
Annotation:Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that persistently infects the majority of the world’s population (more than 80% infected of Slovak adult population). HCMV is a paradigm for viral immune evasion that maintains a number of immunomodulatory genes that act to suppress Natural Killer (NK) as well as T cell functions. Characterizing the structural and molecular basis of the host-virus protein interactions is critical to further our understanding of the immune equilibrium that is established during viral infection, and why disease can occur if this balance is disrupted. The ligands and receptors of Immunoglobulin (Ig) or Tumour Necrosis Factor (TNF) families are critical for host defence; therefore we have an interest in delineating evasion strategies used by virus to modulate immune recognition. In this regard, we are planning a preparation and molecular characterization of selected set of recombinant viral and human genes that are associated with cytotoxicity and viroprotectivity processes in the cell while these events will also be monitored. We expect by using this cross-disciplinary approach we will able to design and characterize suitable candidates with high immunomodulatory activity. In summary, project aims to examine the targets and mechanisms by which HCMV immunomodulation is achieved, and therefore discuss the development of immunomodulatory biologics for the treatment of HCMV infection. In addition, the understanding of mechanism by which HCMV modulates immune effector pathways highlights its possibility being used as a vaccine vector for the treatment of cancer or other autoimmune diseases.
Duration: 1.7.2015 - 30.6.2109

Molecular epidemiology of viruses of fruit trees and grapevines across the agroecological interface
Molekulárna epidemiológia vírusov ovocných drevín a viniča hroznorodého naprieč agroekologickým rozhraním
Program: VEGA
Project leader: Ing. Glasa Miroslav DrSc.
Annotation:The project focused on identification and characterisation of the diversity and distribution of viruses of fruit trees and grapevine in its entirety across agroecological interface, which represents a dynamic border between wild and agricultural communities, at the same time a potential reservoir of new and emerging viral pathogens and an outbreak spot of fast epidemics. Besides the standard methods, the nonspecific next generation sequence (NGS) tools will be used for the molecular characterisation of pathogens, with a possibility to detect new viruses or their highly divergent forms. Molecular variability will be assessed in relation to the virus pathogenicity and etiology. In case of the identification of new or up to now undetected viruses, the obtained sequence data will be used for development of detection methods applicable in a routine diagnostic. The results acquired will provide the original data for establishment or optimisation of phytosanitary and control measures.
Duration: 1.1.2016 - 31.12.2019

UL144 - 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

Molecular mediators of physical exercise and carnosine induced effects in patients with preclinical and early stage neurodegenerative disease
Molekulárne mediátory účinkov fyzickej aktivity a karnozínu u pacientov s preklinickými a včasnými štádiami neurodegeneratívnych ochorení
Program: APVV
Project leader: doc. MUDr. Ukropcová Barbara PhD.
Duration: 1.7.2016 - 30.6.2020

Molecular mechanisms of thermogenesis in brown fat in humans in relationship to obesity, physical activity and hardening
Molekulárne mechanizmy termogenézy v hnedom tuku u človeka vo vzťahu k obezite, pohybovej aktivite a otužovaniu
Program: VEGA
Project leader: Mgr. Ukropec Jozef DrSc.
Duration: 1.1.2017 - 31.12.2019

MOFAREX - Experimental approaches in vitro and in vivo to inovative therapy of rheumatoid arthritis based on molecular-pharmacological principles
Molekulárno-farmakologické prístupy k inovatívnej terapii reumatoidnej artritídy hodnotenej v experimentálnych podmienkach in vivo a in vitro
Program: APVV
Project leader: Ing. Zorad Štefan CSc.
Annotation:The project is based on the study of the therapeutic potential of selected compounds for the therapy of rheumatoid arthritis (RA), and especially, for the combined therapy with methotrexate. The substances studied will be natural and synthetic low molecular weight compounds and their derivatives (glutathione, meso-2,3- dimercaptosuccinic acid, N-butyldeoxynojirimycin); immunomodulators of bacterial origin (different probiotic strains of Lactobacillus); the substances of plant origin isolated from plants, their derivatives and complexes (astaxanthin, complex quercetin- phosphatidylcholine (phytosome), carnosic acid, carnosol, sulphoraphane, diplacone, glabridin, ginkolides, bilobalide, feruloyl aldehyde and mono- and digalactosyldiacyl glycerol, epigallocatechin gallate, gallic acid, quinic acid, ellagic acid, fatsiflogin and robinin) and their corresponding standardized extracts; polysaccharides with different molecular weight and their derivatives (chitosan-glucan and chitosan isolated from the mycelium of Schizophyllum commune and their derivatives, sodium salt of hyaluronan of bacterial origin). The adjuvant arthritis model (AA) induced in Lewis rats will be used. We will characterize the development of AA and its pharmacological influence by parameters describing immunological, oxidative and inflammatory processes. The compounds evaluated will be applied in a preventive-therapeutic and therapeutic design. Subchronic AA will be completed also by the acute carrageenan-induced inflammation model. The therapeutic value of selected substances will be verified in collagen model of arthritis at the end of the project. With the aim to analyze their molecular mechanism of action, along with in vivo evaluation of the compounds studied, experiments on chemical systems and cell cultures will be performed. Pharmacological modulation of the cardiovascular complications in arthritis will be also analyzed using functional parameters of isolated hearts in ischemia-reperfusion.
Duration: 1.7.2016 - 30.6.2020

Molecular-mechanistic aspects of functioning of the developmentally-linked malate dehydrogenases complex in Drosophila melanogaster.
Molekulárno-mechanistické aspekty fungovania komplexu vývinovo-spriahnutých malát dehydrogenáz u Drosophila melanogaster.
Program: VEGA
Project leader: RNDr. Farkaš Robert CSc.
Annotation:Significantly less attention was devoted to the regulation of expression of the genes encoding proteins involved in basal metabolism than those playing crucial role in development. An exception are proteins (enzymes) that are useful diagnostic markers. In recent past we have shown that group of hormonally responsive malate dehydrogenases (MDHs) of Drosophila characterized at molecular level in our laboratory and found to play an important role in the control of development, incl. the program determining number and length of larval instars. Since this is the first finding of this type, we plan to use excellent genetic model of Drosophila to dissect signaling pathway(s) controlling transduction of malate-pyruvate shuttle that via MDHs interactions appear to regulate allometric growth and morphogenesis. The aim is to identify such interactions followed by their molecular characterization since they may bear features of evolutionarily highly conserved principle in such divergent organisms as insects and mammals.
Duration: 1.1.2017 - 31.12.2020

DEPOXIN - Molecular bases of depressive disorders in children and adolescents, effect of omega-3 fatty acids and oxidative stress
Molekulové základy depresívnej poruchy u detí a adolescentov, vplyv omega-3 mastných kyselín a oxidačný stres
Program: APVV
Project leader: prof. PharmDr. Ježová Daniela DrSc.
Annotation:Mood disorders is a serious global problem of child psychiatry. Pathophysiology of depressive and anxiety disorders (DD) are not fully known. DD patients were found to have activated the inflammatory response through increased production of cytokines, a failure in the metabolism of serotonin (ratio tryptophan/kynurenine) and other neurotransmitters (release of pterins).In patients with DD reduced levels of omega-3 fatty acids (FA) were found, which can be involved in modulation of membrane fluidity and transmission of neurotransmitters. The consequence may be increased lipid peroxidation of FA, which can influence cell signaling, synthesis of eicosanoids, inflammation, shorten the length of telomeres, and oxidative stress. Our goal is to study the relationship between the level of unsaturated FA, depressive symptoms, selected biochemical parameters focused on lipid profile, subfractions of LDL and HDL lipoproteins, cholesterol in membranes, nonspecific inflammation and oxidative stress, to monitor the participation of neurohormonal regulation in pathophysiology of DD. To assess the influence of 3-month administration of omega-3 fatty acids - eicosapenthaenoic (EPA) and docosahexaenoic (DHA) acids - on the observed clinical and biochemical parameters in a placebo controlled study (60 patients, 6-18 yrs.) and from our results to deduce mutual interactions at the molecular level.
Duration: 1.7.2016 - 30.6.2020

MOR4CML - Multivalent morpholino-based antisense system for CML
Multivalentný morpholino-based antisense systém pre CML
Program: APVV
Project leader: RNDr. Gábelová Alena CSc.
Annotation:The proposed MOR4CML project is dedicated to an innovative, morpholino-based antisense concept for BCR-ABL silencing in patients with chronic myelogenous leukemia (CML). Due to its original design and mechanism of action, the suggested concept allows to significantly enhance both selectivity towards CML cells and sequence-mediated specificity towards BCR-ABL mRNA. It is expected that the presented interdisciplinary effort will overcome the main issues that have so far hindered introduction of BCR-ABL antisense-therapeutics into clinical practice. If successful, the proposed concept is also expected to provide a tremendous curative potential not only in CML but also in all diseases with known molecular basis, where a particular protein plays a causal role in disease pathophysiology.
Duration: 1.7.2016 - 30.6.2020

Tumor heterogeneity in multiple myeloma: evolution and clinical relevance
Nádorová heterogenita v mnohopočetnom myelóme: evolúcia a klinická významnosť
Program: APVV
Project leader: RNDr. Jakubíková Jana PhD.
Duration: 1.7.2017 - 30.6.2021

BIONANOGOLD - 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: APVV
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

NeurOnco - 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: APVV
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

Neuroprotection in the process of ischemic tolerance acquisition from the perspective of rat brain pathways monitoring (proteomic MALDI-TOF/TOF study)
Neuroprotekcia v procese získania ischemickej tolerancie z pohľadu sledovania reakčných dráh v mozgu potkana (proteomická MALDI-TOF/TOF štúdia)
Program: VEGA
Project leader: MVDr. Némethová Miroslava PhD.
Annotation:Project is devoted to the global brain ischemia study, mainly to processes and mechanisms involved in the pathophysiology of CNS ischemic injury. Targeted examining of neuroprotective mechanisms and finding possibilities of brain cells protection after ischemia are primary topics of the project. It is known that neurons have a natural ability to tolerate damage caused by ischemic episode. A conditioning or second stress seems to be starting condition of this process, if used prior to ischemia or during postischemic reperfusion interval within two days after ischemia. This procedure is able to prevent the occurrence of delayed neuronal death. Implementation of the objectives of the project will be based on proteomic analysis of ischemic and tolerant brain tissue by mass spectrometry. Identification of differentially expressed proteins along with their classification into metabolic and signaling pathways will allow us to monitor the mechanisms involved in the targeted protection and survival of neurons.
Duration: 1.1.2018 - 31.12.2020

Novel additive antitumour effects of nuclear retinoid X receptor (RXR) ligands of natural and synthetic character in human breast and renal carcinoma cells
Nové aditívne protinádorové účinky ligandov jadrových retioidných X receptorov (RXR) prírodného a syntetického charakteru v ľudských nádorových bunkách prsníka a obličky
Program: VEGA
Project leader: Mgr. Macejová Dana PhD.
Duration: 1.1.2017 - 31.12.2019

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

NO-NEW-REG - New regulatory effects of nitric oxide and their role in the development of essential hypertension
Nové regulačné účinky oxidu dusnatého a ich úloha v rozvoji esenciálnej hypertezie
Program: APVV
Project leader: Mgr. Mišák Anton PhD.
Annotation:High blood pressure is a main risk factor in sustained increased morbidity and mortality of humans suffering cardiovascular diseases. Understanding of causes leading to hypertension enable to reveal new preventive and therapeutic decisions. A new regulatory system involved in vessel tree regulation seems to be neuronal NO-synthase (nNOS) and its interactions with other regulatory systems. On the level of the kidney nNOS signal pathway interferes with renin-angiotensin system (RAS) and sulfide signalization (H2S), and the interactions among them are the unexplored area of regulatory mechanisms. nNOS in macula densa stimulate renin syntesis and via it influences RAS and sympathetic nerve system, on the other hand, H2S inhibits renin synthesis. Moreover, the regulatory pathways of nNOS and also endothelial eNOS could interact with endogenous NOS inhibitor, asymmetric dimetylarginine ADMA, on local as well as systemic level. The aim of the project is to study the effect of interactions of NO/nNOS/eNOS signalization with mentioned regulatory pathways (RAS, H2S, ADMA) on cardiovascular system and to find out their role in the specificity of nNOS and/or eNOS action in the conditions of essential hypertension. The availability of the results will be reached via using complex approach (functional, molecular, morphological). Moreover, on the level of acute experiments, we will confront selected biochemical markers of perivascular adipose tissue (plasma/serum) as well as vasoactive responses of arteries isolated from normotensive and hypertensive rats with biochemical markers and reactivity of vessels isolated after nephrectomy from normotensive patients and patients with essential hypertension.
Duration: 1.7.2016 - 30.6.2020

NO-NEW-REG - New regulatory effects of nitric oxide and their role in the development of essential hypertension
Nové regulačné účinky oxidu dusnatého a ich úloha v rozvoji esenciálnej hypertezie
Program: APVV
Project leader: Ing. Zorad Štefan CSc.
Annotation:High blood pressure is a main risk factor in sustained increased morbidity and mortality of humans suffering cardiovascular diseases. Understanding of causes leading to hypertension enable to reveal new preventive and therapeutic decisions. A new regulatory system involved in vessel tree regulation seems to be neuronal NO-synthase (nNOS) and its interactions with other regulatory systems. On the level of the kidney nNOS signal pathway interferes with renin-angiotensin system (RAS) and sulfide signalization (H2S), and the interactions among them are the unexplored area of regulatory mechanisms. nNOS in macula densa stimulate renin syntesis and via it influences RAS and sympathetic nerve system, on the other hand, H2S inhibits renin synthesis. Moreover, the regulatory pathways of nNOS and also endothelial eNOS could interact with endogenous NOS inhibitor, asymmetric dimetylarginine ADMA, on local as well as systemic level. The aim of the project is to study the effect of interactions of NO/nNOS/eNOS signalization with mentioned regulatory pathways (RAS, H2S, ADMA) on cardiovascular system and to find out their role in the specificity of nNOS and/or eNOS action in the conditions of essential hypertension. The availability of the results will be reached via using complex approach (functional, molecular, morphological). Moreover, on the level of acute experiments, we will confront selected biochemical markers of perivascular adipose tissue (plasma/serum) as well as vasoactive responses of arteries isolated from normotensive and hypertensive rats with biochemical markers and reactivity of vessels isolated after nephrectomy from normotensive patients and patients with essential hypertension.
Duration: 1.7.2016 - 30.6.2020

Novel synergistic antitumour properties ofnuclear retinoid X receptor (RXR) agonists as a consequence of the conditional RXR-RAR heterodimer formation in human breast cancer cells
Nové synergické protinádorové vlastnosti agonistov nukleárnych retinoidných X receptorov (RXR) ako následok vzniku "conditional" RXR-RAR heterodiméru v ľudských nádorových bunkách prsníka
Program: APVV
Project leader: Ing. Brtko Július DrSc.
Duration: 1.7.2016 - 30.6.2020

SGT - Of Sheep, Goats and Tick-borne Encephalitis virus
O ovciach, kozach a viruse kliestovej encefalitidy
Program: APVV
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

SPLICONC - 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: APVV
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

MICROBIOM - 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: APVV
Project leader: MUDr. Penesová Adela PhD.
Duration: 1.8.2018 - 30.6.2022

Pathogens and endosymbionts as components of the natural environment of the bloodsucking ectoparasites
Patogény a endosymbionty ako zložky prirodzeného prostredia krv cicajúcich ektoparazitov
Program: VEGA
Project leader: Mgr. Špitalská Eva PhD.
Duration: 1.1.2017 - 31.12.2020

Comparison of functional characteristics of adipose tissue-derived mesenchymal stromal cells isolated isolated from healthy donors and oncological patients
Porovnanie funkčných vlastností mezenchýmových stromálnych buniek izolovaných z tukového tkaniva prsníka od zdravých darcov a onkologických pacientok
Program: VEGA
Project leader: Mgr. Miklíková Svetlana PhD.
Annotation:Our study is focused on detection and characterisation of functional changes in mesenchymal stromal cells situated in tumor microenvironment, which could contribute to progression of benign disease to carcinoma. We suggest that better understanding of the specific features of tumor microenvironment could help to identify new prognostic markers for malignant disease and improve early detection and better prediction of disease progression.
Duration: 1.1.2017 - 31.12.2020

ENDONANOSAFE - Potential risk of metal and metal oxide nanoparticles used for biomedical applications: focus on reproductive and immune systems and brain
Potenciálne riziko nanočastíc kovov a oxidov kovov používaných v nanomedicíne: vplyv na reprodukčný a imunitný systém a mozog
Program: APVV
Project leader: Mgr. Scsuková Soňa CSc.
Annotation:The development of nanomaterials (NMs)/ nanoparticles (NPs) for biomedical applications, including medical imaging and drug delivery, is currently undergoing a dramatic expansion. The same properties that make the NMs beneficial for their applications may also affect their interactions with biological systems and have unintended consequences on human health. NMs in dependence on their physicochemical properties, composition, and functionalization are able to cross biological barriers and enter the central nervous system (CNS) and peripheral organs. Current data support the notion that different types of NPs are capable of altering the physiological activity of endocrine system. Moreover, it has been shown that NMs with potential use for diagnostic and therapeutic purposes might induce neurotoxic effects resulting in neurodegeneration in different CNS regions. Despite the studies carried out in recent years, current knowledge of underlying molecular mechanisms of NPs action on endocrine, especially reproductive system and CNS, and immune systems and oxidative status is still limited. In the present project, potential adverse effects of metal (gold, silver) and metal oxide (titanium and silicon dioxide) NPs on selected parameters of reproductive, neuroendocrine and immune system, and oxidative status will be assessed by series of in vitro and in vivo model systems. Natural plant substances with antioxidant and anti-inflammatory properties will be tested to overcome possible negative impact of NPs on the studied processes. Early identification of potential negative features of NMs using interdisciplinary research approaches (biological, toxicological, clinical, engineering) could minimize the risk of newly designed/developed NMs for biomedical applications.
Duration: 1.7.2016 - 30.6.2020

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

SMaRT - Therapeutic targeting of cancer stem cell markers circumventing cisplatin resistance in testicular germ cell tumors
Prekonanie rezistencie voči cisplatine u refraktérnych testikulárnych nádorov zo zárodočných buniek prostredníctvom terapie nasmerovanej voči markerom nádorových kmeňových buniek
Program: Iné projekty
Project leader: RNDr. Kozovská Zuzana PhD.
Annotation:The development of chemoresistance in testicular germ cell tumors (TGCT) represents a serious clinical problem associated with high morbidity and mortality in young men aged 20-40. Chemoresistance to cisplatin used in the first line TGCT treatment, is often associated with a subpopulation of cancer stem cells (CSC) in many types of tumors. In the project, we will focus on the intervention directed against the CSC markers in the refractory TGCT and its effect on resistance. We will introduce suitable experimental models: a) novel chemoresistant variants of the TGCT cell lines; and b) an experimental in vivo TGCTs model in the form of patient-derived xenografts. We will verify, whether cisplatin resistance can be circumvented in the refractory TGCTs using specific inhibitors, the CRISPR/Cas genome editing and the expression silencing using small interfering RNAs (siRNAs). The project will help to identify new therapeutic combinations that can be further tested in vivo on experimental animal models and in Phase II clinical trials.
Duration: 1.12.2018 - 31.12.2020

HippoOR - Prenatal and postnatal effects of delta and mu opioid receptor ligands on the hippocampal development and function.
Prenatálne a postnatálne účinky ligandov delta a mí opioidných receptorov na vývoj a funkciu hipokampu.
Program: APVV
Project leader: RNDr. Hlaváčová Nataša PhD.
Annotation:Ligands of opioid receptors δ (DOR) and μ opioid receptors (MOR) are commonly used in treatment of severe acute and chronic pain. DORs are involved also in mood disorders like depression and anxiety, which are related to the hippocampal function. Treatment with DOR ligands does not result in adverse effects including addiction, which are common with MOR ligands. However, much less is known about DOR – activated signaling pathways than about MOR – activated pathways. We will analyze the effect of acute (seconds to minutes) and chronic (hours to days) in in vitro and in vivo (prenatal and postnatal) administration of DOR ligands on the morphological and electrophysiological properties of rat hippocampal neurons and compare them with effects of MOR ligands and with effects of ligands specific for MOR-DOR heteromers. Further, involvement of calcium transporting proteins in signal transduction pathways activated by DORs and MORs ligands will be addressed by molecular biology methods. Possible remodeling of the dendritic spines will be investigated using transmission electron microscopy. Effect of DOR ligands on hippocampal plasticity in control and stressed rats will beexamined using behavioral tests and molecular neuroscience techniques. Excitability will be investigated in primary culture of hippocampal neurons by patch clamp and in situ by in vivo electrophysiology. Both models enable to follow effects of acute and chronic drug application as well as possible receptor desensitization and offer complementary advantages. Primary neuronal culture is the possibility to visually identify neurons, characterize in details both action potentials and underlying ionic currents and to correlate electrophysiology and molecular biology on the same batch of neurons. In vivo electrophysiology offers the possibility to measure neuronal activity within its normal environment including all interactions with other brain parts.
Duration: 1.7.2016 - 30.6.2020

Drug repurposing as a novel approach to therapy of colorectal carcinoma: molecular mechanisms and potential applications
Presmerovanie liekov na protinádorovú liečbu ako nový prístup k terapii kolorektálnych karcinómov: molekulárne mechanizmy a potenciálne aplikácie.
Program: VEGA
Project leader: RNDr. Baráthová Monika PhD.
Annotation:Drug repurposing is the identification of new therapeutic applications for drugs that have received approval for another purpose. B-blockers have the potential to be repurposed in therapy of colorectal cancers (CRC), which are the third most frequent cancer in men and the second most frequent cancer in women in the world. Many studies have supported the observation that ß-blockers produced an anticancer effect and improved survival of cancer patients. The main project objective is to elucidate effect of ß-blockers on hypoxia-regulated pathways in the process of tumor progression, to identify molecular pathways of interplay between stress hormones,ß-blockers and CAIX. Resistance to therapy of CRC occurs in most cases and allows cancer progression. This project can help to understand correlation between ß-blockers, drugs used in the chemotherapy of CRC, to elucidate interactions between comorbidities treatment and effectiveness of anticancer therapy and to reveal possible chemopreventive effect of ß-blockers.
Duration: 1.1.2016 - 31.12.2019

FLUBAC SYNERGY - Prevention and mechanism of synergy of influenza and bacterial coinfection
Prevencia a mechanizmus synergie chrípkovej a bakteriálnej koinfekcie s ťažkým priebehom ochorenia.
Program: APVV
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

Dbl2 - 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: APVV
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

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

SWIREG - Regulation of the Swi5-Sfr1 complex by protein phosphorylation
Regulácia komplexu Swi5-Sfr1 pomocou fosforylácie
Program: APVV
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 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: APVV
Project leader: RNDr. Zahradníková, ml. Alexandra PhD.
Duration: 1.7.2017 - 30.6.2021

rickcoxdiag - Rickettsiae and Coxiella burnetii, bacterial triggers of the "mysterious" diseases.
Rickettsiae a Coxiella burnetii, bakteriálne spúšťače "záhadných" ochorení.
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

MS-MIDY - Multiple sclerosis - The role of mitochondrial dysfunction in insulin resistance.
Sclerosis multiplex - Úloha mitochondriálnej dysfunkcie v inzulinovej rezistencii
Program: APVV
Project leader: doc. MUDr. Imrich Richard DrSc.
Annotation:Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) and is one of the most common neurological diseases, often leading to disability of the patients. The MS pathogenesis includes vascular and inflammatory components, however recently also the role of mitochondrial dysfunction being a hot topic in neurodegeneration. Current project is based on our previous project results, where we found signs of insulin resistance (IR) with hyperinsulinemia in patients with MS, which seems not to be related to chronic inflammation or low physical activity. Therefore aim of present project is to elucidate impact of mitochondrial dysfunction in the pathogenesis of impaired insulin action and its role in the neurodegenerative process. To test our hypothesis we will assess mitochondrial function, endothelial function, changes in membrane proteins and function of autonomic nervous system. Those parameters will be measured non-invasively and in samples of blood, cerebrospinal fluid and skeletal muscle. MS patients will be examined at the time of diagnosis and after 12 months of treatment, healthy subjects will be used as controls. We expect elucidation of insulin resistance cause and the role of mitochondrial dysfunction in pathogenesis of thedisease.
Duration: 1.7.2016 - 30.6.2020

Signaling pathways of morphological changes in neuronal cells
Signálne dráhy morfologických zmien u neuronálnych buniek
Program: VEGA
Project leader: Mgr. Bačová Zuzana PhD.
Annotation:Morphological changes of the neuronal cells are closely linked to changes in their function. The shape of nerve cells, neurite outgrowth and navigation are important not only in the development and in the formation of new synaptic connections, but various changes in the properties of neurons accompany diseases such as epilepsy, schizophrenia, autism and Alzheimer's disease. Processes leading to prolongation or retraction of neuronal cells projections are regulated by a number of modulators, which include neuropeptides. The aim of the present project is to investigate signaling pathways of selected neuropeptides, which can lead to the changes in the expression and phosphorylation of small GTPases (eg. RhoB, Cdc42, NWASP) involved in the process of extension in primary neurons and glia, or cell lines in vitro. We will focus on the mechanisms that lead to remodeling of the cytoskeleton and the role of calcium as a second messenger native from intracellular sources or its passage across the plasma membrane.
Duration: 1.1.2018 - 31.12.2020

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

Soluble and/or exosome-associated Carbonic anhydrase IX as a biologically active molecule.
Solubilná a/alebo exozómovo-viazaná karbonická anhydráza IX ako biologicky aktívna molekula.
Program: VEGA
Project leader: RNDr. Zaťovičová Miriam CSc.
Annotation:Many transmembrane proteins involved in signal transduction or other regulatory processes exist also in soluble single-molecule form and/or as extracellularly released complex structures called exosomes. Extracellular forms regulate the fate and physical location of membrane anchored proteins and have a significant impact on their biological functions. The proposed project is aimed at understanding the mechanisms of release of soluble and exosomal forms of the tumor associated protein carbonic anhydrase IX (CA IX) and their implications in cellular processes such as tumor cell adhesion, migration, and metastasis. In the project we will use not only latest in vitro methods of cell biology including measurements of cell parameters in real time but also in vivo experiments. Results of this project are expected to extend our knowledge on function of soluble CA IX ectodomain and exosomal CA IX as important intercellular messengers as well as potential non-invasive clinical biomarkers.
Duration: 1.1.2016 - 31.12.2019

IMUTRAFAK - Activity Assay of Transfer Factor, Immunostimulatory Drug from Leukocytes Extract And Its Preparation Standardization
Stanovenie aktivity transfer faktora, imunostimulačného preparátu z extraktu leukocytov a štandardizácia jeho prípravy
Program: APVV
Project leader: MVDr. Kopáček Juraj DrSc.
Annotation:Transfer factor (TF) is dialyzable leukocyte extract from peripheral blood of healthy donors that clearly demonstrates immunostimulatory effect in treatment of infectious diseases, allergies, some oncogenic disorders and immunodeficiencies. TF represent mixture of low molecular weight molecules (up to 10 KDa) predominantly of peptide origin that affect cell mediated immune response. Currently we are lacking information on molecular nature and composition of TF that hampered standardization of TF preparation, determination of its composition and efficacy and, consequently, its acceptance by drug control authorities. The main objectives of the project are analysis of TF treatment impact and characterization of its main components at molecular level; development and standardization of innovative methods of TF preparation and determination of its activity in vitro. For analytical separation of TF active components there will be used methods of HPLC and after demonstration of their biological activity they will be further characterized by proteomics methods. Concurrently there will be innovated methods for TF biological activity assays with focus of TF ability to modulate signal pathways of immune response in cells that will be studied by protein- and micro-array methods. The main goal of these studies will be development of simple quantitative method(s) for determination of TF biological activity. On basis of gained knowledge of main TF active components and innovative methods of their activity assay it will be possible to progress to TF preparation optimization with intention to improve therapeutic properties of current TF formulations. Data that will be obtained during the project will contribute to knowledge of TF biological effect; will open opportunities for its better, acceptable characterization and efficacy determination. The results could be transferred to TF production innovation for therapeutic purposes.
Duration: 1.7.2016 - 30.6.2020

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

ARIQUET - Investigation of anatomical-functional differences between the effects of aripiprazole and quetiapine, atypical antipsychotics with simiral terapeutic indications, but different impact on brain dopaminergic receptors, in experimental animals
Štúdium anatomicko-funkčných rozdielov v účinkoch aripiprazolu a kvetiapínu, atypických antipsychotík s podobnými terapeutickými vlastnosťami, ale rozdielnym vplyvom na dopaminergické receptory v mozgu, u experimentálnych zvierat
Program: APVV
Project leader: RNDr. Kiss Alexander DrSc.
Annotation:Antipsychotics (ATs) represent a group of drugs used in the treatment of psychotic and depressive disorders. However, the frequency of ATs treatment is rather increasing than decreasing and the number of new atypical AP drugs have been emerged over the last few years. In addition, APs treatment is connected with a number of unwanted side effects, such as extrapyramidal syndrome, akathisia, body mass increase, agranulocytosis, tardive dyskinesia, somnolencia, etc. Anatomical-functional investigations are incessantly bringing information about the effects of APs on the activity of neurons and their spatial distribution over the whole brain, which allows more precisely to define and predict the consequences of the APs treatments. The aim of the present study is to reveal the effects of the acute and repeated treatment of two, relatively new atypical APS, aripiprazole (ARI) and quetiapine (QUE), on the activity of neurons in the forebrain and extra-forebrain areas of the brain, to identify the phenotype (chemical) character of the targeted neurons, to investigate their impact on the behaviour, and to compare their impact on the activity of signaling pathways, expression of signaling molecules, and secretion of selected neuropeptides in anatomically precisely defined brain structures. The data of the present project will be new and helpful for the deeper understanding of the biology of mental disorders. They also will bring new impulses to the drug developing procedures to make drugs with more directed and beneficial therapeutic efficacy.
Duration: 1.7.2016 - 30.6.2020

Study of biological effects of H2S/NO products and molecular mechanism of their actions
Štúdium biologických účinkov produktov H2S/NO interakcie a molekulárne mechanizmy ich pôsobenia
Program: APVV
Project leader: RNDr. Ondriaš Karol DrSc.
Annotation:Now it is well acknowledged that endogenously produced H2S affects and is involved in regulation of many physiological and pathological functions of living organisms. It is suggested that biological effects of H2S might not result from actions of H2S alone, but from its oxidation products, which come from e.g. interaction of H2S with NO. Last four years, our “international” group indentified the following products of H2S and NO interaction: nitrosopersulfide (SSNO−), polysulfides (HSn−) and dinitrososulfite [N-nitrosohydroxylamine-N-sulfonate (SULFI/NO) (Proc Natl Acad Sci U S A. 112, 2015, E4651-E4660). Biological effects and molecular mechanisms of these products are not completely understood Therefore the aim of our project is to explore biological effects of the products of H2S/NO interactions and to study their molecular mechanism of their actions. Particularly, as a continuation of our research, we will study their effects on rat blood pressure and aortic rings relaxation. To elucidate molecular mechanisms of their biological effects, we will study their influence on expression of enzymes that endogenously produce H2S (CBS, CSE and 3-MST), on intracellular membrane channels, concentration of intracellular calcium, lipid peroxidation and their antioxidant properties. Goal of the project is also to find out, if studied compounds could provide us with information leading to a drug design based on their molecular structure, what could be an object for next application studies and lead to implementation in medical praxis.
Duration: 1.7.2016 - 30.6.2020

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: Mgr. Smolková Božena 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

HYPOMITGEN - -
Štúdium genetických príčin zriedkavých ochorení s dôrazom na metabolické poruchy asociované s hypoglykémiami a poruchy mitochondrií
Program: APVV
Project leader: RNDr. Gašperíková Daniela DrSc.
Duration: 1.8.2018 - 30.6.2022

Study of the mechanisms blocking tumorigenicity of cancer cells overexpressing human tumor necrosis factor alpha.
Štúdium mechanizmov, ktoré eliminujú tumorigenitu nádorových buniek vplyvom nadexpresie ľudského faktoru nádorovej nekrózy.
Program: VEGA
Project leader: RNDr. Tyčiaková Silvia PhD.
Annotation:Tumor necrosis factor alpha (TNFa), a pleiotropic cytokine, can induce apoptosis of tumor cells, modulate expression profile, secretome and can have tumor destructive capacity. As showed our recent studies, engineered human melanoma and colon carcinoma cell lines overexpressing TNFa fail to form tumors in xenografted mice, conferring 100% protection against tumorigenesis. These results gave us an impulse to study mechanisms of TNFa induced blocking of tumorigenicity and its influence on tumor heterogeneity. We will focus on alternation in expression and secretion profile of the tumor cells, especially markers of the stemness/pluripotency and epithelial-mesenchymal transition. We will monitor the impact of TNFa transgene expression on the proportion of subpopulation of CD133+/ALDH+ positive tumor initiating cells (TISc), which are responsible for tumorigenesis, therapy resistance and relapse. Detailed study of the process of TNFa- induced tumor resistance can offer a new therapeutic strategy to eliminate TICs.
Duration: 1.1.2017 - 31.12.2020

The study of gut microbiome in patients with colorectal cancer
Štúdium mikrobiómu u pacientov s kolorektálnym karcinómom
Program: VEGA
Project leader: RNDr. Wachsmannová Lenka PhD.
Annotation:Colorectal cancer is the most frequent malignancy of the digestive tract in Slovakia with the highest incidence worldwide. Therefore, the studies on the causes, risk factors and new possibilities for screening and treatment is highly actual issue. The project aims to characterize bacteria from colorectal adenomas and carcinomas, rectal swabs of cancer patients and compared with the intestinal microflora from healthy people biopsies. To identify differences in the bacterial composition, ENTEROtest will be used. The presence of intracellular bacteria will be monitored by Gentamicin protection assay. Molecular analysis for the genes associated with pathogenicity and adhesion will be done by PCR. Identification and analysis of certain types of microbiota,which are not presented in healthy intestinal tract, but in the precancerous tissue and would correlate with the results obtained from rectal swabs, could provide a simple,non-invasive tool for the assessment of increased risk of colorectal cancer development.
Duration: 1.1.2017 - 31.12.2020

Study of protective potential of synthesized phenylethanoid glycosides in the systems of mammalian cells and plasmid DNA
Štúdium protektívneho potenciálu syntetizovaných fenyletanoidných glykozidov v systémoch cicavčích buniek a plazmidovej DNA
Program: VEGA
Project leader: Mgr. Horváthová Eva PhD.
Annotation:DNA damage associated with different changes at the genetic level of the cell is generally considered as the most important stimulus for the initiation of the multistage process of carcinogenesis. The study of protective effects of natural compounds and their analogs, which are frequently used in health protection and prevention, is therefore of great importance. In the proposed project we plan: 1. to prepare phenylethanoid glycosides and their analogues using chemical or less conventional enzymatic procedures; 2. to determine their antioxidant, chelating and reducing capacity using biochemical methods; 3. in experimental systems utilizing mammalian cells, primary rat hepatocytes and plasmid DNA to evaluate their protective potential against lesions induced by model mutagens and carcinogens; 4. to monitor the activity of important cellular enzymatic and nonenzymatic antioxidants. Compounds studied could be a part of preventive and therapeutic strategies aimed at fighting the civilization diseases.
Duration: 1.1.2016 - 31.12.2019

Study of products of H2S/oxidized glutathione interaction on membrane channels and molecular mechanism of their actions
Štúdium účinkov produktov interakcie H2S/oxidovaný glutatión na membránové kanály a molekulárny mechanizmus ich pôsobenia
Program: VEGA
Project leader: RNDr. Ondriaš Karol DrSc.
Duration: 1.1.2017 - 31.12.2020

TestCure - 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: APVV
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

The effect of GDNF vector and block of inhibition molecules on interneuronal connections and axonal outgrowth after cervical and thoracic spinal cord injury
Účinok GDNF vektora a blokovania inhibičných molekúl na interneuronálne prepojenia a prerastanie axónov po cervikálnom a torakálnom poškodení miechy
Program: VEGA
Project leader: RNDr. Lukáčová Nadežda DrSc.
Annotation:The aim of proposed project is 1) to examine molecular changes in the respiratory nuclei and interneurons, and reinervation of bulsbospinal pathway after cervical compression and application of AAV9-GDNF vector that allow long-term and stable transgene expression of GDNF in the vicinity of the SCI lesion, 2) to promote axonal regeneration and to improve functional recovery after thoracic compression by blocking the signaling pathways for axonal growth inhibitors. We will compare two ways (intraparenchymal and subpial) of application, and in combination with post-traumatic rehabilitation training we will determine, which interneuronal connections (commissural, propriospinal, reticulospinal) promote functional outcome.
Duration: 1.1.2017 - 31.12.2019

The role of ALDH1 in chemoresistance of cancer cells
Úloha ALDH1 v chemorezistencii nádorových buniek
Program: VEGA
Project leader: RNDr. Kozovská Zuzana PhD.
Annotation:The project will be focused on the study of the role of aldehyde dehydrogenase 1 (ALDH1) in chemoresistance and stemness of tumour cells. We will use cell lines derived from human colorectal adenocarcinoma, their chemoresistant derivatives as well as primocultures derived from patients’ tissues. The subject of the study will be cancer stem cells (CSC) which are characterised with higher chemoresistance, and are believed to be the main cause of chemotherapy failure. They represent 0.1-10 % of cancer cell population, depending on cell type and cultivation conditions. We will use the immunomagnetic separation and fluorescently activated cell sorting (FACS) for separation of particular cell population in which we will analyse the expression profile and we will compare it with the expression profile of the rest population. The part of the project will be focused on siRNA and/or shRNA methods by which we will specifically inhibit the expression of genes ALDH1A1 or ALDH1A3 involved in the resistance of CSC.
Duration: 1.1.2017 - 31.12.2020

TUMICAR - The role of CA IX in adaptation to tumor microenvironment and in resistance to anticancer therapy: molecular mechanisms and clinical implications
Úloha CA IX v adaptácii na nádorové mikroprostredie a v rezistencii na protinádorovú terapiu: molekulárne mechanizmy a klinické implikácie
Program: APVV
Project leader: prof. RNDr. Pastoreková Silvia DrSc.
Annotation:The project is based on the most recent understanding of tumor microenvironment as a key factor driving cancer progression and therapy resistance through physiological stresses, such as hypoxia and acidosis, and via paracrine signaling from cells of tumor stroma. In this context, we intend to focus on carbonic anhydrase IX (CA IX), a cancer-associated protein induced by hypoxia and functionally implicated in tumor biology. CA IX has been correlated with aggressive tumor phenotype, poor outcome and unfavorable prognosis of cancer patients, and is considered as a clinically relevant biomarker and promising target for anticancer therapy. The main project goal is to elucidate the role of CA IX in the adaptation of tumor cells to microenvironmental stresses, in the crosstalk between cancer and stromal cells, as well as in the resistance to chemotherapy. Our efforts will be aimed at decoding molecular mechanisms of the anticipated pro-survival and pro-metastatic effects of CA IX in response to drugs and stresses (i.e. involvement in autophagy, senescence or multidrug resistance). We also intend to evaluate immunotherapeutic strategies of targeting CA IX in tumor xenografts by our domain-specific monoclonal antibodies using diverse cell models (acid-adapted, chemotherapy-adapted, expressing CA IX mutants or siRNA). Moreover, we want to shed more light on responses of mesenchymal stromal cells to hypoxia, acidosis and to CA IX ectodomain cleaved from cancer cells. We expect that the project can bring original data contributing to improvement of basic knowledge on tumor biology and to further development of rational diagnostic and therapeutic strategies. Existing research infrastructure, including expertise of participating teams, modern equipment, and unique in-house reagents and models, represent solid prerequisites for the successful accomplishment of the project objectives.
Duration: 1.7.2016 - 30.6.2020

The role of cytokines/chemokines in the immune response to influenza A infection
Úloha cytokínov/chemokínov v imunitnej odpovedi na infekciu vírusom chrípky typu A
Program: VEGA
Project leader: RNDr. Betáková Tatiana DrSc.
Annotation:Multiple factors are likely to influence immune response to influenza A virus (IAV) infection, including the rate of virus replication, its ability to actively antagonise IFN induction and also factors conferred by the host. Innate immune response results in the production of cytokines/chemokines and activation of immune-signaling pathways. NS1 protein of IAV counteracts the induction of antiviral response. Influenza virus NS1 deletion mutants pose great tool for studying innate immune response against influenza virus, especially stimulation individual genes involved in individual cytokines elicit by influenza virus infection. Proteome profiler array and qPCR will allow as study expression more than 40 cytokines and 25 chemokines and their pathways depending of the time after infection. At present, type III IFNs are the least well characterized IFN types. There is some evidence that type III IFNs not only activates the same IFN-signaling pathways as type I IFNs but it also contributes to transcriptional regulation of other genes which are not stimulated by type I IFN. Our preliminary data show that IFN-lambda trigger IFN-signaling pathway without increasing expression of RIG-1 and stimulate induction of type I IFN. Thereby, expression of receptor proteins specific for type I and type III IFNs and activation of RIG-1/MDA5-MAVS-IRF3/7 pathway will be studying in the cells induced by individual IFNs as well as in the cells infected with NS1 deletion mutants, human or avian influenza viruses.
Duration: 1.1.2016 - 31.12.2019

The role of glutamate transporters in blood cells in ischemic tolerance
Úloha glutamátových transportérov krvných buniek v ischemickej tolerancii
Program: VEGA
Project leader: RNDr. Bonová Petra PhD.
Duration: 1.1.2018 - 31.12.2020

The role of myokines and adipokines in improvement of the cardiometabolic parameters following lifestyle changes in sedentary subjects
Úloha myokínov a adipokínov v zlepšení kardiometabolických parametrov pri zmene životného štýlu osôb so sedavým spôsobom života
Program: VEGA
Project leader: MUDr. Rádiková Žofia PhD.
Annotation:Sedentary lifestyle and obesity are very well known cardiometabolic risk factors. Adipose tissue and skeletal muscle produce adipokines and myokines, respectively, acting as hormones and mediating the effects between producing and target organs such as liver and brain. However, their specific role in the improvement of insulin resistance and associated disorders needs to be elucidated. We hypothesize, that specific lifestyle counseling (8-wk of diet with 30% caloric reduction + aerobic exercise 150min/week) in our study will lead to weight loss, reduction in fat mass, improving the physical fitness level and changes in cardiometabolic parameters - lipid profile, insulin sensitivity, blood pressure. The aim of our study is to explore the role of selected adipokines (leptin, resistin, adiponectin) and myokines (irisin, myostatin, myonectin) and of their interrelation in the process of insulin sensitivity improvement, in regard to changes in body composition and cardiomeatbolic parameters studied.
Duration: 1.1.2018 - 31.12.2020

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

The role of vitamin D and interferons type III in gammaherpesvirus oncogenesis
Úloha vitamínu D a interferónov tretieho typu v gamaherpesvírusovej onkogenéze
Program: VEGA
Project leader: RNDr. Režuchová Ingeborg PhD.
Annotation:Human gammaherpesviruses, namely Epstein-Barr virus and Kaposi´s sarcoma-associated herpesvirus, establish life-long latent infection in B cells and are known as causative agents of several malignancies and lymphoproliferative disorders. We have identified that interferons type III (IFNs-III) could play an important role in establishment, maintenance and regulation of gammaherpesvirus latency. Moreover, it is known that vitamin D deficiency is a critical factor in development of several cancers. In our project we hypothesize that a lack of vitamin D in a combination with suppressed immune system could contribute to cell transformation and tumorigenesis. Our ambition is to explore the antiproliferative, antiviral and preventive effect of vitamin D and IFNs-III in gammaherpesvirus-associated cancer cells. We expect that our results will elucidate relation of vitamin D to innate immune system and can be applied to other types of cancer cells, which are characterized by high expression of receptor for IFNs-III.
Duration: 1.1.2016 - 31.12.2019

The virus, the tick, and blood: gene expression analysis of the tick Ixodes ricinus in the context of tick-borne encephalitis virus infection and feeding
Vírus, kliešť a krv: analýza expresie génov kliešťa Ixodes ricinus v kontexte infekcie vírusom kliešťovej encefalitídy a cicania
Program: VEGA
Project leader: RNDr. Fumačová Havlíková Sabína PhD.
Annotation:Tick, Ixodes ricinus, transmits a serious neuroinfection disease caused by tick-borne encephalitis virus (TBEV). Bioactive molecules from the tick salivary glands help not only to tick feeding, but also contribute to the transmission and replication of TBEV. During the tick feeding is regulated expression of a large number of genes. The aim of this project will be further characterization of the previously unstudied group of genes which were identified based on analyzes using the transcription methodology MACE ("Massive Analysis of cDNA Ends") as significantly regulated genes in the context of TBEV infection and feeding on the mice. We obtain their entire genetic sequences using the molecular, immunohistochemical and bioinformatics methods and we observe detail location and function of these genes. The results will contribute to the clarification of the molecular-regulatory mechanisms of TBEV transmission and to the intracellular immunity of tick.
Duration: 1.1.2017 - 31.12.2019

THE EFFECT OF ELECTROMAGNETIC RADIATION DURING PRENATAL DEVELOPMENT OF RATS ON SOME TISSUES AND ORGANS FROM A MORPHOLOGICAL ASPECT
VPLYV ELEKTROMAGNETICKEJ RADIÁCIE POČAS PRENATÁLNEHO VÝVOJA POTKANOV NA NIEKTORÉ TKANIVÁ A ORGÁNY Z MORFOLOGICKÉHO ASPEKTU
Program: VEGA
Project leader: RNDr. Račeková Enikö CSc.
Duration: 1.1.2018 - 31.12.2020

FLAMADIP - Effect of flavonoids and mycotoxins on adipose tissue. The influence of metabolic status, inflammation and oxidative stress
Vplyv flavonoidov a mykotoxínov na tukové tkanivo v závislosti od celkového metabolického stavu, zápalu a oxidačného stresu
Program: APVV
Project leader: Ing. Zorad Štefan CSc.
Annotation:Adipose tissue is metabolic and endocrine organ. Disorders in its functions result in ectopic accumulation of lipids in muscles, liver, pancreas and brain, elevation in parameters of oxidative injury. Reactive oxygen species (ROS) with hyperglycemia initiate inflammation processes in adipocytes. Published works recommend higher consumption of natural substances to improve antioxidant capacity. There is no comprehensive and relevant clinical study proving positive effect of antioxidants on any disease. New theory (Watson, J.D., 2014) introduces that an initiator of diabetes is incapability of organism to create sufficient amount of ROS. Divergent effect of flavonoids and their role as antioxidants/pro-oxidant is discussed. Actual mechanisms of action of flavonoids in vitro were investigated on 3T3-L1 mouse preadipocytes. In our project we consider as relevant to use primary culture of humanpreadipocytes. Publications concerning in vivo effect of lavonoids on metabolism pointed that the effect of these substances is dependent not only on chemical structure but also on kind of animal model. Therefore in our project we will systematically study the effect of selected flavonoids and mycotoxins in healthy animals, obese animals with low level of oxidative stress and diabetic animals with high level of oxidative stress and inflammation. Main aim is to verify if, in literature describing inhibition effect of flavonoids on adipogenesis depend on metabolic disease, if long-term inhibition of adipogenesis has positive impact on metabolism of adipose tissue and organism. Further we will study the role of oxidative stress in mechanism of actions of flavonoids and mycotoxins on adipose tissue from aspect of regulation of glucose and lipids metabolism by insulin cascade. We believe that results of project specify the role of flavonoids in nutrition of livestock and human.
Duration: 1.7.2016 - 30.6.2020

The effect of chronic inflammation on cardiometabolic parameters
Vplyv chronického zápalu na kardiometabolické parametre
Program: VEGA
Project leader: MUDr. Penesová Adela PhD.
Annotation:Systemic chronic inflammation has been proposed to have an important role in the pathogenesis of obesity-related insulin resistance and atherosclerosis. Aim of present study is to elucidate mechanisms involved in the pathogenesis of impaired insulin action in chronic inflammatory diseases such rheumatoid arthritis (RA) and multiple sclerosis (MS). Several metabolic, immune markers, autonomic nervous system dysfunction, physical fitness, endothelial dysfunction, impaired function of microcirculation will be measured in patients SM at the time of diagnosis and after at least of 12 months treatment with biological therapy or crossectionally in RA. Age, sex and BMI matched healthy subjects will be used as control group. We will look for associations between measured parameters, clinical characteristics and effect of the treatment, which may allow us to identify critical mechanisms of IR and cardiometabolic risk in chronic inflammation
Duration: 1.1.2016 - 31.12.2019

Impact of infection with avian influenza virus on secondary bacterial infection
Vplyv infekcie vtáčím vírusom chrípky na vývoj sekundárnej bakteriálnej infekcie
Program: VEGA
Project leader: RNDr. Bobišová Zuzana PhD.
Duration: 1.1.2018 - 31.12.2021

The effect of IRAP (insulin-regulated aminopeptidase) aminopeptidase activity inhibition on metabolism of adipose tissue in obesity and insulin resistance
Vplyv inhibície aminopeptidázovej aktivity iRAP (inzulínom-regulovaná aminopeptidáza) na metabolizmus tukového tkaniva pri obezite a inzulínovej rezistencii
Program: VEGA
Project leader: Ing. Kršková Katarína PhD.
Duration: 1.1.2017 - 31.12.2019

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: APVV
Project leader: prof. RNDr. Pastorek Jaromír DrSc.
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 - 30.6.2020

The impact of tumor microenvironment and therapy on subclonal diversity in MM and WM
Vplyv mikroprostredia a protinádorovej terapie na diverzitu malígnych subklonov v MM a WM
Program: VEGA
Project leader: RNDr. Cholujová Dana PhD.
Duration: 1.1.2017 - 31.12.2019

The effect of selected natural compounds of plant origin (essential oils) on rickettsiae and ticks
Vplyv vybraných sekundárnych rastlinných metabolitov (esenciálne oleje) na rickettsie a kliešte
Program: VEGA
Project leader: Mgr. Štefanidesová Katarína PhD.
Annotation:I. ricinus and D. reticulatus, belonging among the most important vectors of tick-borne diseases (TBD) in Europe may transmit various pathogens, e. g. rickettsiae, anaplasmae, borreliae, C. burnetii, F. tularensis, and babesiae.The only available prevention of the majority of TBD is to avoid a tick bite. Increasing incidence of TBD,occurence of infected ticks in urban and suburban habitats, and possible adverse health effects of synthetic repellents caused tendency to use „natural repellents“ with unknown efficacy. Proposed project aims to clarify the efficacy of essential oils (EO) against ticks (to evaluate the ability of EO to interfere with the host-seeking behaviour) as well as against transmitted pathogens (to evaluate antirickettsial properties of EO). Project will help to elucidate the inhibitory properties of EO against obligate intracellular bacteria, and to assess which of EO may be used as the prevention of tick bite for the part of the population,that decided not to use commercial repellents.
Duration: 1.1.2016 - 31.12.2019

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

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

CATS - 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: APVV
Project leader: prof. Ing. Križanová Oľga DrSc.
Duration: 1.7.2017 - 30.6.2021

MASnPNO - 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: APVV
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

Alterations in neuritogenesis related to neurodevelopment
Zmeny regulácie neuritogenézy vo vzťahu k neurovývinovým ochoreniam
Program: APVV
Project leader: RNDr. Bakoš Ján PhD.
Annotation:Functional development of social skills, speech and memory is determined by formation of neural circuits under the control of many genes and epigenetic factors. At the cellular and molecular level, they include regulation of neurite outgrowth (axons, dendrites) and changes of neurite direction. Oxytocin production, secretion and receptor activation is frequently associated with neurodevelopmental disorders, including autistic spectrum diseases. Therefore, it is important to understand the role of oxytocin in regulation of neuritogenesis and neurite outgrowth. It is not known, how oxytocin receptor activation is related to the changes of neurite elongation and how oxytocin interacts with other factors, particularly cytoskeletal proteins and GTPases, their disruption suppose to play a role in neurodevelopmental disorders. Central aim of the project is to search for interaction of oxytocin with cytoskeletal proteins MAGEL2 and SHANK3 in relation to neuritogenesis. The main hypothesis represents an assumption, that oxytocin can compensate neuritogenesis disrupted by downregulation/knockout of MAGEL2 and SHANK3 genes. The project includes manipulation of MAGEL2 and SHANK3 genes and their consequences on neuritogenesis. Efforts will be devoted to visualize neurite elongation in real time and to find an association between oxytocin levels and neuritogenesis. Systematic approach to research of regulation of neuronal cell growth and neurite arborisation may bring important data for understanding of brain development at the molecular level and contribute to reveal causes of neurodevelopmental disorders.
Duration: 1.7.2016 - 31.12.2019

Projects total: 137