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Biomedical Research Center SAS

International projects

DevelopAKUre - FP7 Health: Clinical Development of Nitisinone for Alkaptonuria
7RP Zdravie: Klinický vývoj Nitisinonu pre Alkaptonúriu
Program: 7RP
Project leader: Mgr. Zaťková Andrea PhD.
Annotation:DevelopAKUre is a proposal to fund the clinical development of an orphan designated drug, nitisinone, for the treatment of a rare Mendelian disease, Alkaptonuria (AKU). AKU is a genetic deficiency of homogentisic acid dioxygenase, causing high levels of homogentisic acid (HGA). Oxidation of HGA to pigment polymer, termed ochronosis, alters connective tissues. This leads to multisystemic damage dominated by premature severe arthritis. Currently, multiple arthroplasty is inevitable since AKU is incurable and there is no effective palliative therapy. No data exists regarding the presence or absence of ochronosis before age 30 years. Hence, it is unknown whether treatment is necessary before then. A potential HGA-lowering therapy with nitisinone is available, but lacks outcome data. Thanks to our existing successful fundamental and clinical research (cell models, animal models, natural history studies), we are now ready for the final stage of clinical development of nitisinone for AKU in order to overcome these challenges. This will involve a dose finding study, a phase 3 clinical trial to prove efficacy, and a cross-sectional study in children and young adults to determine when to start treatment. The results of DevelopAKUre will allow us to make the case to the European Medicines Agency for marketing authorisation of nitisinone for AKU, thereby contributing to the goal of the International Rare Diseases Research Consortium of 200 new therapies by 2020. Our consortium has worked together for five years already. It includes Liverpool Universitys AKU Research Team as the lead applicant, the AKU Society UK patient group for dissemination and patient recruitment, three SMEs (Denmark, Netherlands) for biomarker analysis and clinical trial coordination, an industry partner (Sweden) supplying the drug and regulatory support, three universities (UK, Italy, Slovakia) for the analysis of data, and three clinical trial centres (UK, France, Slovakia) to reach required numbers.
Project web page:http://cordis.europa.eu/project/rcn/106157_en.html
Duration: 1.11.2012 - 31.1.2019

CAPSID - Wissenschaftliche Kapazitätsbildung in biomedizinischer Forschung durch wissenschaftlichen Austausch und gemeinsame Entwicklung von Forschungsservices
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:Die grenzübergreifende Region zwischen den Hauptstädten Wien - Bratislava charakterisiert sich durch eine hohe Anzahl an Universitäten und Forschungseinrichtungen. Nur wenige dieser Institutionen haben eine starke internationale Reputation im Bereich biomedizinische Wissenschaften und es gibt immer noch ein niedriges Level an wissensintensiven Services. Mit diesem Projekt werden beide Herausforderungen angesprochen werden, da internationale Wissenschaftler in die Region gebracht werden, die Fortbildungsmöglichkeiten erhöht werden und neue Expertise entwickelt sowie neue wissensintensive Services in der Produktion von biomedizinisch relevanten Proteinen erarbeitet werden. Die Aktivitäten inkludieren ein gemeinsames Wissenschaftsprojekt um eine neue Serviceplattform zu entwickeln, ein Open Access Projekt, Fortbildungsmöglichkeiten durch Besuche internationaler Wissenschaftler, 1 Konferenz und 3 wissenschaftliche Workshops. Die Aktivitäten werden für Universitäten und Forschungsinstitute angeboten, aber auch für in der Region angesiedelte Biotechfirmen und Start-Ups zur Verfügung stehen. Alle Aktivitäten werden gemeinsam in Wien und Bratislava umgesetzt. Individuelle Projektziele sind i) wissenschaftliche Netzwerke und internationale Sichtbarkeit der teilnehmenden Institutionen zu verbessern, messbar durch die Anzahl der Teilnehmer an Networkingevents und Trainings, ii) Etablierung von Langzeitkollaborationen zwischen Partnern, messbar durch die Anzahl der Forschungsorganisationen die am Projekt teilnehmen, iii) Entwicklung neues Wissens und Expertise für beide Partner, messbar durch die Entwicklung der Forschungsplattform. Der Langzeitnutzen dieses Projektes ist Vermehrung des grenzübergreifenden Wissenstransfers und Wissenschaftskooperationen, Erhöhung des Innovationspotential der Region durch Wissenschaftsservice und Expertise und Steigerung der Attraktivität der Region für hoch qualifizierte internationale Wissenschaftler durch verbesserten wissenschaftlichen Austausch und Sichtbarkeit.
Duration: 1.7.2018 - 31.12.2021

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

Effects of vortioxetine in the tryptophan-depletion model of SSRI-resistant depression in female rats
Efekt vortioxetínu v SSRI-rezistentom modeli depresie založenom na tryptofánovej deplécii u samíc potkanov
Program: Iné
Project leader: prof. PharmDr. Ježová Daniela DrSc.
Duration: 1.7.2014 - 31.12.2018

EVAg - European virus archive goes global.
Európsky vírusový archív sa stáva globálnym.
Program: Horizont 2020
Project leader: RNDr. Klempa Boris DrSc.
Project web page:http://global.european-virus-archive.com/
Duration: 1.4.2015 - 31.3.2019

Characterization of the molecular mechanisms that modulate GPM6A-­induced filopodium formation during chronic stress exposure
Charakterizácia molekulárnych mechanizmov zmien GPM6A počas chronického stresu
Program: Medziakademická dohoda (MAD)
Project leader: prof. PharmDr. Ježová Daniela DrSc.
Duration: 1.1.2017 - 31.12.2018

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

intraMMclo - Multiple myeloma intra-clonal heterogeneity: evolution and implications of targeted therapy
Intraklonálna heterogenita v mnohopočetnom myelóme: evolúcia a implikácie pre cielenú liečbu
Program: ERANET
Project leader: RNDr. Jakubíková Jana PhD.
Annotation:The overall objective of this proposal is to investigate evolution of intra-clonal heterogeneity during the development and progression of MM by combining cellular, molecular, and genetic approaches. Moreover, defining the impact of chemotherapy and/or immunotherapy on intra-clonal selection, together with the role of the tumor microenvironment on clonal dynamics on the level of genetic and cellular complexity, will provide the framework for development of novel personalized diagnostic criteria that will lead to more effective therapeutic strategies. Our emphasize will focus on the process of clonal evolution during the development of MM: from premalignant precursor conditions known as MGUS and smoldering MM without clinical manifestations of diseases but with present cytogenetic and/or gene-expression abnormalities to active disease stages. Moreover, we will evaluate the impact of novel chemotherapy/immunotherapy on the dynamic nature of the clonal selection in MM in our ongoing clinical trials, either alone or together with other conventional anti-MM therapies, delineating their ability to prevent recurrence of subclones and resistance to therapy. Furthermore, the role of the tumor microenvironment by characterizing the impact of overall host immunity on clonal selection will be defined.
Duration: 1.7.2016 - 30.6.2019

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

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

Neuroprotective potential of cryopreserved placental mesenchymal stem cells (MSCs), extract, cord blood serum in the spinal cord injury (SCI).
Neuroprotektívne 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

Targeting molecular pathways of glycolipotoxicity by a novel carboxymethylated mercaptotriazinoindole inhibitor of aldo-keto reductase AKR1B1 in diabetes, inflammation and age-related neurodegeneration.
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Program: Bilaterálne - iné
Project leader: RNDr. Račeková Enikö CSc.
Duration: 15.4.2016 - 15.4.2019

Vesicular glutamate transporter 3 knockout mice and changes in gene expression of the transporter: relation to stress hormones, behavior and animal models of mood disorders
Vezikulárny glutamátový transportér a zmeny v jeho génovej expresii: vzťah k stresovým hormónom, správaniu a animálnym modelom psychických porúch
Program: Medziakademická dohoda (MAD)
Project leader: prof. PharmDr. Ježová Daniela DrSc.
Duration: 1.1.2016 - 31.12.2018

HISENTS - High level Integrated Sensor for Nano Toxicity Screening
Vysokointegrovany senzor na skrining nanotoxicity
Program: Horizont 2020
Project leader: RNDr. Gábelová Alena CSc.
Annotation:The HISENTS vision is to address the problem of the dearth of high-quality tools for nano-safety assessment by introducing an innovative multimodular high throughput screening (HTP) platform including a set of individual modules each representing a critical physiological function connected and integrated in a hierarchical vectorial manner by a microfluidic network. The increase of the capacity to perform nano-safety assessment will be realised by innovative instrumentation developments for HTP and high content analysis (HCA) approaches. Toxicogenomics on chip is also one embedded objective. Our interdisciplinary approach focuses on tools to maximise the read-across and to assess applicable endpoints for advanced risk assessment of nanomaterials (NM). The main goal is thus to establish individual chip-based microfluidic tools as devices for (nano)toxicity screening which can be combined as an online HTP platform. Seven different chip-based sensor elements will be developed and hierarchically combined via a flow system to characterise toxicity pathways of NM. The HISENTS platform allows the grouping and identifying of NM. Parallel to the screening, the pathway and interaction of NM in biological organisms will be simulated using the physiologically based pharmacokinetic (PBPK) model. Using the different sensor modules from the molecular to cell to organ level, HISENTS can input quantitative parameters into the PBPK model resulting in an effective pathway analysis for NM and other critical compounds. The developed platform is crucial for realistic nano-safety assessment and will also find extensive application in pharmaceutical screening due to the flexible modifications of the HTP platform. The specific objective is the development of a multimodular HTP platform as new a screening tool for enhancing the efficiency of hazard profiling. Currently, no such flexible, easy-to-use screening platform with flexibly combinable chip-based sensors is available on the market.
Duration: 1.4.2016 - 31.3.2019

Endurance Training and/or administration of neurotrophic factor as a novel therapeutic approach for treatment of Spinal Cord Injury
Vytrvalostný tréning a/alebo aplikácia rastových faktorov ako nové terapeutické prístupy v liečbe miechy po jej poranení
Program: Medziakademická dohoda (MAD)
Project leader: RNDr. Lukáčová Nadežda DrSc.
Annotation:Neurotrophic factors (NF) are known to mediate the effect of physical activity on neurogenesis and motor function. Our working hypothesis is that endurance training and/or the administration of NF into selected spinal cord regions after spinal cord injury will enhance the level of NF and improve functional recovery after spinal trauma. While the levels of NF and their receptors are spontaneously down regulated at the site of injury, we anticipate that endurance training enhance the expression of NF and their receptors in motoneurons of spinal cord.
Duration: 1.1.2016 - 31.12.2018

DIVAS - Application of next generation sequencing for the study and diagnosis of plant viral diseases in agriculture
Využitie sekvenovania novej generácie pre štúdium a diagnostiku vírusových chorôb rastlín v poľnohospodárstve
Program: COST
Project leader: Ing. Glasa Miroslav DrSc.
Duration: 9.3.2015 - 8.3.2019

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

Relationship between changes of oxytocin levels and brain development
Vzťah medzi zmenami hladín oxytocínu a vývinom mozgu
Program: Medziakademická dohoda (MAD)
Project leader: RNDr. Bakoš Ján PhD.
Duration: 1.1.2016 - 31.12.2018


National projects

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

AMICIS - Prognostic biomarker for colorectal carcinoma based on miRNA analysis and characterization of selected proteins in the circadian context
Analýza mikroRNA a charakterizácia expresie vybraných proteínov v cirkadiánnom kontexte ako prognostický biomarker pre kolorektálny karcinóm
Program: APVV
Project leader: RNDr. Sedlák Ján DrSc.
Annotation:The project will analyze the miRNA profiles of peripheral blood exosomes and immunoscore of tumor tissue for their correlation with clinico-pathological data for the assessment of potential biomarker. miRNA profiling will be focused to identification of miRNA expression patterns that have the potential to regulate epigenetic gene regulation and circadian rhythm.
Duration: 1.7.2015 - 30.6.2019

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

BIOGLYCO - Biochips and biosensors for glycorecognition, their development, prepararion and application in cancer research
Biočipy a biosenzory pre glykorozpoznávanie, ich vývoj, príprava a využitie pri výskume rakoviny
Program: APVV
Project leader: Mgr. Švastová Eliška PhD.
Annotation:Due to the rapid development of new technologies is placed a considerable emphasis on their use for improving the quality of life. The most important areas here include the care of human health, such as the fight against cancer. Here is a keen interest in new sensitive diagnostic approaches and technologies to help increase the effectiveness of therapy and cancer research. Development and application of new diagnostic procedures and methods is based in no small measure on the knowledge gained in the basic research in the field of analytical tools based on the biochips and biosensors. The aim of the project is the development and preparation of new analytical glyco-recognizing biochip and biosensor systems based on lectin in different formats in combination with multiple platforms and innovative detection methods, their validation and use in the analysis of real samples in cancer research. The selected design of biochips and used detection platform enable highly sensitive and high-throughput analysis of glycosylation changes, and the involvement of mass spectrometry also accurate identification of glycan structures subject to glycosylation changes. To increase the functionality of biochips will be in the development of analytical systems used also nanotechnology tools, particularly in the preparation of nanostructured surfaces of biochips and for improving the efficiency of detection. Various types of biological samples will be analyzed such as serum, lysates, tissue and isolated glycoproteins from some areas of cancer research (effect of hypoxia, resistance to cytostatics, search of glyco-biomarkers). It is expected that the involvement of the entire spectrum of analytical procedures for glycorecognition developed in this project will help formulate more sophisticated conclusions on the role of glycans in cancer.
Duration: 1.7.2015 - 30.6.2019

The biological effects of the environment with reduced deuterium (D) content or increased pH and physical exercise in relation to cancer: implications for tertiary prevention.
Biologické účinky prostredia so zníženým množstvom deutéria alebo zvýšeným pH a fyzického cvičenia vo vzťahu k onkologickým ochoreniam: implikácie pre terciárnu prevenciu.
Program: VEGA
Project leader: RNDr. Hunáková Ľuba CSc.
Annotation:The project deals with the possibility of the extracellular milieu modulation with potential impact on tertiary prevention of cancer. In vitro we want to examine the regulatory effect of the media with lower deuterium (D) content, or increased pH on the proliferation activity and viability of normal and tumor cells. These will be pursued by various culture and imaging techniques. We will also study possible changes in genome stability by monitoring the incidence of micronuclei typical for cells with replication stress, leading to the increased heterogeneity of tumor population, as well as changes in the expression of surface antigens affecting immune responses, changes in the release of exosomes and in migration of tumor cells. At the level of the human body we want to examine the effects of interventions that modulate the internal environment (Pilates exercise, drinking of alkaline water with reduced ORP) to the redox status, immunological and regulatory body's responses supporting protection against cancer
Duration: 1.1.2016 - 31.12.2018

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

CAMYS - Cytoarchitecture of calcium signalling of cardiac myocytes in development of myocardial hypertrophy
Cytoarchitektúra vápnikovej signalizácie srdcových myocytov vo vývoji hypertrofie myokardu
Program: APVV
Project leader: Ing. Zahradníková Alexandra DrSc.
Annotation:In early phases of many cardiovascular diseases, calcium signalling deteriorates and cardiomyocyte hypertrophy is activated. Calcium signalling, in addition to control of contractile function, modulates many of signalling pathways and metabolism of myocytes. Therefore, disruption of calcium signalling in either systolic or diastolic phase may be a consequence, but also the cause of the maladaptive reaction of myocytes to overload. We hypothesize that processes related to hypertrophy lead to changes in distribution of endo/sarcoplasmic reticulum elements responsible for calcium signalling and for proteosynthesis, and to associated changes in expression and distribution of calcium signalling proteins. This study aims to determine differences in the myocyte calcium signalling system of myocardium adapting to pathological or physiological load and to compare them with development of the myocyte calcium signalling system during postnatal maturation of myocardium. The status of the calcium signalling system will be analysed in models of myocardial load in laboratory rats: a/ sedentary model - animals in standard cages, b/ model of physiological load - animals in cages with a running wheel, 3/ model of pressure overload - surgical obstruction of ascending aorta, and d/ growth model of hypertrophy - postnatal development of myocardium. State-of-the-art methods of electrophysiology, molecular biology and ultrastructural microscopy will be used to characterize quality and distribution of calcium signals, the extent and distribution of smooth and rough sarcoplasmic reticulum, and of expression, localization and co-localization of calcium signalling proteins. We expect that the multidisciplinary approach supported by the expertise of team members will allow interpreting cellular and molecular mechanisms of calcium signalling and drawing conclusions relevant to understanding mechanisms of heart failure that will aid development of new therapeutic and preventative procedures.
Project web page:http://www.umfg.sav.sk/ovsb/projektyovsb/aktivne-projekty-v-ovsb/apvv-15-0302/
Duration: 1.7.2016 - 30.6.2019

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.
Duration: 1.1.2017 - 31.12.2019

DNA methylation profiles in genes associated with breast cancer metasasising
DNA metylačné profily v génoch asociovaných s metastázovaním karcinómov prsníka
Program: VEGA
Project leader: RNDr. Fridrichová Ivana CSc.
Annotation:More than 25% of breast cancer patients develop metastatic disease that represent the main cause of high mortality. The epigenetic changes in tumorigenesis have been intensively investigated and new knowledge in metastatic process could contribute to the improving of advanced disease management and identifying of the new therapeutic targets. In present project, we will evaluate the DNA methylation levels in genes associated with cell-cell adhesion (ADAM23, CXCL12), degradation of basement membrane and extracellular matrix (uPA) and regulation of the epithelial-mesenchymal transition (TWIST, SNAI1 a SNAI2) in 50 invasive breast cancer patients with metastatic lymph nodes. Quantitative analyses of DNA methylation in peripheral blood samples, tumour tissues, positive lymph nodes and circulating tumour cells allow to evaluate the role of specific methylation profiles in partial processes of invasivity and metastasising and clinical utility for metastatic potential monitoring.
Duration: 1.1.2015 - 31.12.2018

DANOMICS - Danube meets omics
Dunaj spája omiky
Program: APVV
Project leader: Ing. Škultéty Ľudovít DrSc.
Annotation:he proposed project Danube meets omics (DANOMICS) was designed to solve the problems related to the low level of cooperation between the scientific institutions in the region, to facilitate the information exchange and to increase the application of omics approach in the research. Scientific institutions from Austria, Slovakia, Serbia and Czech Republic will create the seed for the open laboratory concept in the region and will organize a series of training courses from various omics approaches for young research workers. Moreover, the partners in this project will design the online platform for information exchange, where the improved and/or just developed omics methodology will be posted prior publication in international journals. DANOMICS will, thus, facilitate the scientific work using omics technology, improve the skills of young researchers and increase the knowledge level in the Danube region and better exploit the existing research infrastructure for common research projects.
Duration: 1.1.2017 - 31.12.2018

Mitochondrial dynamics and morphology in transgenic model of Wolfram syndrome: emerging role for heart protection
Dynamika a morfológia mitochondrií u transgénneho modelu Wolframovho syndrómu: význam pre ochranu srdca
Program: VEGA
Project leader: RNDr. Cagalinec Michal PhD.
Annotation:Wolfram syndrome (WS) is a recessive neurological disorder caused by mutation of the Wfs1 gene. The Wfs1 protein is highly expressed in the brain and heart and is embedded in the endoplasmic reticulum (ER) where it modulates Ca2+ levels and ER stress. Additionally, the main symptoms of the WS are consistent with the ones characteristic for mitochondrial diseases. In fact, our preliminary results showed already that silencing of Wfs1 in mouse neurons decreased the mitochondrial fusion frequency and caused mitochondrial fragmentation, demonstrating strong impact of Wfs1 to mitochondrial function in neurons. Although the high expression of Wfs1 in the heart and cardiac symptoms in WS identified recently emphasize the functional importance of Wfs1 in the heart, the most common causes of morbidity in WS are the neurological manifestations.
Duration: 1.1.2016 - 31.12.2018

Effective diagnostics of viruses threatening the production of tomato in Slovakia
Efektívna diagnostika vírusov ohrozujúcich produkciu rajčiaka jedlého na Slovensku
Program: APVV
Project leader: Ing. Glasa Miroslav DrSc.
Duration: 1.7.2015 - 30.6.2019

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

Tick - The role of neuropeptides and receptors in regulation of pathogen transfer from ticks to their hosts
Funkcia neuropeptidov and ich receptorov pri regulácii prenosu patogénov z kliešťov na hostiteľa
Program: APVV
Project leader: Mgr. Špitalská Eva PhD.
Annotation:Ticks are very important vectors of dangerous pathogens, but regulatory mechanisms required for their successful transmission into the host are poorly understood. Likewise, physiological processes controlling function of the salivary glands, gut and gonads during their life cycle have not been elucidated. Our published and preliminary data indicate that several specific peptidergic neurons innervate these organs which are the most important reservoirs of pathogens. Our unpublished experiments suggest that identified neurons control activity of these organs and associated transmission of pathogens during tick feeding on the host. In this project we will use a combination of techniques (immunohistochemistry, molecular biology and bioinformatics) to identify regulatory molecules (neuropeptide and their receptors) and neuronal pathways important for normal function of the salivary glands, digestive system and reproductive organs of the ticks Ixodes ricinus and I. scapularis. We also propose to study the role of specific neuropeptides and their receptors in transmission of pathogens (Rickettsia helvetica and Borrelia burgdorferi) from these tick organs into laboratory mice using RNAi techniques. Expected results may provide tools for effective suppression of pathogen transmission and development of procedures to inhibit reproductive capability of ticks as dangerous ectoparasites of humans and animals.
Duration: 1.7.2015 - 30.6.2019

Mitochondria-endoplasmic reticulum functional interplay in Wolfram Syndrome: emerging role for heart and brain protection
Funkčné prepojenie mitochondrií a endoplazmatického retikula u Wolframovho syndrómu: predpokladaný význam pre ochranu mozgu a srdca
Program: SASPRO
Project leader: RNDr. Cagalinec Michal PhD.
Annotation:Wolfram syndrome (WS)is a recessive neurological disorder caused by mutation of the Wfs1 gene. The Wfs1 protein is highly expressed in the brain and heart and is embedded in the endoplasmic reticulum (ER) where it modulates Ca2+ levels and ER stress. Additionally, the main symptoms of the WSare consistent with the ones characteristic for mitochondrial diseases. In fact, our preliminary results showed already that silencing of Wfs1 in mouse neurons decreased the mitochondrial fusion frequency and caused mitochondrial fragmentation, demonstrating strong impact of Wfs1 to mitochondrial function in neurons. Although the high expression of Wfs1 in the heart and cardiac symptoms in WS identified recently emphasize the functional importance of Wfs1 in the heart, the most common causes of morbidity in WS are the neurological manifestations. How is it possible that mutations of Wfs1 causing significant perturbations in the brain functions are not so prominent in the heart? One explanation of this tissue specificity is that a mechanism compensating for loss of Wfs1 protein function is present in the heart but not in neurons.
Project web page:http://www.confolab.sav.sk/indexSASPRO.html
Duration: 1.3.2015 - 31.12.2018

Fusion activity of influenza A haemagglutinin as a factor of virulence and pathogenicity.
Fuzogénna aktivita hemaglutinínu vírusu chrípky A ako faktor virulencie a patogenity .
Program: VEGA
Project leader: RNDr. Varečková Eva DrSc.
Annotation:Influenza A viruses (IAV) pose a pandemic threat for humans. There is an effort to know their properties on molecular level which allow to predict danger of new emerged IAV in human population. Many factors influencing IAV virulence of both viral and host origin were decribed till now. A potential critical factor is the fusion activity of IAV, which is crucial for the virus entry into the cell and decides about ability of virus to replicate in the host. The role of surface glycoprotein haemagglutinin (HA), in addition to receptor binding, is to mediate fusion of virus and endosomal membranes. Following endocytosis, fusion potential of native HA trimer is activated by low pH in endosomes resulting in HA refolding into the fusion active form. The HA activation is determined by its 3-Dstructure, is pH-dependent, irreversible and virus specific. Aim of our project is to study the correlation between fusion properties of HA and IAV pathogenicity of various subtype, which has not yet been characterized.
Duration: 1.1.2015 - 31.12.2018

GONanoplatform - Graphene - based nanoplatform for detection of cancer
Grafénová nanoplatforma na detekciu rakoviny
Program: APVV
Project leader: prof. RNDr. Pastoreková Silvia DrSc.
Annotation:This project proposal reflects current technological progress and new opportunities in biomedical applications of graphene - based sensors. Our main goals include the design and development of a graphene oxide multifunctional nanoplatform (GO - MFN ) for the detection of tumor cells. In the first step, the development of graphene oxide nanoflakes of appropriate size functionalized by monoclonal antibody is planned. For sensing the tumor cells, GO - MFN of 100 nm size able to interact with a single cell will be prepared. Magnetic nanoparticles added to GO - MFN will enable the inspection of deep tissues by nuclear magnetic resonance. The degree of oxidation of GO, type of the functional groups, optimal functionalization with covalently bound monoclonal ant ibodies and magnetic nanoparticles, are the most important technological steps. The analysis of the basic interactions related to tumor sensing will be conducted in vitro on 2D and 3D cell models up to the proof - of - principle stage that will be directly app licable to laboratory and preclinical testing. The GO - MFN interaction with the cell membrane and with the cell interior will be analysed with subcellular resolution. Such an approach will bring original knowledge and a detailed understanding of the tumor s ensing process that is important for the optimization of the sensor sensitivity. Detection of biomolecules bound to GO - MFN will be addressed in real time by several techniques. The project is based on a complex multidisciplinary approach, ranging from phys ics and chemistry up to biomedicine and combining excellent science and the most sophisticated nano and bio - engineering. The involved partners possess key skills, infrastructure, antibodies and tumor models, and are highly motivated to reach the project go als.
Duration: 1.7.2015 - 30.6.2019

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

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

Identifikacion of a molecular mechanism inducing appearance of dormant cell population in multiple myeloma
Identifikácia molekulárneho mechanizmu indukujúceho vznik dormantnej bunkovej populácie u mnohopočetného myelómu.
Program: VEGA
Project leader: RNDr. Bízik Jozef DrSc.
Annotation:Cancer research provided clear evidences that stroma plays a crucial role in progression of hematological malignancies. Recent studies performed by our team showed that the interactions between stromal cells derived from skin and the leukemic cells are reciprocal and very complex. Remarkably, we observed that diverse types of leukemic cells are capable to modulate a reactivity of the stromal microenvironment, e.g. inflammation. However, we have also found out that certain human multiple myeloma cells responded by growth arrest and phenotypic shift to sterile inflammation induced in a three dimensional structure composed of skin stromal cells. Clinical significance of our observation outlines a fact that we have detected in a preliminary study a subclone of cells exhibiting a novel phenotype in >60% of myeloma patients. Therefore, we plan in the proposed project to perform precise analysis and molecular characterization of a phenomenon of multiple myeloma dormancy and its role in manifestation of the disease.
Duration: 1.1.2016 - 31.12.2018

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

ISEPK - Identification of substrates of essential protein kinases using shokat mutants
Identifikácia substrátov esenciálnych proteínkináz využitím shokat mutantov
Program: SASPRO
Project leader: Ing. Čipák Ľuboš PhD.
Annotation:Genomic instability is defined as a process prone to genomic changes or an increased propensity for genomic alterations. The ultimate goal of cell division for most cells is to accurately duplicate the genome and then evenly divide the duplicated genome into the daughter cells or into the germ cells. Alterations or abnormally high-frequency of errors during processes involved in cell division, such as splicing, sister chromatid cohesion, kinetochore assembly and attachment, chromosome segregation or cytokinesis would cause missegregation of chromatids and chromosomal instability. The complexity of cell division is pointing out that this process is controlled by multi-level regulatory network. Several lines of evidence demonstrated that posttranslational modifications of proteins by phosphorylation play important role in regulation of protein functions. However, we still have little clue which protein kinases regulate proteins involved in processes of cell division. So, identification of relevant protein kinases and characterization of biological significance of their activities is highly desirable. Proposed project is aimed to identify direct targets of essential protein kinases and characterize functional relevance of phosphorylation of target proteins for regulation of splicing and fidelity of chromosome segregation by combining the power of analog-sensitive alleles of essential protein kinases with affinity purification and mass spectrometry approaches. The project will provide a new framework for our understanding of how are splicing and chromosome segregation regulated by phosphorylation and will lay the groundwork for future studies. Since the basic cell cycle machinery is highly conserved from yeast to man, it is likely that processes governing in yeast will guide the way for studies of these processes in higher eukaryotes, including humans.
Duration: 1.4.2015 - 31.12.2018

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

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

IMMUNOVIROLOGICS - IMMUNOVIROLOGICS: Immune modulation by HCMV and its immunotherapeutic potential.
IMUNOVIROLOGIKÁ: Imunomodulácia HCMV a jej imunoterapeutický potenciál.
Program: SASPRO
Project leader: Mgr. Nemčovičová Ivana PhD.
Annotation: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. Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that persistently infects the majority of the world’s population. HCMV is a paradigm for viral immune evasion that maintains a number of immunomodulatory genes that act to suppress Natural Killer (NK) cell function. 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 - 31.12.2018

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

Interaction of nitrergic, neurotrophic and endocrine signaling in the etiopathogenesis of schizophrenia
Interakcia nitrergickej, neurotrofickej a endokrinnej signalizácie v etiopatogenéze schizofrénie
Program: APVV
Project leader: prof. PharmDr. Ježová Daniela DrSc.
Duration: 1.7.2015 - 30.6.2019

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

The clinical significance of the relationship between aldosterone and depression and the regulatory mechanisms involved
Klinický význam vzťahu aldosterónu k depresii a zúčastnené regulačné mechanizmy
Program: VEGA
Project leader: prof. PharmDr. Ježová Daniela DrSc.
Duration: 1.1.2015 - 31.12.2018

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

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

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 - 30.6.2019

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 klinicky 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

Molecular pathways influenced by CA IX in hypoxic cancer cell lines
Molekulové dráhy regulované karbonickou anhydrázou IX v hypoxických nádorových bunkách
Program: VEGA
Project leader: MVDr. Kopáček Juraj DrSc.
Annotation:The main object of our study, carbonic anhydrase IX (CA IX) is a transmembrane enzyme expressed predominantly in tumors derived from various tissues and organs. CA IX is markedly induced by hypoxia and its pH regulating activity contributes to overall cancer phenotype. Thus, CA IX can be seen as a marker of hypoxia, a very common feature of solid tumors, as well as a promising therapeutic target in particular carcinomas. Our goal is to uncover signaling pathways and events which contribute to CA IX related cancer outcome and can be seen as putative vulnerabilities. To gain even better comprehension of processes taking place behind we want to harness CRISPR/Cas9 genome editing tool as well. Because of targeted modifications to genes in their natural genomic context, novel systems like CRISPR/Cas9 editing in vivo can lead to establishment of more natural models of cancer and hypoxia and thus, generally can bring deeper understanding of studied phenomena.
Duration: 1.1.2015 - 31.12.2018

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

Possible dual function of P-glycoprotein in leukemia cells: efflux pump and regulatory protein
Možná duálna funkcia P-glykoproteínu pri viacliekovej rezistencii leukemických buniek: efluxná pumpa a regulačný proteín
Program: APVV
Project leader: Ing. Brtko Július DrSc.
Duration: 1.7.2015 - 31.12.2018

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

Neuroendocrine effects on synaptogenesis during the brain development
Neuroendokrinné vplyvy na synaptogenézu v priebehu vývinu mozgu
Program: VEGA
Project leader: RNDr. Bakoš Ján PhD.
Annotation:Although there is no consensus on description and explanation of the mechanisms how synaptic connections are formed, several families of synaptic proteins have been identified bridging a space between presynaptic and postsynaptic neuron membranes. Development of the brain and formation of synapses is under control of many factors, among them hormones – neuropeptides and steroids. Particularly. oxytocin deficit, or alterations in oxytocin signaling might be involved in the pathogenesis of the neurodevelopmental disorder. Therefore, there is urgent need to understand how oxytocin and steroids interact to affect synaptogenesis and expression of synaptic proteins. In the present project, we focus on analyzes of the morphology of the neurons and visualization of the synaptic proteins in response to oxytocin, testosterone or estradiol treatment. Systematic approach to research of regulation of synaptic proteins may bring important data for understanding of the brain development at the molecular level.
Duration: 1.1.2016 - 31.12.2018

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

Neuroprotective mechanisms of the AT2 receptor stimulation after traumatic spinal cord injury.
Neuroprotektívne mechanizmy zahrnuté v stimulácii AT2 receptora po traumatickom poškodení miechy.
Program: VEGA
Project leader: RNDr. Pavel Jaroslav PhD.
Annotation:There is a prolonged social as well as medical demand on intensive research, because no effective and trustworthy clinical treatment for patients with the spinal cord injury (SCI). Since most of the physiological and pathological effects of the Angiotensin II are mediated through the AT1 receptor stimulation, the AT2 receptor study was until recently at the periphery of scientific interest. At present, the AT2 receptor represents a potentially important area of investigation with possible therapeutic application since it was shown its wide neuroprotective potential. Our main objective is to contribute to the elucidation of the neuroprotective mechanisms in which the AT2 receptor plays an important role.
Duration: 1.1.2016 - 31.12.2018

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

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

rick - A new perspective on the effect of rickettsia and Coxiella burnetii in cancerous diseases and neuropathies.
Nový pohľad na účinok rickettsií a Coxiella burnetii pri rakovinových ochoreniach a neuropatiách.
Program: VEGA
Project leader: RNDr. Sekeyová Zuzana PhD.
Annotation:The unveiling of the causal role, of bacterial infection, in the pathophysiology of neuropathy or tumor growth is a challenging task. Several data are referred to in the literature, suggesting synergistic viral and bacterial infections on the human body. This is especially true for the pathogens with an unclear, undefined way of disease developing. Viruses and bacteria are often considered to be the "triggers" of countless serious maladies. We would like to designate a neuropathological patterns, disorders and syndromes, in cancer, cerebrocortical and neoplastic cells (from rat or mice), which may occur due to rickettsial and/or Coxiella burnetii infection. However, we care not only about the causal but also potentially therapeutic context. A panel of human cancerous cell lines will be used with the aim to show the affinity, contact and interaction between a chemotherapeutic treatment of tumors, with “neo-adjuvant” system based on C. burnetii endotoxins, and a surface receptors.
Project web page:https://www.minedu.sk/data/att/12541.pdf
Duration: 1.1.2018 - 30.12.2021

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

METASCA(IX) - Elucidation of novel pro-metastatic functions of tumor-associated carbonic anhydrase IX and its cross-talk with pro-inflammatory response
Objasnenie nových prometastatických funkcií nádorovoasociovanej karbonickej anhydrázy IX a jej interakcie so zápalovou odpoveďou
Program: APVV
Project leader: Mgr. Švastová Eliška PhD.
Annotation:Tumor microenvironment is a complex ecosystem consisting from components influencing each other - tumor cells, stromal cells, extracellular matrix and many soluble factors and cytokines. Characteristic feature of the tumor microenvironment-hypoxia is considered as indicator of bad prognosis. Among the most hypoxia-induced proteins is carbonic anhydrase IX (CA IX) whose increased expression in tissues is often correlated with high malignity and the main task of which is to maintain intracellular pH homeostasis linked with acidification of the extracellular space. It is known that many processes in cells are tightly controlled by the values of intracellular and extracellular pH. Such process is also the formation of invasive structures, so-called invadopodia, which represents an important step in tumor cells metastasizing. Intriguingly, CA IX protein can markedly affect their formation by its enzymatic activity. Our most recent results indicate that another mechanism by which CA IX could participate in the invasion process is its cross-talk with proteins such as Arp2/3, WASP and mDia, responsible for actin polymerization. The molecular mechanism of this interplay will be the subject of our research. Moreover, from the point of view of migration and invasion, the proteoglycan domain of CA IX has an interesting ability to bind ECM proteins, and hence promote dissemination of tumor cells. It was also proved that certain inflammatory mediators, such as COX-2 and IL-6, increase the expression of CA IX. Hypoxia, necrosis and inflammatory reaction are closely connected during malignant progression. Despite this fact it has not been elucidated yet how necrosis-related signaling modulates hypoxia at the molecular level. Therefore, by a detailed study of CA IX we would like to identify a functional link between necrosis-induced signaling molecules, hypoxia and invasive potential of tumor cells, and subsequently to search for possibilities of their influencing or inhibition.
Duration: 1.7.2015 - 30.6.2019

RECORD - DNA damage REsponse and preleukemic Clones in hematopoietic stem cells in diagnOstics, Risk estimation and treatment of peDiatric leukemia
Odpoveď na poškodenia DNA a preleukemické klony v hematopoetických kmeňových bunkách v diagnostike, v stanovení rizika a v liečbe detskej leukémie
Program: APVV
Project leader: doc. Ing. Beliaev Igor DrSc.
Annotation:A chromosomal translocation resulting in an in-frame preleukemic gene fusion (PGF) is often a primary genetic abnormality in the origination of acute childhood lymphoblastic/myeloid leukemia (ALL/AML). PGF arise in hematopoietic stem/progenitor cells (HSPC), often in utero. According to our results, which confirmed the data on UK and US newborns, about 1% of Slovak newborns harbor most frequent TEL-AML PGF in their umbilical cord blood (UCB). Our data have also suggested that only PGF arisen relatively early during embryonic/fetal development in specific HSPC population may facilitate overt leukemia. Using a bank of UCB cells, we will study FACS-sorted HSPC subpopulations from PGF positive UCB samples by PCR, DNA sequencing, and FISH. The obtained data may be used for early diagnostics of predisposition to ALL/AML and exclusion of UCB PGF positive samples from transplantation. DNA damage response (DDR) and apoptosis are crucial for origination and persistence of PGF and may be impaired in HSPC of subjects predisposed to leukemia. Ionizing radiation at high doses is known to induce leukemia. Exposure to electromagnetic fields (EMF) has also been related to increased risk of childhood leukemia. However, no data are available whether ionizing radiation at low doses and EMF, to which significant part of general public is exposed in modern society, are able to induce PGF in HSPC and whether PGF may be used for assessment of risks for ALL/AML. Induction of PGF, DDR and apoptosis will be studied in HSPC subpopulations using state-of-the-art techniques. Preleukemic HSPC are considered to be a cellular reservoir for relapses. We will study diagnostically relevant PGF in HSPC subpopulations from PGF positive ALL/AML patients at diagnoses, remission, and relapse and in their backtracked UCB. All data will be correlated with clinical outcome to the aim of validation this approach for minimal residual disease (MRD), adjustment of treatment, and prevention of relapses.
Duration: 1.7.2016 - 30.6.2019

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

Mechanisms of gold and magnetic nanoparticle effects on renal cells
Porovnanie mechanizmov účinku nanočastíc zlata a magnetitu na jednotlivé typy renálnych buniek
Program: VEGA
Project leader: Mgr. Bábelová Andrea PhD.
Annotation:Kidney is a unique organ characteristic by the high degree of heterogenity. Each cell type in the kidney has a distinct gene expression pattern and changes in the cellular composition largely impact on gene expression that is closely linked to the cell function. Different types of kidney cells have varying sensitivities to toxic substances that may accumulate in kidneys, including nanoparticles. Prolonged residency of nanoparticles in the kidney has been shown to induce toxicity with hallmarks similar to glomerulonephritis affecting all types of renal glomerular cells as mesangial cells, fibroblasts, or podocytes what may form a basis for reduced glomerular filtration capacityin nephrotic kidneys. Similarly, nanoparticle accumulation in the tubular basement membrane can be detrimental to tubular epithelial cells and so alter the ability of solute reabsorption by the kidney. Considering expansion of nanoparticles into biomedicine the type of renal toxicity studies are required to avoid potential health risks.
Duration: 1.1.2015 - 31.12.2018

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

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

PEEECS - Preparation of erythropoietin a therapeutic hormone affecting the production of red blood cells by expression in eukaryotic cell system and its further purification
Príprava erytropoetínu, terapeutického hormónu ovplyvňujúceho tvorbu červených krviniek, expresiou v eukaryotickom bunkovom systéme a jeho ďalšia purifikácia
Program: APVV
Project leader: Ing. Škultéty Ľudovít DrSc.
Duration: 1.7.2015 - 31.12.2018

Proteomic analyses of the interaction of host with pathogenic bacterium Coxiella burnetii
Proteomická analýza interakcie hostiteľa s patogénnou baktériou Coxiella burnetii
Program: VEGA
Project leader: Ing. Škultéty Ľudovít DrSc.
Duration: 1.1.2015 - 31.12.2018

REGENER - Axonal regeneration in biosynthetic nerve guide conduits.
Regenerácia nervových vlákien v biosyntetických vodičoch.
Program: APVV
Project leader: MVDr. Vanický Ivo CSc.
Annotation:In adult mammals, nerve fibers are capable of regeneration. In peripheral nerve after injury, axons from the proximal stump regrow across the site of injury into the distal stump and create new connections with their target organs. Current surgical techniques allow for a direct reconstruction of the severed nerve (end-to-end) only if the missing segment is not too large. After devastating injuries, autologous nerve grafts can be used. Synthetic nerve guides for nerve regeneration can be used as a substitute for autologous grafts. Regrowth of regenerating fibers across the synthetic nerve guides is limited to relatively short distances. This restriction is surprising, because in the distal stumps, regenerating axons are able to grow over long distances. Advances in the synthesis of biocompatible polymers provide new biomaterials with optimized properties. In the present project, we plan to use biosynthetic guides made from new elastomeric materials. The properties of the nerve guide will be modified and tested in vitro, with the goal to stimulate regeneration over long distances. The effectiveness of these modifications on regeneration process will be tested in vivo. 15 Žiadateľská organizácia Neurobiologický ústav SAV Co-ordinating organization Slovak Academy of Sciences, Institute of Neurobiology
Duration: 1.7.2015 - 30.6.2019

SWIREG - Regulation of the Swi5-Sfr1 complex by protein phosphorylation
Regulácia komplexu Swi5-Sfr1 pomocou fosforylácie
Program: APVV
Project leader: Ing. Čipáková Ingrid PhD.
Duration: 1.8.2018 - 30.6.2022

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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

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

Investigation of effect of acute and repeated asenapine (ASE) treatment on activity of neurons in extrastriatal brain, identification of activated neurons phenotype, and revealing whether chronic mild stress preconditioning may alter the effect of ASE
Skúmanie akútneho a chronického účinku azenapínu (AZE) na aktivitu neurónov v mimostriatálnych oblastiach mozgu, identifikovanie fenotypového charakteru aktivovaných neurónov a zistenie či účinok AZE je ovplyvniteľný chronickým predstresovaním zvierat.
Program: VEGA
Project leader: RNDr. Kiss Alexander DrSc.
Annotation:Antipsychotics (APs) are drugs used in the treatment of mental illnesses. The majority of morphological studies deals with the impact of APs in forebrain structures and only little is known about their effect in extrastriatal areas, whereas they act also extrastriatally and the extent of their action considerably differs one from another. Asenapine (ASE) is an atypical AP with low affinity to D2 and high affinity to serotoninergic (5-HT2A) receptors. We have described, as the first, the impact of ASE on the activity forebrain structures. This project will bring a new knowledge about acute and repeated effect of ASE in the extrastriatal areas, reveal the phenotype character of activated neurons, and disclose whether ASE impact may be modifiable by a stress preconditioning. The data obtained in this project might be perspectively helpful in the developing of new APs with reduced negative side effects and to lead to more integrated understanding of the neurobiology of serious mental illnesses.
Duration: 1.1.2016 - 31.12.2018

Effect of salivary gland extracts derived from different tick species on induction and biological activity of interferon-lambda 1.
Sledovanie vplyvu extraktov slinných žliaz (SGE) z rôznych druhov kliešťov na indukciu a na biologickú aktivitu IFN-lambda 1.
Program: VEGA
Project leader: Mgr. Bartíková Pavlína PhD.
Annotation:During bloodfeeding, tick salivary glands secrete into the damage area a broad spectrum of pharmacologically active substances interacting with host innate and adaptive immune systems. This manipulation of host defense reactions is important not only to successful ticks surviving also to facilitate transmission and replication pathogen into the host (SAT phenomenon). Interferons (IFNs), innate immune cytokines, contribute the first line of antiviral defence. Recently, IFNs lambda was found as new family of interferons, type III. Type III IFNs are structurally closed to interleukin 10(IL-10) and IL10–related cytokines, functionally are closely related to type I IFNs. Probably, IFN l1 could be important innate immunity activator, particularly at the site of viral infection, such as tick’s feeding site could be. Elucidation of the mode of action of tick bioactive molecules on the cell processes connected with interferons can provide new tools for understanding the mechanisms contribute on SAT phenomenon.
Duration: 1.1.2015 - 31.12.2018

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

Sulfide signaling as a potential mechanism in tumor´s treatment
Sulfidová signalizácia ako potenciálny mechanizmus pri liečbe nádorov
Program: APVV
Project leader: RNDr. Hudecová Soňa CSc.
Annotation:Hydogen sulfide, which was previously accounted as a toxic gas, is currently considered as a third gassotransmitter, playing a crucial role in a cell physiology and patophysiology. Changes in the metabolism of hydrogen sulfide lead to the development of pathophysiological states, e.g. hypertension, diabetes, inflammation, sepsis, neurodegenerative disases etc. This project is appointed to determine a role of the endogenous (formed by a cell) and also exogenous (added) H2S in selected types of cancer cells (pheochromocytomas, ovarial and kidney cells). We expect that by the H2S donors we will be able to modulate proliferation by these cells and also induction of the apoptosis (possibly through the calcium fluxes). Understanding the mechanism might contribute to development of new therapeutics based on the H2S release.
Duration: 1.7.2015 - 30.6.2019

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

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

The therapeutic effects of stem cells conditioned medium on the repair of the spinal cord damaged tissue: a comparative ex vivo study.
Terapeutické účinky kondiciovaného média kmeňových buniek na reparáciu poškodeného tkaniva miechy: porovnávacia ex vivo štúdia.
Program: VEGA
Project leader: RNDr. Slovinská Lucia PhD.
Annotation:Spinal cord injury is a neurodegenerative disease of the CNS, which leads to damage and death of the spinal cord cell population, namely neurons, oligodendrocytes, astrocytes. Cell therapy is a key area of regenerative medicine to find suitable sources of transplanted cells or their products, allowing restoration of damaged tissue. The aim of the present project is to establish an ex vivo model of traumatic injured CNS tissue in the form of organotypic spinal cord slices. Using this model we will investigate the effects of the conditioned medium of the stem cells (mesenchymal stem cells from bone marrow and adipose tissue, neural progenitors) on the repair of damaged rat spinal cord tissue. We compare the effectiveness of different conditioned media on the base of survival and proliferative potential of glial cell population, neurons and nerve fibers overgrowth. We suppose, that the ex vivo model of mechanical damage will be a good method for the study of potential therapeutic strategies in CNS damage.
Duration: 1.1.2016 - 31.12.2018

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 exosomes in the process of chemoresistence of ovarian carcinoma
Úloha exozómov pri vzniku rezistencie na chemoterapiu pri karcinóme ovária
Program: VEGA
Project leader: RNDr. Sedlák Ján DrSc.
Annotation:Ovarian cancer is the leading cause of women’s death for gynecologic malignancy in developed countries. The rapid development of the tumor and the impossibility of proper screening cause the disease diagnoses in the high stages in more than 75% of cases. The treatment consists of debulking surgery and chemotherapy. The disease, in most cases, despite chemosensitive primary tumor, relapses in average 18 months after the treatment with progressive development of chemoresistance. 5-year survival rate is 25-35 %. It is therefore necessary to identify new prognostic and predictive biomarkers that would allow earlier diagnosis of the disease and reveal resistance to chemotherapy. Exosomes, small 30-100 nm big vesicles, are involved in physiological and pathological processes, e.g. tumor growth, the development of metastases, immune system stimulation and intercellular transfer of miRNA. Exosomes in the peripheral blood, its miRNA composition, present a potential biomarker for better diagnosis of ovarian cancer.
Duration: 1.1.2016 - 31.12.2018

The role of hypoxia-induced carbonic anhydrase IX in invasion processes of tumor cells.
Úloha hypoxiou-indukovanej karbonickej anhydrázy IX v invazivite nádorových buniek
Program: VEGA
Project leader: Mgr. Švastová Eliška PhD.
Annotation:Carbonic anhydrase IX (CA IX) is hypoxia inducible protein whose expression is associated with tumors with bad prognosis. Hence, these cells have a high invasive potential. Formation of invasive structures, i.e. invadopodia is an essential step in tumor cell penetration into ECM. This process is strictly controlled by intracellular and extracellular pH. By its enzymatic activity CA IX acidifies pHe and, at the same time, neutralizes pHi, which could significantly influence invadopodia formation. Our microarray data indicate that CA IX level also affects the expression of proteins, such as Arp2/3 or WASP which form a signaling complex important for actin polymerization in invadopodia. Besides its pH regulatory function CA IX could have an impact on the formation of signalozome regulating the growth of these invasive structures, Moreover, proteoglycan domain of CA IX could facilitate intravasation and extravasation and in such way support tumor cells dissemination by its ability to bind ECM proteins.
Duration: 1.1.2015 - 31.12.2018

Adipostem - Role of IL-6/NF-κB /HIF-1 axis in adipose tissue mesenchymal stromal cells-mediated breast cancer cells stemness
Úloha IL-6/NF-κB/HIF-1 signálnej dráhy v kmeňovosti prsníkových nádorových buniek sprostredkovanej mezenchýmovými stromálnymi bunkami izolovanými z tukového tkaniva
Program: APVV
Project leader: Mgr. Kučerová Lucia DrSc.
Annotation:Adipose tissue mesenchymal stromal cells (AT-MSC) are an important component of breast cancer microenvironment and though secretion of different molecules are able to influence many features of tumor cells. Our previous results have shown increased dediferentiation and chemoresistance (stem cell-like properties) of breast cancer cells (BCC) after cultivation with ATMSC or their secreted factors. We propose, that AT-MSC-secreted IL-6 activates NF-κB/HIF-1 axis, which is responsible for maintenance of stemness properties of tumor cells. We will analyze cell cycle progression/quiescence, mammosphere formation and expression of pluripotency markers in breast cancer cells cultivated in the presence of AT-MSC and/or their secreted factors. Also, to confirm existence of NF-κB/HIF-1 axis and its role in stemness of BCC, we will determine HIF-1 activation and localization in NF-κB and/or HIF-1–suppressed BCC.
Duration: 1.1.2017 - 31.12.2018

The role of carbonic anhydrase IX in tumor metabolism: regulation, function and clinical significance
Úloha karbonickej anhydrázy IX v nádorovom metabolizme: regulácia, funkcia a klinický význam
Program: VEGA
Project leader: RNDr. Gibadulinová Adriana CSc.
Annotation:Tumor cells are capable to adapt their metabolism to the tumor tissue microenvironment stress, as is lack of oxygen and nutrients. They become less dependent on oxidative phosphorylation and use glycolysis to receive not only the energy required for survival, but also the biomass needed for proliferation. Such tumor metabolism promote an aggressive phenotype and progression of cancer. Based on our preliminary proteomic data, in this project we will stydy the role of hypoxia - induced carbonic anhydrase IX ( CA IX ) in tumor metabolism and its cooperation with the metabolic pathways and signaling. In addition to the experimental 2D and 3D cell models, the results will be validated on clinical tissue samples and sera from patients with breast tumors . In the project we will use the latest methods of molecular and cell biology ( including cultivation cells in hypoxia and measurements of cell parameters in real time), immunodetection methods as well as unique reagents available in our laboratory.
Duration: 1.1.2015 - 31.12.2018

The role of the nervous system in etiopathogenesis of experimental melanoma
Úloha nervového systému v etiopatogenéze experimentálneho melanómu
Program: VEGA
Project leader: Ing. Tillinger Andrej PhD.
Annotation:Malignant melanoma represents a serious tumor disease. The incidence and mortality caused by this disease annually significantly increases. Explanation of the mechanisms associated with the development and progression of malignant melanoma requires research not only on the level of malignant cells transformation, but also on the level of processes running in its micro and macro environment, this includes also components of the nervous system. Several experimental and clinical studies have shown involvement of the nervous system in the etiopathogenesis of cancer. It is proved that nervous system may affect tumor proliferation and metastasis formation via modulation of cellular immune reactions, regulation of neuroendocrine stress reaction, as well as via other pathways including parasympathetic and sensitive nerves. The aim of the proposed project is to examine the role of the nervous system in etiopathogenesis of experimental melanoma using various experimental approaches.
Duration: 1.1.2016 - 31.12.2018

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 polysulfides in regulation of chloride channels and respiration of mitochondria
Úloha polysulfidov v regulácii chloridových kanálov a dýchania mitochondrií
Program: VEGA
Project leader: Mgr. Grman Marián PhD.
Annotation:Endogenously produced hydrogen sulfide (H2S) influences many physiological functions. Molecular mechanism of H2S mediated protein modification – persulfidation and a role of polysulfides in this mechanism are not fully understood yet. Mitochondria as the energetic centre of the cell is the main site of H2S oxidation, that leads to polysulfide generation. The main aim of this project is to study the effect of polysulfides effect on activity of mitochondrial chloride channels, which are involved in mitochondrial transmembrane potential regulation, mainly under oxidative stress conditions. For this purpose we will use method of incorporation of ion channels into bilayer lipid membrane. We will also investigate effect of polysulfides on respiration and oxidative phoshorylation of mitochondria using the oxygen electrode. These results could contribute to better understanding of the role of polysulfides in mitochondrial redox regulation and their possible involvement in pathological states formation.
Duration: 1.1.2016 - 31.12.2018

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.
Duration: 1.1.2018 - 31.12.2021

TEaMSTeR - Role of Stress Response Induced in Mesenchymal Stromal Cells in Extrinsic Drug Resistance of Human Tumor Cells
Úloha stresovej odpovede mezenchýmových stromálnych buniek v rezistencii ľudských nádorových buniek na liečbu
Program: VEGA
Project leader: RNDr. Matúšková Miroslava PhD.
Annotation:Cells of the tumor microenvironment are recognized as major determinants of the tumor biology. The adjacent non-malignant cells regulate drug responses of the cancer cells by the secreted paracrine factors and interactions. Human mesenchymal stromal cells (MSC) actively contribute to many aspects of tumor biology including extrinsic effects on the drug responses in tumors. MSC were proven to exhibit increased drug resistance. The idea of the project is to examine the intracellular signaling pathways activated upon cytotoxic stimulus in human MSC because these were not described in detail. Moreover the stress response activated upon drug exposure may activate the cellular program preventing damage and promoting the tissue regeneration, and thus contribute to altered drug responses. We intend to evaluate the MSC-exerted effect on the drug responses in tumor cells, verify these effect on animal models and identify options for therapeutic augmentation based on the tumor microenvironment targeting.
Duration: 1.1.2015 - 31.12.2018

Role of calcium signaing mediated by IP3 receptors in cancer cells derived from clear-cell carcinoma
Úloha vápnikovej signalizácie cez IP3 receptory v nádorových bunkách svetlobunkových karcinómov.
Program: VEGA
Project leader: prof. Ing. Križanová Oľga DrSc.
Duration: 1.1.2016 - 31.12.2018

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

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 LCMV infection on the activity of HIF-regulated signal transduction pathways
Vplyv infekcie vírusu lymfocytovej choriomeningitídy na aktivitu signálnych dráh regulovaných transkripčným faktorom HIF-1
Program: VEGA
Project leader: Ing. Tomášková Jana PhD.
Annotation:The outcome of viral infections can be significantly affected by the components of tissue physiology and cellular microenvironment. Low oxygen tension exerts significant effect on the replication of several DNA and RNA viruses in cultured cells. Recently, we have demonstrated that chronic hypoxia enhances lymphocytic choriomeningitis virus (LCMV) replication in hypoxia inducible factor (HIF) -dependent manner, but molecular mechanisms underlying this process are not yet known. Therefore, the main goal of the proposed project is to reveal the biological impact of LCMV infection on the activity of HIF-1-regulated signal transduction pathways in cells cultured under low or atmospheric oxygen tensions. We will examine whether LCMV affects HIF-1α levels by modulating its transcription, translation, or stabilization. Identification of involved components and/or mechanisms will contribute to a more detailed understanding of viral pathogenesis, may reveal new aspects of host regulation and offer potential therapeutic targets.
Duration: 1.1.2015 - 31.12.2018

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

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 -

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

NEXTVIR - Usage of next-generation sequencing for virome analysis of medically and economically relevant organisms.
Využitie sekvenovania novej generácie pre analýzu virómu medicínsky a hospodársky významných organizmov.
Program: APVV
Project leader: RNDr. Klempa Boris DrSc.
Duration: 1.7.2016 - 30.6.2019

APTADIAG - Development of novel diagnostic method for clinical oncology based on the interaction of DNA aptamers with proteins
Vývoj progresívnej diagnostickej metódy pre klinickú onkológiu založenej na interakcii DNA aptamerov s proteínmi
Program: APVV
Project leader: RNDr. Bízik Jozef DrSc.
Annotation:The project is focused on the development of novel diagnostic method for clinical oncology based on the interaction of DNA aptamers with membrane proteins. For this purpose the extensive basic research will be performed with focus on the study of the mechanisms of interaction DNA aptamers with model proteins incorporated into the supported lipid membranes as well as with tumor markers at the surface of the cell cultures. The progressive biophysical methods will be applied such as acoustic thickness shear mode method, atomic force misroscopy, single molecule force spectroscopy, fluorescence resonance energy transfer and others. The exprienced teams composed of senior scientists, young researchers and PhD students from Faculty of Mathematics, Physics and Informatics of Comenius University in Bratislava and from two Research Institutes of the Slovak Academy of Sciences – Institute of Animal Biochemistry and Genetics and Cancer Research Institute will be involved in the project. We assume that will obtain new knowledge on the mechanisms of interaction of DNA aptamers with membrane proteins depending on the lipid composition as well as with tumor markers at the surface of cell cultures depending on the type of the tumor and the progress of dissease.
Duration: 1.7.2015 - 30.6.2019

Development of Rickettsia antibodies detection system using an enzyme immunological assay
Vývoj systému na detekciu rickettsiálnych protilátok s využitím enzýmovej imunoanalýzy
Program: VEGA
Project leader: Mgr. Quevedo Diaz Marco PhD.
Annotation:Rickettsiae are obligate intracellular bacteria that proliferate within the cytoplasm of eukaryotic cells. In humans, members of the genus Rickettsia can cause diverse human diseases such as epidemic typhus, Mediterranean spotted fever and Tibola, this last one caused by Rickettsia slovaca, one of the most distributed rickettsia in our region. One of the biggest challenges for physicians is diagnose these infections early in their clinical course, when antibiotic therapy is most effective but sometimes they are undiagnosed or misdiagnosed and lead to fatal cases. Although rickettsiae can be isolated from or detected in clinical specimens, serological tests still remain an indispensable tool in the diagnosis of rickettsial diseases. The goal of this proposal is identify specific rickettsial immunogenic proteins (markers) from SFG by proteomics techniques, screening of rickettsial membrane components, generate recombinant proteins and employ them to improve detection in diagnosis of rickettsial infections.
Duration: 1.1.2016 - 31.12.2018

Importance of the Na/Ca exchanger in ovarian tumor cells, its modulation and a role in inducing apoptosis.
Význam Na/Ca výmenníka v ovariálnych nádorových bunkách, jeho modulácia a úloha pri vyvolaní apoptózy.
Program: VEGA
Project leader: Mgr. Lenčešová Ľubomíra PhD.
Annotation:Tumor cells have altered signaling pathways for calcium. These changes depend on many factors, e.g. type of tumor, origin of tumor cells, etc. Alteration in calcium signaling is caused by modification in a function of calcium transporters that are localized on the plasma membrane, but also on an intracellular organelles. One of them, which might significantly contribute to the flow of calcium ions in the tumors, is Na+/Ca2+ exchanger (NCX). NCX can transport calcium into the cell and also out of the cell depending on the state and the condition of the cell. We assume that in tumor cells NCX operates in the reverse mode, therefore NCX transports calcium into the cell and thus affects others intracellular calcium transporters. The project will study the role of NCX in ovarian cancer cells. We will focus on studying the mechanism of operation of NCX, potential partners from among the receptor proteins and the induction of apoptosis in the modulation of NCX function under normal conditions and during hypoxia.
Duration: 1.1.2016 - 31.12.2018

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: 149