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Biomedical Research Center SAS

International projects

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

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

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 - 31.12.2020

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

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 - 31.7.2020

AIM - Aedes Invasive Mosquitoes
Invázne druhy komárov z rodu Aedes
Program: COST
Project leader: RNDr. Čabanová Viktória PhD.
Annotation:V roku 2012 bol na Slovensku po prvýkrát zachytený invázny druh komára Aedes albopictus. Odvtedy sa jeho opakovaný výskyt u nás nepotvrdil. V okolitých krajinách Slovenska je však potvrdený výskyt a rozširovanie viacerých inváznych druhov komárov ako Aedes albopictus, Aedes japonicus alebo Aedes koreicus a preto je vysoký predpoklad, že tieto druhy budú ďalej introdukované aj na naše územie. Monitoring inváznych druhov komárov z rodu Aedes na novom, neosídlenom území je však pomerne náročný, pretože sa na začiatku vyskytujú len v malých ohraničených ohniskách v mieste ich introdukcie. Preto je pre zachytenie inváznych druhov v prvotnej fáze ich prieniku kľúčové vybrať správnu monitorovaciu techniku a najmä územie s vysokým rizikom introdukcie. Pod takéto územia spadajú na Slovensku najmä letiská a diaľničné komunikácie spájajúce nás s krajinami, kde sa výskyt týchto druhov stáva bežným, napr. Taliansko. Cieľom nášho projektu je monitorovanie vysoko rizikových oblastí pre introdukciu inváznych druhov komárov na základe protokolu vytvoreného konzorciom a zdieľanie týchto výsledkov pre vytvorenie celoeurópskych rizikových modelov.
Duration: 29.1.2020 - 5.9.2022

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

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

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

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

Novel strategies aimed to improve the physical fitness, clinical symptoms and quality of life in the early-stage Parkinson’s disease patients: Regular exercise training and carnosine
Nové stratégie ako zlepšiť fyzickú zdatnosť, klinické symptómy a kvalitu života pacientov vo včasných štádiách Parkinosonovej choroby: Pravidelné cvičenie a karnozín
Program: Bilaterálne - iné
Project leader: doc. MUDr. Ukropcová Barbara PhD.
Annotation:Aging-associated decline in brain & metabolic functions can be substantially accelerated by sedentary lifestyle. Even an older adult brain can adapt to physiological stimuli, which brings a strong incentive for implementing regular exercise in prevention and treatment of neurodegenerative diseases. Contracting skeletal muscle is the source of many bioactive molecules, coordinating adaptive response to exercise across the body. Dipeptide carnosine, a safe dietary supplement with antioxidant, antiAGEs, antiinflammatory, antidiabetic and neuroprotective properties, has a potential to enhance benefits of regular exercise. We therefore aim to define exercise and/or carnosine-induced effects (i) on behavioral, neurophysiological (ERPs & fMRI) and motor functions, (ii) on the whole-body (clamp) & muscle metabolism (31P-MRS), (iii) on muscle carnosine content (1H-MRS) as well as (iv) on muscle adaptive response to exercise (muscle biomarkers) and (v) exercise-regulated serum and cerebrospinal fluid biomarkers in patients with early-stage Parkinson`s disease. Next, we plan to explore expression and secretion of specific exercise and/or carnosine regulated bioactive molecules in vitro using human primary skeletal muscle cells. This complex approach will allow us to explore the putative synergistic effects of exercise and carnosine, with a potential to identify novel early diagnostic, preventive or therapeutic strategies and bring direct health benefits to Parkinson‘s disease patients.
Duration: 1.1.2019 - 31.12.2021

UNMET - UNveiling the MEchanism(s) underlying the switch to mania during antidepressant treatment: The role of glutamate
Odkrytie mechanizmov zodpovedných prešmyk z depresie do mánie počas antidepresívnej liečby: úloha glutamátu
Program: ERANET
Project leader: prof. PharmDr. Ježová Daniela DrSc.
Duration: 1.7.2019 - 30.6.2022

RyRinHeart - RyRinHeart - Discovery of Ryanodine Receptor Inhibitors for Heart Diseases
RyRinHeart - Vývoj inhibítorov ryanodínového receptora pre srdcové ochorenia
Program: Bilaterálne - iné
Project leader: Ing. Zahradníková Alexandra DrSc.
Annotation:Cardiac ryanodine receptors (RyR2) control the pumping function of the heart by regulating calcium release required for cardiac myocyte contraction. Many heart diseases are accompanied by disorders of calcium release. These disorders could be suppressed by drugs that prevent unwanted RyR2 activity. The aim of this project is to develop specific inhibitors, adapted to the structure of cardiac RyR2, with the potential to treat calcium handling disorders in heart disease. We will use our original knowledge of the structure of RyR2 to identify loci in the 3D-structure of RyR2 that reduce its activity by ligand binding. This will allow us to design and synthesize RyR2 inhibitors. We will test their efficacy in experiments monitoring RyR activity. The in situ efficacy of selected agents, most promising for regulation of RyR2 function, will be tested on isolated cardiac myocytes and finally on the hearts of healthy animals and animals with heart disease. Methodologically, the project is based on two pillars: molecular structure simulations, molecular dynamics, and computer-assisted drug design, the main body of expertise being the Turkish side, and a wide range of experimental and theoretical methods of studying ion channel function and calcium signalling (biochemical and electrophysiological methods, confocal microscopy, mathematical modelling of dynamics of intracellular processes), where expertise will be provided by the Slovak side. The project aims to contribute to the solution of a serious medical problem using advanced technologies, original expertise and new approaches developed in collaborating laboratories.
Duration: 1.1.2020 - 31.12.2022

COST-ENBA - Drosophila salivary gland secretory proteins as tunable and biodegradable natural glue
Sekretorické proteíny slinných žliaz Drosophila ako biodegradovateľné prírodné lepidlo s programovateľnými vlastnosťami
Program: COST
Project leader: RNDr. Farkaš Robert CSc.
Duration: 1.1.2017 - 31.12.2020

VISION - Strategies to strengthen scientific excellence and innovation capacity for early diagnosis of gastrointestinal cancer
Stratégia ako posilniť excelentnosť a inovačnú kapacitu na včastnú diagnostiku rakoviny gastrointestinálneho traktu
Program: Horizont 2020
Project leader: RNDr. Gábelová Alena CSc.
Annotation:The main objective of VISION is to strengthen excellence and innovation capacity of the Biomedical Research Center of the Slovak Academy of Sciences (BMC SAV). Close cooperation with four European leading research institutions will enhance the credibility, competitiveness, and recognition of BMC SAV, contribute to overcome existing gaps in oncology research and reinforce the capacity for early diagnostics and innovative treatment approaches. Beyond increased scientific performance, the collaborative approach may help to identify factors contributing to an extremely high incidence of colon and pancreatic cancer in Slovakia.
Project web page:http://vision.savba.sk
Duration: 1.10.2019 - 30.9.2022

The role of specific cell-types of the median raphe in behavior: the excitatory vesicular glutamate transporter 3 and the inhibitory GABA
Úloha špecifických typov buniek v median raphe v správaní: excitačný vezikulárny glutamátový transportér 3 a inhibičná GABA
Program: Bilaterálne - iné
Project leader: prof. PharmDr. Ježová Daniela DrSc.
Annotation:This project aimed to enlarge the understanding of the role of specific cell-types of median raphe in depressive-like and social behavior and learning, thus leading to a deeper insight into several neuropathological states (major depression, social cognition deficit in autism spectrum disorder, Alzheimer’s related memory impairment). Glutamate and GABA are in the center of interest of psychoneurobiological research as the main excitatory and inhibitory neurotransmitters, respectively, which are widely distributed through the brain and proved to be involved in many physiological as well as pathological processes. Glutamate producing neurons can be characterized by the presence of vesicular glutamate transporter (VGluT) with three different isoforms. The VGluT3 was described and cloned in 2002, thus, our knowledge of its role is still limited. GABAergic cells can be visualized by the presence of vesicular GABA transporter (VGAT). Previously, including our common studies, pharmacological modulation of glutamate receptors was the most frequently used experimental approach. Later, the availability of knockout mice strains deepened our knowledge. Nowadays mice lines containing the Cre recombinase enzymes in specific cell-types are generated making selective manipulation of different cell-types on specific brain areas possible. Combining them with opto- and pharmacogenetic techniques, the research approaches new dimensions making a detailed understanding of the role of glutamatergic and GABAergic cells of small brain areas such as median raphe possible.
Duration: 1.1.2019 - 31.12.2021

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

NExT - Establishing an algorithm for the early diagnosis and follow-up of patients with pancreatic neuroendocrine tumors
Zavedenie algoritmu na včasnú diagnostiku a sledovanie pacientov s pankreatickými neuroendokrinnými nádormi
Program: ERANET
Project leader: Mgr. Smolková Božena PhD.
Annotation:Background and rationale: Standardized clinical management of pancreatic neuroendocrine tumours (PNETs) is limited by different aspects of the disease, as its relative rarity (1 per 100,000 individuals), heterogeneous clinical presentation (hormonally functional or non-functional), the limited understanding of tumour biology and behaviour and the lack of prospectively evaluated risk stratification systems. While surgical excision remains the primary therapy, as early detection is uncommon, most patients present with metastatic disease at diagnosis and a reduced life expectancy as they are not candidates for resection. Hypothesis: Prompt, specific and sensitive detection and characterisation of PNETs could lead to early detection, increasing the chance for surgical intervention and improve patients’ survival. Circulating tumour cells (CTCs) shed from primary tumours are considered attractive biomarkers for liquid biopsy as they represent an early step in blood-borne metastasis. Several studies propose that during malignant progression cancer cells undergo an epithelial-to-mesenchymal transition (EMT), acquire invasive properties and stem cell-like features. Aims: The present proposal, by building up a tissue bank of genetically characterized tumours, development of patient-derived rare tumour xenografts (PDXs) and organoids, aim to identify PNET-specific biomarkers urgently needed to design a next generation nanotechnology based microfluidic device and integrate the technology of minimally invasive liquid biopsy in the early detection of PNETs. Methods: Serum and tissue samples (fresh and FFPE) will be collected from PNET patients and their clinical and lab records will be recorded. An expression study and genomic analysis will be performed in clinical samples by different molecular techniques whereas in parallel organoids, PDX and CDX will be established. A next generation nanotechnology based microfluidic device will be developed, based on the acquired data. Expected results and potential impact: Better understanding of the etiopathogenetic determinants involved in PNETs formation resulting from the multidisciplinary collaboration within ‘NExT” consortium will hopefully deliver a nanotechnology-based microfluidic (next generation) device that by means of CTCs detection will present a powerful tool for the early detection of PNET tumours and follow-up of patients, contributing to their better medical treatment.
Duration: 1.9.2019 - 31.8.2022


National projects

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

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

Expression analysis of miRNA genes regulating the biology of cancer stem cells in breast cancer patients
Analýza expresie génov pre miRNA regulujúcich biológiu nádorových kmeňových buniek u pacientok s karcinómom prsníka
Program: VEGA
Project leader: Mgr. Kalinková Lenka 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

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

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

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

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

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

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

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

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

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

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

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

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

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

GlycoPro - Glycoprofiling of proteins present in serum and exosomes for early prostate cancer diagnostics
Glykoprofilácia proteínov prítomných v sére a v exozómoch pre včasnú diagnostiku rakoviny prostaty
Program: Iné projekty
Project leader: RNDr. Gábelová Alena CSc.
Annotation:In this project we would like to identify novel glycan-based prostate cancer (PCa) biomarkers based on specific glycoprofiling of selected proteins either present in serum or in exosomes. We will integrate various assay protocols for such glycoprofiling using lectin-based ELISA, magnetic ELISA, antibody-lectin microarrays, electrochemistry, Surface Plasmon Resonance (SPR) and LFA (Lateral Flow Assays, pregnancy-like tests). The innovation of the project proposal can be summarized as follows: • Specific glycoprofiling of zinc -glycoprotein (ZAG) and prostatic acid phosphatase (PAP) present in the serum as potential PCa biomarkers; • Use of exosomes as a rich source of five glycoproteins to be glycoprofiled by lectins; • Application of innovative assay strategies with various assay formats; glycoproteins/exosomes will be affinity enriched by magnetic beads and the whole complex without any glycoprotein/exosome released will be incubated with lectin modified interface; • Use of LFA for glycoprofiling of proteins, which has not been used in the analysis of real samples.
Duration: 1.12.2019 - 30.11.2021

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

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

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

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

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

ImmunoGEN - Implementation of modern genomic analyzes to improve clinical diagnostic and therapeutic procedures of Immune Disorders
Implementácia moderných genomických analýz na zlepšenie klinických diagnostických a terapeutických postupov imunitných porúch
Program: Iné projekty
Project leader: prof. RNDr. Kádaši Ľudevít DrSc.
Annotation:The project is focused on testing the applicability of advanced technologies using massive parallel sequencing to clinical practice to improve patient care with selected immune disorders. The aim of the project is to optimize and implement molecular-diagnostic methods at the level of exome and whole genome sequencing in patients with primary immunodeficiency and patients with inflammatory bowel diseases to improve diagnostic characterization, pharmacogenomic predictions, disease / treatment monitoring and prediction of the risk of developing disease complications with subsequent setting of the effective therapeutic algorithm. The diagnostic benefit dimension of the proposed methodology extends to the potential use in prediction-preventive applications, not only in the scope of tested model immune diseases, but also in other genetically determined diseases with existence of a possible more effective preventive program such as cardiovascular and oncological diseases.
Duration: 1.12.2018 - 31.12.2020

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

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

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

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

Is 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

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

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

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

CAScADE - Markers overlapping chemoresistance and metastatic potential in colorectal cancer - alhedyde dehydrogenase and its clinical relevance
Markery prekrývajúce chemorezistenciu a metastázovanie kolorektálneho karcinómu - úloha aldehyddehydrogenázy a jej klinická relevancia
Program: Iné projekty
Project leader: RNDr. Matúšková Miroslava PhD.
Annotation:Metastases occur in more than half of the patients suffering from colorectal cancer (CRC). Their prognosis is unfavourable. Acquired chemoresistance is significant obstacle in treatment of patients with metastases. There is an increasing number of evidence that there is a functional overlap between chemoresistance and metastatic dissemination. The mechanisms of this phenomenon are not fully understood in CRC. We demonstrated significantly increased activity of aldehyde dehydrogenases (ALDH), particularly the 1A3 isoform on chemoresistant-spontaneously metastatic cell line. Transient molecular silencing of ALDH1A3 led to partial response to chemotherapy. We aim to verify a hypothesis that ALDH1A3 or other ALDH1 isoforms are common marker for chemoresistance and invasive phenotype in CRC, and knockout of ALDH1, or inhibition of associated signalling pathways, decreases the aggressive phenotype. The clinical relevance we confirm on organoids and patient-derived xenografts as well as by retrospective analysis of clinical material archived in biobank of National Cancer Institute.
Duration: 1.11.2019 - 31.12.2021

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

Mechanisms of skeletal muscle adaptation to regular exercise in patients with chronic metabolic and inflammatory disease
Mechanizmy adaptácie kostrového svalu pacientov s chronickým metabolickým a zápalovým ochorením na pravidelné cvičenie
Program: VEGA
Project leader: RNDr. Novotová Marta CSc.
Annotation:Low physical fitness is associated with impaired muscle functional parameters and high risk of chronic metabolic disease. In patients with idiopathic inflammatory myopathy, skeletal muscle function deteriorates also because of systemic inflammatory process, but it often persists even after suppression of inflammation. Regular exercise positively affects energy metabolism and muscle functional state in healthy individuals as well as in patients with metabolic disease or myopathy. Aim of this project is to identify structural, functional and molecular determinants of beneficial effects of exercise on mitochondrial respiration, metabolic substrate preference, myocyte ultrastructure and contractile function. Skeletal muscle biopsy & differentiated muscle cells obtained from metabolically well-characterized patients before/after the exercise intervention will be used. This knowledge is a key to our efforts to tackle the basic pathophysiological determinants of idiopathic inflammatory myopathy.
Duration: 1.1.2019 - 31.12.2021

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

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

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

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

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

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

MolBioSem - Molecular biomarkers of relapse in seminoma clinical stage I patients
Molekulárne biomarkery relapsu pri seminómoch klinického štádia I
Program: Iné projekty
Project leader: Mgr. Chovanec Miroslav PhD.
Annotation:Clinical stage I seminoma (S-CS I) patients have a very good prognosis, reaching 98% survival. However, a small proportion of these patients relapse and the prognosis of these patients is significantly worse. There are currently no reliable biomarkers that stratify S-CS I patients, although primary tumor size ≥ 4 cm and rete testis invasion (RTI) are considered to be negative prognostic factors. The present project aims to identify molecular biomarkers that timely and accurately stratify S-CS I patients according to the risk of relapse. We intend to find molecular biomarkers of RTI, whose expression significantly associates with the risk of relapse in S-CS I patients. The factors of poor prognosis in S-CS I will further be sought within DNA repair processes, where the levels of DNA repair proteins will be correlated with the level of their regulation through epigenetic mechanisms and hypoxia. We will also examine proliferative activity as well as lymphocyte infiltrate in S-CS I patients. To achieve these goals, a comprehensive interdisciplinary approach using a wide range of methods and biological material will be used.
Duration: 1.10.2019 - 21.12.2021

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

Molecular-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

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

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

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

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

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

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

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

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

SGT - Of Sheep, Goats and Tick-borne Encephalitis virus
O ovciach, kozách a víruse kliešťovej encefalitídy
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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

HYPOMITGEN - -
Štúdium genetických príčin zriedkavých ochorení s dôrazom na metabolické poruchy asociované s hypoglykémiami a poruchy mitochondrií
Program: APVV
Project leader: RNDr. Gašperíková Daniela DrSc.
Duration: 1.8.2018 - 31.7.2022

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

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

Study of pro-metastatic functions of carbonic anhydrase IX, relationship between CA IX and mucins and hypoxic microenvironment in pancreatic cancer.
Štúdium prometastatických funkcií karbonickej anhydrázy IX, jej vzťahu k mucínom a hypoxického mikroprostredia v rakovine pankreasu.
Program: VEGA
Project leader: Mgr. Švastová Eliška PhD.
Annotation:Pancreatic cancer especially intraductal papillary mucinous neoplasms (IPMNs) are characterized by aberrant expression of different types of mucins. Although the overall prognosis for patients with IPMNs is better than it is for pancreatic ductal adenocarcinoma (PDAC) a subset of patients develops invasive tumors. Carbonic anhydrase IX is hypoxia induced protein whose expression, in many cancers, is associated with higher metastatic potential and poor prognosis of patients, also in cohort of patients with pancreatic ductal adenocarcinoma with lower survival. Genevestigator analysis revealed co-expression of CA9 with mucins (e.g. MUC1, MUC5AC) in IPMNs that progress from adenoma to carcinoma. Characterization of CA IX - mucins relationship and their role in epithelial-mesenchymal transition in pancreatic cancer and the impact of CA IX-related tumor microenvironment on pancreatic cancer progression is essential for adequate therapeutic strategies to overcome this lethal disease.
Project web page:https://www.minedu.sk/data/att/13859.pdf
Duration: 1.1.2019 - 31.12.2022

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

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

The 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

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

The role of glutamate transporters in blood cells in ischemic tolerance
Úloha glutamátových transportérov krvných buniek v ischemickej tolerancii
Program: VEGA
Project leader: RNDr. Bonová Petra PhD.
Annotation:The role of glutamate changed dramatically in ischemic conditions. The neurotoxic effect of glutamate (excitotoxicity) is one of the most important parameters determining the final extent of damaged tissue. Glutamate transporters (EAATs) localized on the membranes of neurons and glia are responsible for its scavenging from extracellular space. Their activity is significantly influenced by the ischemic condition. Same transporters were described as a part of blood cell membranes. Because blood cells are responsible for improved resistance of sensitive neuronal tissue to ischemia after appropriate stimulation, the main focus of the presented project is to identify the role of blood cells glutamate transporters in ischemic tolerance.
Duration: 1.1.2018 - 31.12.2020

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

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

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

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

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

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

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

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

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

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 - 30.6.2021

CEMEA - -
Vybudovanie Centra pre využitie pokročilých materiálov Slovenskej akadémie vied
Program: Štrukturálne fondy EÚ Výskum a inovácie
Project leader: Mgr. Švastová Eliška PhD.
Duration: 1.11.2017 - 30.6.2023

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

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

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

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

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

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

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

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

PhenoTOOL - Development of novel diagnostic and predictive high-dimensional immunophenotyping tool for hematological malignancies
Vývoj nového diagnostického a prediktívneho vysokodimenzionálneho imunofenotypizačného nástroja pre hematologické malignity
Program: Iné projekty
Project leader: RNDr. Jakubíková Jana PhD.
Duration: 1.11.2019 - 31.12.2021

Projects total: 126