Project
Biomedical Research Center SAS
International Projects
A4L_ACTIONS - Alliance for Life Sciences: From Strategies to Actions in Central and Eastern Europe
Aliancia pre živé vedy: od stratégií k činom v strednej a východnej Európe
| Duration: | 1. 5. 2021 - 30. 4. 2024 |
| Evidence number: | SC1-HCO-03-2020-964997 |
| Program: | Horizont 2020 |
| Project leader: | prof. RNDr. Pastoreková Silvia DrSc. |
| Annotation: | Research and innovation (R&I) plays a pivotal role in addressing Europe’s societal challenges including ensuring health and wellbeing of the citizens. Differences still persist in R&I performance between countries despite significant investments. In the health sector, the R&I gap can profoundly affect the quality of health and life of European citizens. Continuing the success of Alliance4Life, the EU-funded A4L_ACTIONS project aims to tackle the health R&I gap by improving the culture, governance, recognition and innovation potential of the health research-performing institutions in the lower-performing Central and Eastern European countries. This will help increase their attractiveness and pave the way for collaborations with advanced European countries. |
| Project web page: | https://alliance4life.ceitec.cz |
DE-PASS - DE-PASS Determinants of Physical Activities in Settings
DE-PASS Determinanty pohybovej aktivity v modernej spoločnosti
| Duration: | 22. 7. 2020 - 21. 4. 2024 |
| Evidence number: | COST CA19101 |
| Program: | COST |
| Project leader: | prof. MUDr. Ukropcová Barbara PhD. |
NETSKINMODELS - European Network for Skin Engineering and Modeling
Európska sieť pre kožné inžinierstvo a modelovanie
| Duration: | 15. 9. 2022 - 14. 9. 2026 |
| Evidence number: | CA21108 |
| Program: | COST |
| Project leader: | RNDr. Šramková Monika PhD. |
| Project web page: | https://www.cost.eu/actions/CA21108/ |
ERA4HEALTH - European partnership fostering a European Research Area (ERA) for health research
Európske partnerstvo prehlbujúce spoluprácu v rámci Európskeho výskumného priestoru (ERA) pre zdravotnícky výskumu
| Duration: | 1. 11. 2022 - 30. 10. 2029 |
| Evidence number: | 101095426 |
| Program: | Horizont Európa |
| Project leader: | doc. MUDr. Imrich Richard DrSc. |
| Annotation: | Excellent EU programs push health R&I but are not sufficient. Synergy with strategic initiatives in MS and a new model for impactful collaborations are needed to address the challenges for health. ERA4Health brings the opportunity to increase EU transnational collaborative research funding by creating a funding body for joint programming in priority areas addressing EU Public Health Needs, with total duration of 7 years. ERA4Health focuses on tackling diseases and reducing disease burden and the following challenges: 1) the increasing demand for a better quality of life and a better care of patients, 2) the need to transform public health care systems in more effective, efficient, equitable, accessible, and resilient ones and 3) the need to strengthen disease prevention and health promotion. In this view, ERA4Health objectives are: .SO1- Support relevant medical research including clinical fields and intervention areas (prevention, diagnosis, treatment) .SO2- Improve the utilisation of existing health technologies in clinical practice .SO3- Build capacity, in particular in conducting Investigator Initiated Clinical Studies at EU scale .SO4- Implement and advance the practice of RRI across the breadth of the programme ERA4Heatlth will be implemented in 2 phases: . Phase 1 (2 years) will implement joint calls focused on nutrition and lifestyle-related diseases, cardiovascular diseases and nanomedicine (4 in two years). In parallel, it will establish a supporting framework to overcome the challenges in launching international IICSs joint calls. . Phase 2, if the EC approves it: additional multinational calls for IICSs and joint calls for other priority areas will be launched in accordance with the decision of the Health Programme Committee taken at the end of previous Phase 34 partners (20 from EU, 3 Third Countries associated to HE and 2 non-associated, non EU), will commit 90,510,000€, during the 3 first years, as financial support to third parties. |
EVA-GLOBAL - European Virus Archive GLOBAL
Európsky vírusový archív GLOBAL
| Duration: | 1. 1. 2020 - 31. 12. 2023 |
| Evidence number: | 871029 |
| Program: | Horizont 2020 |
| Project leader: | RNDr. Klempa Boris DrSc. |
| Project web page: | https://www.european-virus-archive.com/ |
TRANSPAN - Identification of biological markers for prevention and translational medicine in pancreatic cancer
Identifikácia biologických markerov pre prevenciu a translačnú medicínu pri rakovine pankreasu
| Duration: | 11. 10. 2022 - 10. 10. 2026 |
| Evidence number: | CA21116 |
| Program: | COST |
| Project leader: | Mgr. Smolková Božena PhD. |
| Annotation: | Pancreatic cancer (PC) has a high mortality rate and is projected to become a massive public health problem in Europe. This Action will boost research on prevention of PC, particularly in the discovery of genetic risk factors, risk stratification, identification of biomarkers for early detection and patient monitoring, elucidation of biological mechanisms and functional pharmacogenomics for personalized medicine. These aims will be attained by expanding an existing interdisciplinary network. The Action will be organized in the following working groups: • Disease risk profiling. This WG will use germline genetic variants, epigenetics, transcriptomics and environmental factors to model disease risk and apply risk stratification scores to better select individuals eligible to be screened for PC or its precursors. • Non-invasive biomarkers. This WG will apply state-of-the-art liquid biopsies for the detection and characterization of circulating tumor cells and DNA, tumor-derived exosomes, tumor-educated platelets, epigenetic markers, and will test their diagnostic value for PC precursors and early-stage PC. • Tumor profiling. Genomic, epigenomic and transcriptional profiling of PC and its precursors in a multiregional analysis fashion will be used to identify novel biomarkers with prognosis and predictive value for PC patient stratification. • Functional genomics and therapy. This WG will functionally validate candidate genetic variants from germline or tumor studies by using cutting-edge approaches such as CRISPR-Cas9 gene editing. It will also generate novel approaches such as organoids / zebrafish avatars to implement (chemo)therapeutic strategies based on the patient in an effort to implement personalized medicine for PC. |
| Project web page: | https://www.cost.eu/actions/CA21116/ |
ISIDORe - Integrated Services for Infectious Disease Outbreak Research
Integrované služby pre výskum prepuknutia infekčných chorôb
| Duration: | 1. 2. 2022 - 31. 1. 2025 |
| Evidence number: | 101046133 |
| Program: | Horizont Európa |
| Project leader: | RNDr. Klempa Boris DrSc. |
TRANSLACORE - Translational control in Cancer European Network
Kontrola translácie v Cancer European Network
| Duration: | 4. 10. 2022 - 3. 10. 2026 |
| Evidence number: | CA21154 |
| Program: | COST |
| Project leader: | RNDr. Jurkovičová Dana PhD. |
Genome Editing to Treat Humans Diseases
Liečba chorôb modifikáciou genómu
| Duration: | 15. 9. 2022 - 14. 9. 2026 |
| Evidence number: | CA21113 |
| Program: | COST |
| Project leader: | prof. PharmDr. Ježová Daniela DrSc. |
HF-MetaB - Metabolic therapy of heart failure: which role for B vitamins
Metabolická terapia srdcového zlyhania: úloha vitamínov B
| Duration: | 1. 4. 2020 - 31. 3. 2024 |
| Evidence number: | ERA-CVD_JTC2019-055 |
| Program: | ERANET |
| Project leader: | RNDr. Zahradníková, ml. Alexandra PhD. |
| Annotation: | Heart failure (HF) is a major cause of death worldwide. It is clear that profound modulations of energy metabolism are involved in the development of HF. This includes a drop in the cardiac levels of energy carrier compounds, ATP, Phosphocreatine, and nicotinamide adenine dinucleotide (NAD+), a major coenzyme in glycolysis and mitochondrial ATP generation. In this respect we previously showed, in a mouse model of cardiac pressure overload, the protective effect of diet supplementation with two vitamins (B12/B9) stimulating the mitochondrial biogenesis pathways, or with nicotinamide riboside (NR), a recently characterized vitamin B3 which is a NAD+ precursor. Inasmuch as these treatments were given before the appearance of the first symptoms of HF in these studies, we propose here to test the efficiency of a treatment with a cocktail of these 3 B vitamins in symptomatic HF in mice to propose an eventual curative use of these vitamins. Our primary aim will be to assess the impact of treatment on survival, exercise capacities, cardiac function, mitochondrial respiration and dynamics, calcium metabolism and metabolic fluxes. In a translational perspective toward clinics, we will also assess the impact of this vitamins B cocktail in the context of standard of care of HF (β-blocker, ACE inhibitor). Finally, it is critically important to consider the sex differences in treatment of HF. Therefore the second aim of the presented project is to compare the effect of the treatment in males and females that differ as regards alteration in mitochondrial and calcium metabolism in HF. |
IMMUNO-model - Modelling immunotherapy response and toxicity in cancer
Modelovanie toxicity a odpovede na imunoterapiu pri liečbe rakoviny
| Duration: | 2. 11. 2022 - 1. 11. 2026 |
| Evidence number: | CA21135 |
| Program: | COST |
| Project leader: | Mgr. Smolková Božena PhD. |
| Annotation: | The IMMUNO-model COST Action aims to foster research and innovation in the field of preclinical immuno-oncology models with the ultimate goal of advancing in the treatment of cancer patients by improving their outcomes and quality of life. The unprecedented change that immunotherapy has represented in the treatment of cancer is best illustrated by the spectacular results obtained in previously incurable malignancies, such as metastatic melanoma. However, the widespread use of these therapies has been hindered by their limited effectiveness and associated toxicities. A better understanding on the complex interactions between tumor cells and the immune system is strictly required to address these problems, and to develop more effective and safer immunotherapies. However, one of the most important obstacles in immuno-oncology research is the scarcity of preclinical models that faithfully recapitulate human immunity and contribute to identify novel therapeutic targets, characterize biomarkers of therapeutic response and toxicity, and generate reliable data on drug synergies. IMMUNO-model will bring together European researchers from diverse sectors (academia, clinical, industry) with the common goal of establishing a Network that endorses immuno-oncology research by specifically promoting the sharing, standardization and application of immunotherapy preclinical models. |
| Project web page: | https://www.cost.eu/actions/CA21135/ |
Myokines and metabolically active molecules in the pathogenesis of idiopathic inflammatory myopathies
Myokíny a metabolicky aktívne molekuly v patogenéze idiopatických zápalových myopatií
| Duration: | 1. 5. 2021 - 31. 12. 2024 |
| Evidence number: | NU21-05-00322 |
| Program: | Iné |
| Project leader: | prof. MUDr. Ukropcová Barbara PhD. |
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
| Duration: | 1. 7. 2019 - 31. 1. 2024 |
| Evidence number: | NEURON II/2018/569/UNMET |
| Program: | ERANET |
| Project leader: | prof. PharmDr. Ježová Daniela DrSc. |
RESCUER - Resistance under treatment in breast cancer
Rezistencia po liečbe u karcinómu prsníka
| Duration: | 1. 8. 2020 - 31. 5. 2024 |
| Evidence number: | ID: 39 |
| Program: | ERANET |
| Project leader: | Mgr. Cihová Marína PhD. |
| Annotation: | The concept behind this project is that by computational algorithms and mathematical modelling integrating data from clinical trials, ex vivo experimental models, and tumor molecular data at multiple levels will lead to the identification of drivers of resistance. These will be incorporated into patient-specific therapeutic regimens in a systems medicine approach. A leading edge of RESCUER is combining state-of-art mathematical modeling to data obtained from clinical trials and cutting-edge cell models to discover patientspecific therapeutic regimens. The efficacy in overcoming resistance will be evaluated by treating patient-derived xenograft (PDX) models derived from treatment resistant breast cancer (BC) patients prior to forthcoming clinical trials aimed to enroll patients with resistant tumors will be designed. The investigation and discovery of effective treatments for subclasses of BC can be performed only upon a deep understanding of intra-patient and inter-tumor heterogeneity and of the mechanisms of treatment resistance |
TBFV - TBFVnet: surveillance and research on tick-borne flaviviruses
TBFVnet: sledovanie a výskum flavivírusov prenášaných kliešťami
| Duration: | 1. 7. 2020 - 31. 1. 2024 |
| Evidence number: | 2018-1-0659 |
| Program: | Iné |
| Project leader: | RNDr. Klempa Boris DrSc. |
TENTACLES - TEmperature-responsive Nanogels for TArgeted delivery of miCroRNAs in wound heaLing and tissue rEgeneration applicationS
Tepelne senzitívne nanogély pre cielený transport miRNA na liečbu rán a regeneráciu tkanív
| Duration: | 1. 2. 2020 - 31. 1. 2024 |
| Program: | ERANET |
| Project leader: | RNDr. Šramková Monika PhD. |
| Annotation: | The development of new therapeutically active wound protection agents, which not only protect the injured skin from external influences but also support the healing process itself, has significant potential for clinical applications. The aim of the TENTACLES project is to develop an innovative multifunctional nanogel that integrates protective (nanohydrogel) and healing functions (iron oxide nanoparticles and targeted miRNAs) within one nanocomposite intelligent structure. The nanohydrogel fulfills a protective function, while the iron oxide nanoparticles, due to mild hyperthermia, promote the induction of HSP (heat shock protein) and miRNAs, which play a key role in the healing process of wound healing. The innovative nanocomposite nanohydrogel provides a revolutionary wound healing strategy, especially for diabetic patients. |
| Project web page: | https://www.tentacles-enm3.eu/ |
Role of the CA IX ectodomain in tumor growth and metastasis
Úloha ektodomény CA IX v nádorovom raste a metastázovaní
| Duration: | 11. 11. 2014 - 31. 12. 2023 |
| Program: | Iné |
| Project leader: | prof. RNDr. Pastoreková Silvia DrSc. |
| Annotation: | This project is aimed at understanding the role of the CA IX ECD in tumor growth and metastasis in vivo using mouse models. We intend to evaluate growth of tumor xenografts (following subcutaneous implantation of tumor cells) and colonization of lungs (following injection of tumor cells into the tail vein) in absence and presence of the recombinant CA IX ECD. In addition, we plan to evaluate potential therapeutic targeting of CA IX ECD through analysis of the anticancer effect of antibodies binding to different regions of the ectodomain, including M75 and VII/20. Particularly M75 is of great interest, because the N-terminal PG region, to which M75 binds, was recently found to be involved in cell adhesion and spreading, the processes contributing to metastatic dissemination. On the other hand, MAb VII/20 binds to the central CA catalytic domain and was previously shown to reduce the growth of primary tumors, but its effect on metastasis has not been examined so far. Thus, we expect that the project will allow us to dissect the role of ECD in metastasis and propose antibody-based therapeutic strategies to reduce metastatic growth. |
VACCELERATE - VACCELERATE - European Corona Vaccine Trial Accelerator Platform
VACCELERATE - Európska platforma na akceleráciu klinického skúšania vakcín proti novému koronavírusu
| Duration: | 28. 1. 2021 - 27. 1. 2024 |
| Evidence number: | H2020-IBA-SC1-CORONAVIRUS-2020-4-ID: 101037867 |
| Program: | Horizont 2020 |
| Project leader: | prof. RNDr. Pastoreková Silvia DrSc. |
| Annotation: | The COVID-19 pandemic has underscored the need for concerted efforts towards vaccine development in Europe. The EU-funded VACCELERATE project creates a platform connecting all European vaccine development stakeholders. VACCELERATE maps clinical trial and laboratory sites across Europe and identifies the best locations for conducting Phase 2 and 3 vaccine trials. A Volunteer Registry provides access to trial participants. The network coordinates laboratory support and provides standardised assays and trial protocols. VACCELERATE identifies and shares emerging public health questions, provides answers through its own clinical trials, and lends expertise and tangible support to vaccine developers from industry and academia. With these efforts, VACCELERATE partners are creating a network ready to face emerging pandemics and enhance vaccine development capacity in Europe. |
| Project web page: | https://vaccelerate.eu |
National Projects
Nano-Neuro-Plast - Activation of the VGF/BDNF/TrkB pathway by synthetic mRNA encapsulated in polyplex nanoparticles: effects on neural excitability, neuroplasticity and animal behavior
Aktivácia VGF/BDNF/TrkB dráhy syntetickou mRNA zapúzdrenou v polyplexových nanočasticiach: účinky na nervovú excitabilitu, neuroplasticitu a správanie zvierat
| Duration: | 1. 7. 2021 - 30. 6. 2025 |
| Evidence number: | APVV-20-0202 |
| Program: | APVV |
| Project leader: | prof. PharmDr. Ježová Daniela DrSc. |
Analysis of the virome complexity and intra-species diversity from agricultural and wild plants in various agroecological contexts.
Analýza komplexnosti a vnútrodruhovej diverzity virómu poľnohospodárskych a divorastúcich druhov rastlín z rôznych agroekologických kontextov.
| Duration: | 1. 1. 2020 - 31. 12. 2023 |
| Evidence number: | VEGA2/0030/20 |
| Program: | VEGA |
| Project leader: | Ing. Glasa Miroslav DrSc. |
| Annotation: | The recent introduction of new generation sequencing (NGS) into plant virus research has significantly altered the view on the complexity of plant viral infections while opening up new possibilities for study of plant virome. The project focuses on virome analysis using NGS, with samples coming from a variety of agroecological contexts potentially affecting the complexity of infections (perennial and annual agricultural species and wild plants). In addition to the potential identification of new viruses or highly divergent forms of known viruses, we will evaluate the genetic diversity of pathogens and the involved evolutionary mechanisms, as important factors for pathogen adaptation to the host. Genomic data will be used to analyze intraspecific molecular diversity and viral population polymorphism. Using variants-specific detection tools, the frequency and competitiveness of viral variants in mixed infections under natural and experimental conditions and their epidemiological consequences will be monitored. |
Analysis of peripheral nerve regeneration after transection on the model of rat caudal nerve using tubulization and mesenchymal stem cells.
Analýza regenerácie periférneho nervu po transekcii na modeli kaudálneho nervu potkana s využitím tubulizačných techník a mezenchýmových kmeňových buniek.
| Duration: | 1. 1. 2021 - 31. 12. 2023 |
| Evidence number: | 2/0109/21 |
| Program: | VEGA |
| Project leader: | RNDr. Blaško Juraj PhD. |
| Annotation: | Injury of the peripheral nerve with a consequent limitation/loss of function is due to the nature of the nervous system a longterm problem in the field of medicine. Our aim in this project is to precisely quantify the extent of regeneration of a rat peripheral nerve after transection and application of tubular conduit bridging the site of injury after long term survival period (4-12 weeks). Based on our preliminary results and established method of nerve tubulization we want to focus on the identification of critical distance between two stumps of transected nerve in which regeneration still occurs. Our previous results have shown that if two nerve stumps are placed in a conduit and are oriented in a thight contact, axons of proximal stump grow into distal stump and partial re-connection occurs. In the last phase of the project we will test the potential of mesenchymal stem cells enriched conduits in the regeneration of peripheral nerve. |
CoViD - Antiviral drugs against COVID-19: Design, synthesis and biological activity testing of specific inhibitors of viral proteases of coronavirus SARS-CoV-2
Antivirálne liečivá proti COVID-19: Dizajn, syntéza a testovanie aktivity špecifických inhibítorov virálnych proteáz koronavírusu SARS-CoV-2
| Duration: | 1. 7. 2022 - 30. 6. 2026 |
| Evidence number: | APVV-21-0108 |
| Program: | APVV |
| Project leader: | Mgr. Nemčovičová Ivana PhD. |
| Annotation: | The pandemic of the new coronavirus SARS-CoV-2, which causes serious diseases of the respiratory tract (COVID-19), poses a long-term threat to human health. The vaccination of the population with available vaccines in Slovakia is low and currently only one broad-spectrum antiviral drug - remdesivir, which is targeted to viral RNA polymerase, has been approved for the treatment of COVID-19. Our team, based on many years of experience in designing new antiviral agents (e. g. against HIV-1, HCV, Dengue, influenza A virus), has been intensively researching viral protease inhibitors since the beginning of the COVID-19 pandemic. targeted against the main protease Mpro and papain-like protease PLpro of SARS-CoV-2 virus, which are among the key pharmacological targets for antiviral therapy. The presented project builds on our previous results, which combine competencies from five experienced groups of researchers from two universities (FaF and PriF UK, UCM), together with CHÚ SAV and VÚ BMV SAV. The project strategy is based on the following integrated approach to drug research: • Computer-assisted design and optimization of specific peptidomimetic α-ketoamides that inhibit the proteolytic activity of Mpro; optimization of two series of bis-benzylidenecyclohexanones and benzamides that inhibit the proteolytic and deubiquitination activity of PLpro for the coronavirus SARS-CoV-2. • Development of synthetic routes and synthesis of peptidomimetic α-ketoamides, benzamides and bis- benzylidenecyclohexanones. • Testing for inhibition of enzymatic activity of three groups of substances on recombinantly prepared enzymes Mpro and PLpro and development of new methods for testing inhibitory activity on viral enzymes. • In vitro antiviral activity testing of three groups of substances at the level of inhibition of human cell lines infected with SARS-CoV-2 virus. • Research into the interactions of new inhibitors with biological membranes and the optimization of absorption and bioavailability. |
MyeLon - Bacterial Lon protease as an emerging tool for multiple myeloma treatment
Bakteriálna Lon proteáza ako perspektívny nástroj na liečbu mnohopočetného myelómu
| Duration: | 1. 7. 2022 - 30. 6. 2026 |
| Evidence number: | APVV-21-0215 |
| Program: | APVV |
| Project leader: | RNDr. Jakubíková Jana PhD. |
GLYCO4BIO - Biochip systems for targeted glycan analysis of biomarkers for biomedical and biotechnological applications
Biočipové systémy na cielenú glykánovú analýzu biomarkerov pre biomedicínske a biotechnologické aplikácie
| Duration: | 1. 7. 2021 - 30. 6. 2025 |
| Evidence number: | APVV-20-0243 |
| Program: | APVV |
| Project leader: | Mgr. Nemčovičová Ivana PhD. |
| Annotation: | The GLYCO4BIO project focuses on research and development of analytical systems based on microarray biochips enabling targeted and high-throughput glycoprofiling and their use in biomedicine and biotechnology. This is a strongly interdisciplinary research with a high degree of innovation, especially in the field of construction and application of original biochip devices on the microarray platform. New systems for analyzing glycan structures in various types of biological samples will be developed, verified and validated, such as a high-performance microfluidic reflectometric label-free microarray system, and an on-chip glycoprofiling platform combining microarray and MS technology. The expected benefit of the presented project is mainly in the development of innovative biochip systems for targeted glycorecognition based on modern technologies and their use in biomedicine, biotechnology, the study of biointeractions and in the analysis and screening of biomarkers. The systems will be applied, for example, in the research and detection of biomarkers of congenital disorders of glycosylation (CDG), cancer, gestational diabetes, in oncological research, as well as in the development and characterization of the therapeutic proteins. The developed biochip systems significantly outperform traditional techniques and have a high potential for their translation into clinical analysis. The expected results of the project will improve and expand the possibilities of diagnostics and therapy, and significant benefits are also expected in the expansion of knowledge in the field of biomedical research, glycoproteomics and biotechnology. |
Exercise in prevention & treatment of chemotherapy-related late toxicity in testicular germ cell cancer survivors: the role of skeletal muscle
Cvičenie v prevencii a liečbe neskorej toxicity chemoterapie u vyliečených onkologických pacientov: úloha kostrového svalstva
| Duration: | 1. 1. 2020 - 31. 12. 2023 |
| Evidence number: | 2/0164/20 |
| Program: | VEGA |
| Project leader: | Mgr. Ukropec Jozef DrSc. |
| Annotation: | Regular exercise is effective in prevention & treatment of chronic diseases. Exercise can reduce late toxicity of chemotherapy, commonly found in cancer survivors, which is yet to be translated into clinical practice. Mechanisms of exercise benefits in oncologic patients are far from being elucidated, and include increase in muscle mass, reduction of fat mass, systemic inflammation and cardiometabolic risk. Synchronization of exercise adaptive response is, to an extent, mediated by bioactive molecules released from muscle, with antiinflammatory & tumor-suppressing properties. Muscle satellite cells are a source of regeneration, muscle structural integrity & funcional capacity. Phenotypes of muscle cells, such as secretory profile, lipid & glucose metabolism, mirror clinical phenotypes of the donor. Importantly, muscle cells’ metabolism in vitro can be modulated by 8-12 week training in vivo. Epigenetic mechanisms regulating muscle & systemic metabolism in cancer survivors are not yet understood. |
Cytokine profiling together with carbonic anhydrase IX immunotargeting as a promising tool in diagnostics and treatment of pancreatic cancer
Cytokínové profilovanie v spojení s imunotargetingom karbonickej anhydrázy IX ako perspektívny nástroj v diagnostike a liečbe rakoviny pankreasu
| Duration: | 1. 7. 2021 - 30. 6. 2025 |
| Evidence number: | APVV-20-0480 |
| Program: | APVV |
| Project leader: | Mgr. Švastová Eliška PhD. |
Detailed analysis and elucidation of functions of Cka1 and Ksg1 protein kinases using the conditional ATP analog-sensitive mutants
Detailná analýza a objasnenie funkcie Cka1 a Ksg1 proteínkináz využitím ich kondičných na ATP analógy citlivých mutantov
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0021/22 |
| Program: | VEGA |
| Project leader: | Ing. Čipák Ľuboš PhD. |
Detection of the tick borne-encephalitis virus in milk of farm animals by LAMP method as the prevention of alimentary infections
Detekcia vírusu kliešťovej encefalitídy v mlieku hospodárskych zvierat metódou Lamp ako prevencia alimentárnych infekcií
| Duration: | 1. 1. 2022 - 31. 12. 2024 |
| Evidence number: | 2/0126/22 |
| Program: | VEGA |
| Project leader: | RNDr. Ličková Martina PhD. |
| Annotation: | Tick-borne encephalitis (TBE) is a serious viral neurological disease caused by the tick-borne encephalitis virus (TBEV). TBEV is maintained in nature in a cycle involving the virus, ticks as vectors, and small mammals as hosts. Humans are infected through tick bites, as the main route of transmission; or by alimentary route after the consumption of raw milk of infected goats and sheep. Slovakia has the highest number of TBE foodborne diseases in Europe. The presented project aims to develop a quick test for TBEV detection in milk, intended for use directly at the sampling point. The test will be based on the LAMP method, which we adapt specifically for TBEV detection in milk. We will examine samples of sheep's and goat's milk from Slovak farms as well as milk samples of sheep and goats infected in the laboratory (cooperation with FLI in Germany). Milk samples will be also evaluated by the RT-qPCR. The project results will help to improve the safety of the consumption of unpasteurized dairy products. |
Diagnostic of oncological diseases using aptasensors: development and validation
Diagnostika onkologických ochorení pomocou aptasenzorov: vývoj a validácia
| Duration: | 1. 1. 2021 - 31. 12. 2024 |
| Evidence number: | 2/0160/21 |
| Program: | VEGA |
| Project leader: | Mgr. Bábelová Andrea PhD. |
| Annotation: | DNA aptamers, also referred to as DNA antibodies, are short single-stranded sections of DNA that form spatial structures that allow high-affinity to interact with receptors and other biomolecules. The project aims to develop and validate a new diagnostic method that utilizes the unique affinity properties of DNA aptamers for the early detection of cancer. In terms of project aims, we will analyze the molecular mechanisms of interactions between DNA aptamers and specific markers found on the surface of the tumor cells. We plan to use a sensitive method of quartz microbalances (QCM), which allows real-time monitoring of interactions. For practical use, we plan to prepare conjugates of selected aptamers and gold nanoparticles depending on their physicochemical parameters and their interaction with neoplastic cells. We have the ambition to identify factors currently limiting the wider use of aptamers and aptamer-modified nanoparticles in clinical practice and contribute to their elimination. |
Diversity of vector-borne pathogenic and non-pathogenic microorganisms and potential therapy of zoonotic diseases caused by them
Diverzita vektormi prenášaných patogénnych a nepatogénnych mikroorganizmov a potenciálna terapia nimi spôsobených zoonotických ochorení
| Duration: | 1. 1. 2021 - 31. 12. 2024 |
| Evidence number: | 2/0021/21 |
| Program: | VEGA |
| Project leader: | Mgr. Špitalská Eva PhD. |
| Annotation: | Tick-borne zoonotic infections are among the most spread vector-borne diseases, they are caused by different microorganisms, such as tick-borne encephalitis virus, Rickettsia spp., Coxiella burnetii, Ehrlichia spp., Borrelia spp., Francisella tularensis, Babesia spp. Changes in the incidence of ticks cause changes in the incidence of vector-borne pathogens and the development of new outbreaks making them constantly at the center of attention. Tick microbiome includes not only pathogens but also various symbionts, interacting with each other. In the era of increasing antibiotic resistance, there is a need for alternative methods of treatment, which could be photodynamic therapy at an early stage of infection. The proposed project is focused on the study of pathogens and symbionts present in their vector, the host, to explain their mutual influence, genetic diversity, incidence, prevalence and to test the possibility of using photodynamic therapy to treat tick-borne infections in vitro. |
Ecology of West Nile virus in globally changing environment
Ekológia West Nile vírusu v prostredí ovplyvnenom globálnou zmenou
| Duration: | 1. 1. 2021 - 31. 12. 2024 |
| Evidence number: | 2/0140/21 |
| Program: | VEGA |
| Project leader: | RNDr. Čabanová Viktória PhD. |
Exosomes secreted by cancer cells of digestive organs, their characterization and modification by the CRISPR/Cas9 system for the aim of use in therapy
Exozómy vylučované bunkami nádorov tráviaceho traktu, ich charakterizácia a modifikácia CRISPR/Cas9 systémom s cieľom ich využitia na terapiu
| Duration: | 1. 1. 2021 - 31. 12. 2024 |
| Evidence number: | 2/0178/21 |
| Program: | VEGA |
| Project leader: | RNDr. Kozovská Zuzana PhD. |
| Annotation: | The Extracellular exosome-type vesicles (30-150 nm) secreted by tumor cells reflect the nature of the tumor. They are able to regulate the stemnes of tumor cells, create a premetastatic niche in the target organs of future metastasis, transmit chemoresistance and their genetic content can be altered by modifying of the cells from which they are secreted. Using the CRISPR/Cas9 gene editing technique, we will change in cancer cell lines key genes associated with exosome biogenesis, targeting of exosomes to the site of the premetastatic niche (lungs and liver), the activation of the epitelial-mesenchymal transition and with the stemnes required for metastasis of the primary tumor. From these edited cell lines we will isolate exosomes which we will apply to chemoresistant tumor cells to test the rate of their proliferation, migration. In vivo we will test the ability of exosomes from an edited and control cancer cell line to prevent the formation of metastases. |
CA(9)NNIBAL - Cell-in-cell phenomena as microevolutionary processes in cancer progression: a role for hypoxia-induced carbonic anhydrase IX
Fenomény “bunka v bunke” ako mikroevolučné procesy v nádorovej progresii: úloha hypoxiou-indukovanej karbonickej anhydrázy IX
| Duration: | 1. 7. 2020 - 30. 6. 2024 |
| Evidence number: | APVV-19-0098 |
| Program: | APVV |
| Project leader: | prof. RNDr. Pastoreková Silvia DrSc. |
| Annotation: | Cell-in-cell phenomena refer to situations, in which tumor cells (“winner cells”) engulf one or more viable cells (“loser cells”) to gain nutrients in periods of starvation. Such cell-in-cell structures have been observed in human tumors for decades, but the underlying mechanisms and relevance to cancer progression has remained largely unexplored. Emerging view on molecular and functional aspects of cell-in-cell phenomena suggests their involvement in microevolutionary processes that occur in highly heterogeneous tumor tissues and lead to selection of aggressive tumor cells. Despite increasing interest in cell-in-cell phenomena, their understanding still remains fragmentary. In this project, we aim to elucidate the contribution of hypoxia and acidosis in tumor microenvironment to two cell-in-cell processes, namely cell cannibalism and entosis, with particular focus on carbonic anhydrase IX (CA IX), which plays a key role in pH regulation as an adaptive response of tumor cells to hypoxia and oncogenic metabolism. To achieve this aim, we intend to employ state-of-the-art approaches of molecular and cell biology and experimental oncology, and to use unique CA IX expertise and specific reagents developed by our team since our discovery of CA IX. According to our working hypothesis, CA IX participates in induction of cell-in-cell structures and is associated with “winner” phenotype enabling tumor cells to sustain starvation, survive microenvironmental stresses and gain aggressive properties. We also hypothesize that CA IX does so via participation in metabolic rewiring, morphological plasticity, intercellular signalling and protection of tumor cells from hypoxia and acidosis. Finally, we propose that hypoxia and acidosis are microenvironmental stimuli that trigger formation of cell-in-cell structures and thereby accelerate microevolution in tumor tissue. These hypotheses are supported by preliminary results and implicit evidences from our published and unpublished data. |
| Project web page: | - |
Genetics of rare forms of diabetes with focus on functional characterization of new variants
Genetika vzácnych foriem diabetu s dôrazom na funkčnú charakterizáciu nových variantov
| Duration: | 1. 1. 2021 - 31. 12. 2024 |
| Evidence number: | VEGA 2/0131/21 |
| Program: | VEGA |
| Project leader: | RNDr. Škopková Martina PhD. |
| Annotation: | Diabetes mellitus significantly affects both quality of life and life expectancy and it's etiology determines correct treatment. In HNF1A-MODY, insulin can be replaced with tablets and, after confirmation of GCK-MODY, no treatment is needed at all. Still, however, a large proportion of people with MODY does not have a proper diagnosis. In part of them, a DNA variant of unknown significance has been identified. This project is dedicated to the determination of pathogenicity of new variants in genes for the transcription factor HNF1A and for the GCK glucokinase using functional studies. Impact on DNA binding, transactivation and intracellular localization will be assessed in case of variants in the HNF1A gene. Variants affecting splicing in any gene will be analysed using mini-gene essays. The project will contribute to the knowledge about the structure of these genes, with results being directly applied to clinical practice, as it will allow to adapt therapy in patients with a confirmed pathogenic variant. |
Herpesviral immunomodulators as novel candidates in therapy of cancer and inflammatory diseases
Herpesvírusové imunomodulátory ako noví kandidáti na liečbu rakoviny a zápalov
| Duration: | 1. 1. 2021 - 31. 12. 2024 |
| Evidence number: | 2/0063/21 |
| Program: | VEGA |
| Project leader: | RNDr. Lopušná Katarína PhD. |
LEONORA - Verification of clinically relevant biomarkers for the stratification of CRC patients by molecular and bioinformatic methods.
Hľadanie klinicky relevantných biomarkerov pre stratifikáciu CRC pacientov použitím molekulárnych a bioinformatických metód.
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0170/22 |
| Program: | VEGA |
| Project leader: | Ing. Poturnajová Martina PhD. |
| Annotation: | The Slovak Republic has the second highest incidence and mortality from colorectal cancer (CRC) in the world. 50% of patients develop metastases and 40% of stage II-III patients relapse within 5 years after surgical treatment. Research therefore focuses on identifying high-risk patients using new prognostic biomarkers. In the project we will analyze the expression of newly discovered long non-coding RNAs (lncRNAs), their correlation with disease prognosis, chemoresistance and metastasis and verify the possibility of their use as a prognostic biomarker of the disease. The results could enable to define the risk groups of CRC patients with a worse prognosis or indicate the treatment decision between a more radical vs. gentle therapy for an individual patient. Linking applied research with the needs of the clinical oncology using the latest biostatistical and bioinformatics methods allows us to approach the personalized treatment of CRC patients. |
NeuroSocial - Characterization of excitatory and inhibitory neurons in the brain areas relevant for development of social behaviour in the autism-related model
Charakterizácia excitačných a inhibičných neurónov v oblastiach mozgu doležitých pre vývin sociálneho správania v modeli autizmu
| Duration: | 1. 7. 2022 - 30. 6. 2025 |
| Evidence number: | APVV-21-0189 |
| Program: | APVV |
| Project leader: | doc. RNDr. Bakoš Ján PhD. |
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Charakterizácia nových proteínov podieľajúcich sa na regulácii zostrihu pre-mRNA
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Program: | VEGA |
| Project leader: | Ing. Čipáková Ingrid PhD. |
TESTOX - Identification and validation of biomarkers and underlying molecular pathways of late toxicity of curative treatment in testicular germ cell tumors
Identifikácia a validácia biomarkerov a zodpovedných molekulárnych dráh neskorej toxicity kuratívnej liečby u germinatívnych nádorov testis
| Duration: | 1. 7. 2020 - 30. 6. 2024 |
| Evidence number: | APVV-19-0411 |
| Program: | APVV |
| Project leader: | prof. MUDr. Ukropcová Barbara PhD. |
| Annotation: | Testicular germ cell tumors (GCTs) are a unique malignancy with a long-term cure rate > 95%. The implementation of multi-modality treatment with cisplatin-based chemotherapy, radiotherapy and surgery have rendered GCTs as model for cancer cure. Growing population of GCT survivors can suffer from late toxicity of treatment, ultimately leading to lower quality of life, increasing long-term morbidity and early mortality. Among the known late toxic sequelae are secondary malignancies, cardiovascular toxicity, neurotoxicity, nephrotoxicity, pulmonary toxicity, hypogonadism, infertility, cognitive dysfunction, sexual function impairment and decline in quality of life. Proposed project aims to further develop ongoing programme of late toxicity research in National Cancer Institute in Slovakia. The project will focus on longitudinal assessment of distinct types of late toxicities and identify biomarkers and underlying molecular mechanisms. Two interventional randomized studies will be conducted to assess the effects of endurance and strength training. This project is the first state-of-the-art approach to implement comprehensive joined clinical and translational research with an attempt to identify and further analyse late toxicity of anti-cancer treatment also integrating the programme for prevention. The project is also considered to be a pilot comprehensive programme for survivorship initiatives and research applicable among other cancer types. |
Identification of etiology in sporadic forms of hereditary hearing loss by whole exome sequencing
Identifikácia etiológie sporadických foriem dedičnej poruchy sluchu pomocou sekvenovania novej generácie
| Duration: | 1. 1. 2021 - 31. 12. 2024 |
| Evidence number: | 1/0572/21 |
| Program: | VEGA |
| Project leader: | RNDr. Gašperíková Daniela DrSc. |
INCAM - Identification of novel biomarkers linked to the relapse of metastatic colorectal cancer after metastasectomy
Identifikácia nových biomarkerov spojených s relapsom metastatického kolorektálneho karcinómu po metastasektómii
| Duration: | 1. 7. 2022 - 30. 6. 2026 |
| Evidence number: | APVV-21-0296 |
| Program: | APVV |
| Project leader: | RNDr. Matúšková Miroslava PhD. |
| Annotation: | Colorectal cancer (CRC) belong to the most frequent malignancies worldwide. Approximately 20% of CRC patients are diagnosed with liver metastases at the time of primary tumour diagnosis. The liver is the most frequent site of metastases and often the only organ affected. After liver metastasis resection, 5-year overall survival rates range 31–60%. Nevertheless, 50–75% of patients experience recurrence after surgery, and the majority of such recurrences occur within 2 years. Furthermore, over half of the patients die within five years following resection. Despite many studies focused on clinical outcome prediction were conducted, there is still a need for a reliable biomarker to predict poor prognosis. We propose that the benefit of surgical removal of liver metastases in CRC patients is strongly dependent on the genetic and expression signature of malignant tissue. The metastasectomy represents a highly invasive procedure that should be preceded by non-invasive examination, e.g. by examination of circulating nucleic acids (liquid biopsy) from peripheral blood. We aim to identify a credible biomarker or set of biomarkers in patients’ plasma and correlate them with the time of relapse after liver metastasis removal. Using high-throughput DNA and RNA sequencing we will identify novel candidate biomarkers, evaluate their clinical relevance by biostatistical methods and determine the functional effect of selected biomarker(s) in vitro and in vivo. Functional analysis will be performed in engineered patient-derived organoids and patient-derived xenografts, which represent innovative up to date preclinical models recapitulating the clinicopathological traits and genetic profiles of the original patient’s tumour tissue. |
REZTEST - Identification of new treatment options in refractory testicular germ cell tumors
Identifikácia nových možností liečby u refraktérnych testikulárnych nádorov zárodočných buniek
| Duration: | 1. 7. 2021 - 30. 6. 2025 |
| Evidence number: | APVV-20-0158 |
| Program: | APVV |
| Project leader: | Mgr. Kučerová Lucia DrSc. |
| Annotation: | Testicular germ cell tumors (TGCTs) are the most common tumors in young males with increasing incidence in Slovakia and resemble the clinical and biological characteristics of a model for the cure of cancer. Nonetheless, a small proportion of patients does not have a durable complete remission with initial cisplatin-based chemotherapy. Only 20–40% of them can be cured with the use of platinum-containing standard-dose or high-dose salvage chemotherapy with autologous stem cell transplantation. Patients who fail to be cured after second-line salvage therapy have an extremely poor prognosis and long-term survival had been documented in <5%. Numerous new treatment regimens, including targeted and biological therapies, have been evaluated in patients with refractory TGCT, however, with very limited efficacy. The aim of this project is to identify new therapeutic targets in chemorefractory disease using high-throughput methods of molecular biology through translational research and to identify new drugs that overcomes cisplatin resistance. |
Identification of potential therapeutic targets associated with cisplatin resistance in yolk sac tumors
Identifikácia potenciálnych terapeutických cieľov asociovaných s rezistenciou voči cisplatine u nádorov zo žĺtkového vaku
| Duration: | 1. 1. 2021 - 31. 12. 2024 |
| Evidence number: | 02/0124/21 |
| Program: | VEGA |
| Project leader: | Mgr. Kučerová Lucia DrSc. |
Individuálna rádiosenzitivita onkologických pacientov a využitie Gingko biloba na prevenciu vedľajších účinkov rádioterapie
Individual radiosensitivity of cancer patients and use of Gingko biloba in the prevention of radiotherapy induced side effects
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | 2/0079/23 |
| Program: | VEGA |
| Project leader: | Mgr. Durdík Matúš PhD. |
| Annotation: | Severe side effects are present in ?5% of cancer patients treated with radiotherapy (RT) while no relevant method for assessment of individual radiosensitivity is clinically available. We will perform in vitro radiation-induced apoptosis assay and in vivo cytokinesis blocked micronuclei (CBMN) and chromosomal aberrations (CA) assay with the aim to detect radiosensitive (RS) patients before the RT. We will compare the radiation response of RS and normal responding patients in vitro using the analysis of radiation-induced DNA repair foci, CBMN and CA. Gingko biloba is an ancient plant with strong antioxidant capabilities and its extract could be used in the protection from RT-related healthy tissue side effects in breast cancer patients. The goal is to validate the appropriate combination of techniques for detecting the RS patients, to study the potential protective effect of Gingko biloba extract and the effect of previous COVID-19 infection on the RT-related healthy tissue side effects in cancer patients. |
Individual radiosensitivity of cancer patients and use of Gingko biloba in the prevention of radiotherapy induced side effects
Individuálna rádiosenzitivita onkologických pacientov a využitie Gingko biloba na prevenciu vedľajších účinkov rádioterapie
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | 2/0079/23 |
| Program: | VEGA |
| Project leader: | MSc. Abbasi Pashaki Pejman |
| Annotation: | Severe side effects are present in ?5% of cancer patients treated with radiotherapy (RT) while no relevant method for assessment of individual radiosensitivity is clinically available. We will perform in vitro radiation-induced apoptosis assay and in vivo cytokinesis blocked micronuclei (CBMN) and chromosomal aberrations (CA) assay with the aim to detect radiosensitive (RS) patients before the RT. We will compare the radiation response of RS and normal responding patients in vitro using the analysis of radiation-induced DNA repair foci, CBMN and CA. Gingko biloba is an ancient plant with strong antioxidant capabilities and its extract could be used in the protection from RT-related healthy tissue side effects in breast cancer patients. The goal is to validate the appropriate combination of techniques for detecting the RS patients, to study the potential protective effect of Gingko biloba extract and the effect of previous COVID-19 infection on the RT-related healthy tissue side effects in cancer patients. |
Inhibition of Carbonic Anhydrase IX (CA IX) Circumventing Cisplatin Resistance in Refractory Testicular Germ Cell Tumours
Inhibícia karbonickej anhydrázy IX (CA IX) ako nástroj prekonania rezistencie voči cisplatine u refraktérnych testikulárnych nádorov zo zárodočných buniek
| Duration: | 1. 1. 2021 - 31. 12. 2023 |
| Evidence number: | 1/0349/21 |
| Program: | VEGA |
| Project leader: | RNDr. Matúšková Miroslava PhD. |
RENASTHERA - Novel renal antisense therapy platform for CKD
Inovatívna antisense terapeutická platforma pre CKD - chronické ochorenie obličiek
| Duration: | 1. 8. 2021 - 30. 6. 2025 |
| Evidence number: | APVV-20-0494 |
| Program: | APVV |
| Project leader: | Mgr. Bábelová Andrea PhD. |
| Annotation: | Chronic kidney disease (CKD) with its progressive nature towards end-stage renal disease (ESRD) is a lethal and rapidly progressing severe health complication associated with significantly decreased quality of life and high mortality rates. Strikingly, despite the progress made in early-diagnostics of CKD, state-of-the-art therapeutics do not significantly decrease the risk of renal and cardiovascular morbidity and mortality rates in CKD patients which remain devastatingly high. This fact highlights an urgent need not only for novel therapeutics but also for the implementation of progressive experimental and clinical tools into translational drug discovery. In this context, the proposed RENASTHERA project offers a novel therapeutic solution to stop progressive renal function loss. This solution is based on a patented method of nucleic acid inhibition. Periostin, a 90 kDa secreted protein was identified as a key player in CKD development, inhibition of which effectively prevented CKD progression. The design, synthesis, and functional validation of an RNA inhibitor specifically designed for periostin RNA is thus the clearly defined scope of the proposed RENASTHERA project. |
COXHOST - Host cell interaction with Coxiella burnetii: identification and utilization of novel therapeutic and diagnostic targets
Interakcia hostiteľských buniek s Coxiella burnetii: identifikácia a využitie nových terapeutických a diagnostických cieľov
| Duration: | 1. 7. 2020 - 30. 6. 2024 |
| Evidence number: | APVV-19-0519 |
| Program: | APVV |
| Project leader: | Ing. Škultéty Ľudovít DrSc. |
| Annotation: | Coxiella burnetii is an intracellular bacterial pathogen causing human infections of clinical and public health relevance. As many other bacterial pathogens, Coxiella uses specialized secretion systems to manipulate eukaryotic host cells by injection of effectors (bacterial virulence proteins and small molecules). However, current knowledge about how these pathogens establish infection is limited. The central research commitment of this project is the characterization of the functions of effector proteins from Coxiella burnetii. The project’s specific objectives include: 1) the description of the host cell signaling pathways targeted by effectors (proteins and small molecules) of Coxiella burnetii; 2) the characterization of the molecular and cellular mode of action of the effectors, and 3) a putative correlation between the mode of action of the effectors to their sequence variability and expression amongst different strains. The anticipated results may lead to the discovery of novel therapeutic approaches-drug targets- and could help in the design of vaccines and novel diagnostics. In particular, the host signaling pathways altered by one (or more) effector(s) will be promising candidates as novel therapeutic targets. Furthermore, the knowledge that will be gained could also lead to the identification of inhibitors targeting the pathogen’s effectors directly and help to design specifically drugs that can block the secretion system of the pathogen. |
Interaction of bioactive compounds and non-thermal plasma
Interakcie bioaktívnych látok a nízkoteplotnej plazmy
| Duration: | 1. 1. 2021 - 31. 12. 2024 |
| Evidence number: | 1/0460/21 |
| Program: | VEGA |
| Project leader: | Mgr. Horváthová Eva PhD. |
CATCA - Interactions of calcium transport systems in carcinogenesis
Interakcie vápnikových transportných systémov v karcinogenéze
| Duration: | 1. 7. 2021 - 30. 6. 2025 |
| Evidence number: | APVV-20-0176 |
| Program: | APVV |
| Project leader: | prof. Ing. Križanová Oľga DrSc. |
Is hypoxia a master modulator of DNA repair capacity and mitochondrial dynamics in chemotherapy response in urogenital malignancies?
Je hypoxia kľúčovým modulátorom DNA reparačnej kapacity a metabolizmu mitochondrií v odpovedi testikulárneho karcinómu na chemoterapiu?
| Duration: | 1. 1. 2021 - 31. 12. 2024 |
| Evidence number: | 2/0056/21 |
| Program: | VEGA |
| Project leader: | RNDr. Jurkovičová Dana PhD. |
| Annotation: | Testicular germ cell tumors (TGCT) are cisplatin (CDDP) well treatable malignancy, with excellent response even in advanced metastatic stages. 20-30% of patients do not respond, relaps, and have a poor prognosis due to CDDP resistance. Several mechanisms are responsible for tumor cell resistance, leading the tumor cell to survive and avoid apoptosis. In the proposed project we will focus on: 1) DNA repair mechanisms contributing to the resistance increased capacity of DNA damage repair and 2) metabolism of mitochondria (dynamics, mitophagy) whose changes are critical for the cell response to induction of cell death. In the resistance of TGCT and other solid tumors, hypoxia and associated epigenetic modulation (by miRNA and methylation) are believed to be the key regulators. On TGCT cell lines we will focus on DNA damage and repair and selected mitochondrial proteins, and we will try to identify signaling pathways where HIF-1α and miRNA are the major regulators of these changes. Our aim is to identify and validate early molecular markers informing about CDDP resistance of TGCT patients before treatment initiation. |
Carbonic anhydrase IX: one of the key components of exosomes secreted from cancer cells
Karbonická anhydráza IX: jeden z kľúčových komponentov exozómov sekretovaných z nádorových buniek
| Duration: | 1. 1. 2020 - 31. 12. 2023 |
| Evidence number: | 2/0074/20 |
| Program: | VEGA |
| Project leader: | RNDr. Zaťovičová Miriam CSc. |
| Annotation: | Knowledge of the cellular processes that govern exosome biology is essential to shed light on the physiological and pathological functions of these vesicles, as well as for clinical applications. Current evidence suggests that exosomes participate in many key tumor-promoting processes. The subject of the proposed project is the exosome-located, tumor-associated protein carbonic anhydrase IX (CA IX), and implication of this enzyme’s extracellular form in many processes, such as its role in the tumor microenvironment, cancer metastasis, and in cancer immunity. We will use not only the latest in vitro cell biology methods in the project, including real-time cell parameter measurements but also in vivo experiments. Results of this project are expected to extend our knowledge on function of CA IX located in exosomes as an important cancer cell messenger, as well as a potential clinical biomarker. |
ACE2MAS - Cardiometabolic effects of Mas receptor stimulation by modulation of the renin-angiotensin system - the key role of angiotensin-converting enzyme 2.
Kardiometabolické účinky stimulácie Mas receptorov modulovaním renín-angiotenzínového systému - klúčová úloha angiotenzín-konvertujúceho enzýmu 2.
| Duration: | 1. 7. 2021 - 30. 6. 2025 |
| Evidence number: | APVV-20-0421 |
| Program: | APVV |
| Project leader: | Ing. Zorad Štefan CSc. |
| Annotation: | The renin-angiotensin system (RAS) is a hormonal cascade whose chronic activation contributes to the development of cardiovascular pathologies caused mainly by remodeling of the heart and blood vessels. It is becoming apparent that the benefit of RAS inhibitors includes, in addition to Ang II inhibition, stimulation of the alternative arm of RAS mediated by the ACE2/Ang1-7/Mas receptor, which has vasodilatory, antiproliferative, anti-inflammatory and metabolic effects. The aim of the present project will be to compare the effect of ACE inhibition, AT1 blockade, stimulation of ACE2 (diminazene) and Mas receptor (cyclic Ang1-7, alamandine) in a model of old, obese, diabetic hypertensive Zucker rats with a focus on the potential benefit of Ang1-7/Ang1-5 on glucose utilization, insulin signal transduction, reduction of the inflammatory response and function of the cardiovascular system. Given the potentially key role of RAS and especially ACE2 in the development of acute respiratory distress syndrome (ARDS) and the severe course of COVID-19, the aim of the present project will be to detect changes in membrane and serum ACE2 and expression of other key molecules for viral infection (ADAM17, TMPRSS2, furin and B0AT1 transporter) using various pharmacological interventions. The dependence of the putative alterations on the activity of the Mas receptor will be monitored by its specific antagonist A779. In vitro, following treatment of human alveolar cells and adipocyte cultures with RAS and diminazene inhibitors, the changes in the ability to bind SARS-CoV-2 virus will be assessed using a pseudoviral methodology. The obtained results might contribute to the elucidation of the role of ACE2 and Mas receptor in the pathogenesis of obesity and diabetes. The project might also contribute to the clarification of the choice of an effective RAS inhibitor in the elderly with a combination of hypertension, obesity and diabetes. |
CARDIOEND - CARDIOvascular protection mediated by α1AMPK against metabolic syndrome-mediated ENdothelial Dysfunction – identifying new risk factors
Kardiovaskulárna ochrana sprostredkovaná α1AMPK proti endotelovej dysfunkcii sprostredkovanej metabolickým syndrómom – identifikácia nových rizikových faktorov
| Duration: | 1. 7. 2023 - 30. 6. 2027 |
| Evidence number: | APVV-22-0154 |
| Program: | APVV |
| Project leader: | RNDr. Hlaváčová Nataša PhD. |
| Annotation: | Disruption of vascular homeostasis caused by decreased nitric oxide bioavailability oxide due to oxidative stress and inflammation is the most serious complication of metabolic syndrome (MetS), leading to increased morbidity and mortality. There is an unmet need to identify key factors that prevent or protect vascular endothelium and thus improve primary and secondary prevention of cardiovascular diseases. It appears that AMP-dependent protein kinase (AMPK) may be such a factor. Its protective properties and positive effect on endothelial function and oxidative stress are already known. These unique properties suggest that AMPK may be involved in improving metabolic control during MetS, but still, the molecular changes due to α1AMPK-related dysregulation during MetS development are poorly understood. The project focuses on risk factors affecting endothelial function during MetS and the AMPK as a potential tool to modify those risk factors resulting in MetS prevention or treatment. The originality of the project is based on a comprehensive evaluation of functional, molecular, and biochemical changes in endothelial function, inflammation, and metabolic senescence during MetS with a detailed focus on vascular endothelium - proliferation, senescence, and apoptosis. The focus will be put on risk factors affecting endothelial function such as the interaction/adhesion of leukocytes with the vascular endothelium and the AMPK-dependent role of erythrocytes during MetS development. The project will be enriched by the study of phenotypic and molecular changes at the level of the CNS, with an emphasis on neuroinflammation and behavioral changes. Importantly, the project has a translation character, as human studies in patients with MetS will also be performed. The obtained results may represent a potential tool for improving the current population’s health and reducing the economic burden associated with the treatment of this cardiometabolic disease. |
Checkpoint molecules and viral immunomodulators in cancer therapy
Kontrolné body a vírusové immunomodulatory v nádorovej terapii
| Duration: | 1. 9. 2022 - 31. 8. 2025 |
| Evidence number: | 1136/01/02 |
| Program: | SASPRO |
| Project leader: | RNDr. Lopušná Katarína PhD. |
Lactate, a metabolic signal and energy fuel driving alternative thermogenic mechanisms
Laktát, metabolický signál a zdroj energie pre alternatívne termogénne mechanizmy
| Duration: | 1. 2. 2022 - 31. 1. 2025 |
| Evidence number: | 1148/01/02 |
| Program: | SASPRO |
| Project leader: | Mgr. Baláž Miroslav PhD. |
The mechanism of action of virus-specific cross-reactive antibodies on dual infection with influenza virus and bacteria
Mechanizmus účinku vírus-špecifických krížovo-reaktívnych protilátok na duálnu infekciu vírusom chrípky a baktériami
| Duration: | 1. 1. 2021 - 31. 12. 2024 |
| Evidence number: | 2/0090/21 |
| Program: | VEGA |
| Project leader: | RNDr. Tomčíková Karolína PhD. |
Mechanisms of glutamate metabolism as a tool of ischemic tolerance
Mechanizmy metabolizácie glutamátu ako nástroj ischemickej tolerancie
| Duration: | 1. 1. 2021 - 31. 12. 2023 |
| Evidence number: | VEGA 2/0073/21 |
| Program: | VEGA |
| Project leader: | RNDr. Bonová Petra PhD. |
| Annotation: | The role of glutamate in the CNS changes diametrically under the pathological conditions associated with ischemia. Its neurotoxic effect (excitotoxicity) is one of the basic parameters determining the resulting range of infarction of the brain. Induction of the ischemic tolerance is manifested by low levels of extracellular glutamate in the brain, which is probably related to significant neuroprotection. However, the mechanisms of glutamate metabolism activated in the tolerant phenotype remain unclear. |
MitoHF - Mitochondrial disease in heart failure
Mitochondriálne ochorenia a zlyhanie srdca
| Duration: | 1. 7. 2022 - 30. 6. 2026 |
| Evidence number: | APVV-21-0443 |
| Program: | APVV |
| Project leader: | RNDr. Zahradníková, ml. Alexandra PhD. |
| Annotation: | Several mutations in mitochondrial genes of respiratory chain proteins are associated with heart failure (HF). The extent of their contribution to the development of HF at the level of cardiomyocytes (CM) is unknown. Recent findings indicate that various HF etiologies share similar remodeling of CM, especially of their membrane system and calcium signaling. The project is aimed to validate the in vitro model of HF development in a genetic disorder with reduced function of mitochondrial respiratory chain and to verify at the cellular level prevention of HF development by metabolic therapy with nutritional supplements. We will use the HL-1 CM cell line with allotopic expression of a mutant form of the MT-ND5 gene for subunit 5 of respiratory complex I (mG13513A), associated with human hypertrophic cardiomyopathy, to determine the impact of diseased mitochondria on cytoarchitecture and contractile function of cardiac myocytes. By methods of electron and confocal microscopy, cell electrophysiology, oxygraphy, and molecular biology, we will monitor expression and localization of dyadic proteins and changes in mitochondrial structure, localization, and oxidative capacity. Since genetic cardiomyopathy cannot yet be addressed by gene therapy, we will investigate the benefits of metabolic therapy for the compensation of invalidated mitochondrial function. We will compare in HL-1 CM the effect of the hereditary mitochondrial insufficiency with that of HF development imposed by overstimulation. We expect that nutritional supplementation of mitochondrial function will improve CM performance and suppress the development of HF. Results will be published in leading experimental cardiology and physiology journals and publicize them on the projec t website and in the media. Three PhD students and several M.S. students will participate in the project. |
| Project web page: | http://confolab.sav.sk/ovsb/projekty/aktivne-projekty/apvv-21-0443/ |
LEGOMICS - Modern "omics" approaches as effective tools for identification and characterization of leguminous viral pathogens
Moderné "omics" postupy ako efektívne nástroje pre identifikáciu a charakterizáciu vírusových patogénov strukovín
| Duration: | 1. 7. 2021 - 30. 6. 2025 |
| Evidence number: | APVV-20-0015 |
| Program: | APVV |
| Project leader: | Ing. Glasa Miroslav DrSc. |
| Annotation: | Legumes (the Fabaceae family) represent a nutritionally and economically important crop, important for human and livestock nutrition. However, the quality and quantity of legume production can be adversely affected by a complex of viral pathogens. Available knowledge on the presence, epidemiology and diversity of phytopathogenic legume viruses in field conditions, collections of long-term genetic resources and wild-type Fabaceae species in Slovakia are insufficient. The aim of the presented project is unbiased and accurate identification of the viruses present on legumes and subsequent genomic characterization of pathogens in our territory using modern sequencing approaches. The data obtained will be used to develop effective detection methods and targeted molecularepidemiological studies taking into account the regional diversity of pathogens, including seed-borne infectious agents. The susceptibility of selected legume genotypes to viral infection is evaluated by experimental inoculation with characterized virus isolates. The mutual interaction of selected genotypes of legumes and the investigated biotic pathogen will be analyzed by modern methods of cellomic research including next generation sequencing (genomics, transcriptomics) and the proteome will be studied by classical immunochemical methods in combination with modern analytical-chemical methods based on mass spectrometry (LC-MS / MS, nanoLC-ESI-Q-TOF). By combining these currently most progressive methods in plant virology, we obtain accurate and detailed data necessary for the most comprehensive evaluation of the pathogen / plant relationship. The methodological platform used, using modern and efficient genomic, transcriptomic, proteomic and in silico procedures, will provide important knowledge for the diagnosis and characterization of viral diseases and also knowledge for improving the quality of legume cultivation in Slovakia. |
Modulation of individual types of IP3 receptors in carcinogenesis and their impact on the effect of chemotherapeutics
Modulácie jednotlivých typov IP3 receptorov a ich vplyv na účinok chemoterapeutík
| Duration: | 1. 1. 2022 - 31. 12. 2024 |
| Evidence number: | 2/0040/22 |
| Program: | VEGA |
| Project leader: | prof. Ing. Križanová Oľga DrSc. |
IZOTIOVIVO - Molecular mechanisms of trialkyl-/triaryltin isothiocyanates' and carboxylates' antitumour properties - novel ligands of nuclear retinoid X receptors in rat mammary gland carcinomas and human tumour cell lines
Molekulárne mechanizmy protinádorových vlastností trialkyl- /triarylcíničitých izotiokyanátov a karboxylátov, nových ligandov jadrových retinoidných X receptorov v karcinómoch mliečnej žľazy potkana a v ľudských nádorových bunkách prsníka
| Duration: | 1. 7. 2021 - 30. 6. 2025 |
| Evidence number: | APVV-20-0314 |
| Program: | APVV |
| Project leader: | Mgr. Macejová Dana PhD. |
| Annotation: | Organometallic compounds, on account of their structural diversity, are applied in human oncology in the treatment of cancer. Triorganotin derivatives showed significant cytotoxic properties. At the cellular level, they induce massive cell death in various types of cell cultures even at low concentrations and are able to activate the processes of apoptotic pathways, in which several molecular mechanisms play a role. A significant breakthrough in knowledge was our recent experimental confirmation of the ability of molecules of triorganotin compounds to bind to nuclear retinoid X receptors, and thus function as potent agonists. The aim of the present project is to investigate the in vivo effects of tributyl/triphenyltin isothiocyanates in the process of chemical carcinogenesis of the mammary gland of female rats, which is based on our current results of in vitro experiments. Simultaneously, the research of antitumour properties of triorganotin compounds activating RXR-RAR heterodimers comprising novel RXR agonists based on triorganotin carboxylates, is envisaged. In vitro analyses of molecular mechanisms leading to inhibition of tumour cell growth or induction of apoptosis in the presence/absence of natural ligands of RAR receptors on human breast tumour cell lines: MCF-7 (non-invasive, ER positive), T47D (ER positive), MDA-MB-231 (invasive, triple negative) and MDA-MB-436 (invasive, ER negative, PR negative), will be accomplished. We also plan to achieve new data on the possible endocrine disruption of triorganotin compounds on the murine TM3 cell line and the human COV434 cell line representing the reproductive system. We assume that the presented project will gain new and original knowledge about the mechanism of the action of the studied substances through their binding and activation of nuclear receptors, their transactivation as well as crosslink with other signalling pathways that may contribute to the development of novel treatment options for breast cancer. |
Molecular regulatory mechanisms and therapeutic potential of retinoid X receptor activation by triorganotin compounds in relation to breast cancer treatment
Molekulárne regulačné mechanizmy a terapeutický potenciál aktivácie retinoidných X receptorov triorganocíničitými zlúčeninami vo vzťahu k liečbe nádorových ochorení prsníka
| Duration: | 1. 1. 2021 - 31. 12. 2023 |
| Evidence number: | 2/0116/21 |
| Program: | VEGA |
| Project leader: | Mgr. Macejová Dana PhD. |
| Annotation: | Tributyl/triphenyl tin (TBT/TPT) compounds are organic tin derivatives characterized by covalent bonds between the three carbon atoms and the tin atom. TBT/TPT as environmental pollutants can cause DNA damage. Exposure to triorganotins in mammals results in immunosuppressive, metabolic, reproductive and developmental disorders through binding to retinoid X receptors. Triorganotin derivatives have shown cytotoxic properties against tumour cell lines. The aim of the present project is to study the role of these compounds in the processes of transactivation of retinoic acid-induced transcription factor regulatory signals, the mechanism of action of these compounds through their potential endocrine disruption, and their possible induction of apoptosis and inhibition of invasive tumour cell proliferation and migration. The results obtained will be reflected in the "design" of in vivo experiments using an experimental model of mammary carcinogenesis to evaluate the benefit/risk ratio of therapy. |
WOLPACMUT - Mutations associated with Wolfram syndrome: alternative signaling pathways for calcium and mitochondrial physiology
Mutácie asociované s Wolframovým syndrómom: rozdielne signálne dráhy v zmysle metabolizmu vápnika a funkcie mitochondrií
| Duration: | 1. 7. 2022 - 30. 6. 2026 |
| Evidence number: | APVV-21-0473 |
| Program: | APVV |
| Project leader: | RNDr. Cagalinec Michal PhD. |
| Annotation: | Wolfram syndrome (WS), characterized by diabetes insipidus, diabetes mellitus, optical atrophy and deafness, is caused by mutations in WFS1 gene. Protein WFS1 is highly expressed in the brain and pancreas where its mutations are in line with the symptoms. Moreover, a high expression has been observed in the heart; however, in the vast majority of WS cases the cardiac symptoms have not been reported. WFS1 is localized in the membrane of endoplasmic reticulum (ER) and strongly impacts calcium metabolism, mitochondrial function and ER stress. However, the principal question about WFS1 function still remains open – why the pancreatic β-cells and neurons are affected severely in WS, and why are the alterations in myocytes jut minor, when WFS1 is highly expressed in them? Possible explanation could be a yet unresolved compensatory mechanism present in myocytes and/or a different signalling pathway(s) when compared to neurons/ β-cells. Therefore, the first hypothesis is: Do the calcium metabolism and mitochondrial dynamics differ in cardiac myocytes when compared to neurons and pancreatic β-cells in case of WFS1 malfunction? The majority of WS cases represent recessive mutations; however, several dominant mutations have been identified as well. Therefore the second hypothesis is: Do the calcium metabolism and mitochondrial dynamics differ in cells expressing pathogenic dominant vs. recessive Wfs1 mutations? Moreover, complete novelty of the project represents characterization of the heterozygous WFS1 deletion variant recently identified in the first Slovak WS patient at the applicant’s institute. Use of up-to-date approaches including CRISPR/Cas9 gene editing, optogenetic techniques, confocal microscopy and the know-how of the proposed research team will help to resolve the WFS1 function which will serve for development of early diagnostics and effective treatment not only for WS, but also for diabetes mellitus and highly prevalent cardiovascular diseases. |
| Project web page: | http://confolab.sav.sk/ovsb/projekty/aktivne-projekty/apvv-21-0473/ |
iMMunoedit - Cancer immunoediting in multiple myeloma: immune checkpoints and clinical significance
Nádorové imunoeditovanie v mnohopočetnom myelóme: imunitné kontrolné body a klinický význam
| Duration: | 1. 8. 2021 - 30. 6. 2025 |
| Evidence number: | APVV-20-0183 |
| Program: | APVV |
| Project leader: | RNDr. Jakubíková Jana PhD. |
| Annotation: | The understanding of cancer immunoediting, immune defense mechanisms against cancer, has been challenging in multiple myeloma (MM). A hallmark of the myeloma microenvironment is profound immune dysregulation and loss of immune surveillance. The overall objective is to characterize immunoediting in MM using cellular and molecular approaches. We will focus on understanding the complex innate and adaptive immune systems during the development of MM: from premalignant conditions MGUS and smoldering MM to symptomatic MM. We will define diverse immune checkpoint mechanisms and their biological sequelae on tumor promoting/suppressing immune subsets within the tumor microenvironment together with MM cells as well as blockage role of novel immune checkpoint inhibitors in ex vivo. Moreover, we will define the impact of anti-MM therapies on modulation of MM immunoediting in a homogeneously treated cohort of MM patients, allowing us to evaluate the impact of suppressed immune system on emergence of resistant tumor clones; and vice versa. MM immunoediting of primary patient samples together with immune checkpoint mechanisms, including regulatory co-stimulation/tumor antigen/checkpoint molecules and signaling pathways, will be evaluated using mass cytometry. These studies will identify mechanisms and biologic sequelae of immunoediting in MM, and provide for rational design of targeted and immune therapy in MM. |
Design and optimization of bioconjugation strategies of innovative 2D photothermal nanomaterials with tumor-targeting peptides
Návrh a optimalizácia biokonjugačných stratégií inovatívnych 2D fototermálnych nanomateriálov s tumornavádzajúcimi peptidmi
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0117/22 |
| Program: | VEGA |
| Project leader: | Mgr. Strapcová Sabína |
Newly syntethized thymol derivatives: relationship between structure and biological activity in colorectal in vitro model.
Novosyntetizované deriváty tymolu: vzťah medzi štruktúrou a biologickou aktivitou na in vitro modeli čreva.
| Duration: | 1. 1. 2020 - 31. 12. 2023 |
| Evidence number: | 2/0055/20 |
| Program: | VEGA |
| Project leader: | RNDr. Kozics Katarína PhD. |
| Annotation: | Beneficial effects of thymol (TY), a naturally occurring phenol monoterpene of essential oil from thyme, on human health are well known for many years. It is widely used in medical practices, cosmetics, agriculture and as a natural remedy. However due to its low solubility in aqueous media its use e.g. in food industry is limited. The proposed project is focused on the synthesis of hydrophilic derivatives of TY while the antioxidative and antiproliferative properties as well as the effective cellular uptake will remain intact. Using comprehensive approaches from biochemistry, biology, and molecular biology will enable us to assess the biological effects of these derivatives depending on their molecular structure. The project will contribute to gain an insight into the molecular mechanisms of action of hydrophilic TY derivatives. The biological activity will be studied using 2D and 3D colorectal cell models cultured in vitro. |
Unraveling the role of genetic predispositions in the context of breast cancer tumor microenvironment
Objasnenie úlohy genetických predispozícií v kontexte nádorového mikroprostredia karcinómu prsníka
| Duration: | 1. 1. 2020 - 31. 12. 2023 |
| Evidence number: | VEGA/2/0138/20 |
| Program: | VEGA |
| Project leader: | Mgr. Cihová Marína PhD. |
Unraveling the mechanisms linking obesity and cancer progression: the interplay between adipocytes and cancer cells
Odhalenie mechanizmov spájajúcich obezitu s nádorovou progresiou: interakcia medzi adipocytmi a nádorovými bunkami
| Duration: | 1. 1. 2020 - 31. 12. 2023 |
| Evidence number: | 2/0076/20 |
| Program: | VEGA |
| Project leader: | RNDr. Takáčová Martina PhD. |
| Annotation: | Obesity is a major public health concern because it increases the risk of several diseases, including cancer. Crosstalk between obesity and cancer seems to be very complex, potentially acting directly on cells, or indirectly via changes in the tumor microenvironment. One of the proposed mechanisms underlying the risk association is the adipocyte-mediated secretion of adipokines. Adipokines, acting locally or systemically, play important roles in the growth, local invasion, metastatic spread, and resistance to treatment of different types of cancer. Therefore, a great interest exists to understand the molecular mechanisms by which adipocytes contribute to carcinogenesis. This project will examine on the impact of adipokines on the biological characteristics of cancer cells exposed to hypoxia and/or acidosis, focusing on carbonic anhydrase IX that is a well-known marker of tumor hypoxia, expression of which significantly correlates with poor prognosis and resistance to therapy. |
A pilot study of the selective effects of a new generation of RNA interfering agents at the cellular level
Pilotná štúdia selektívneho pôsobenia novej generácie RNA interferenčných agens na bunkovej úrovni
| Duration: | 1. 1. 2020 - 31. 12. 2023 |
| Evidence number: | 1/0069/20 |
| Program: | VEGA |
| Project leader: | Mgr. Jakič Kristína PhD. |
| Annotation: | The proposed project is based on the in-depth understanding of the current scientific and clinical knowledge of chronic myelogenous leukemia (CML) and the therapeutic regimens based on RNA interference. The project aims at a highly ambitious goal: to explore the selective effect of a novel platform of RNA interfering agents at the cellular level in order to evaluate its therapeutic potential for action without side effects that would result from undesired molecular interactions. From this perspective, the project focuses primarily on an extensive study of cellular internalization, inhibition of the formation of fusion BCR-ABL1 protein, selectivity of RNA interfering agents towards the target mRNA and its effect in cells resistant to currently applied therapeutics. |
Comparison between silibinin-conjugated gold nanospheres and nanobipyramids impacts on the treatment of liver fibrosis in vivo.
Porovnanie účinku nanosfér a nanobipyramíd zlata konjugovaných so silibinínom pri liečbe fibrózy pečene in vivo.
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0116/22 |
| Program: | VEGA |
| Project leader: | Mgr. Svitková Barbora PhD. |
| Annotation: | Liver fibrosis occurs as a result of chronic liver damage associated with the accumulation of extracellular matrix proteins. It is the common outcome of various infectious and non-infectious diseases and represents a global health problem resulting from the high global prevalence and limited treatment options. Treatment of liver fibrosis is essential to prevent the development of liver cirrhosis and hepatocellular carcinoma, however, there is no effective pharmaceutical intervention to date for the treatment of this disease. One of the promising but yet barely explored approach to treat the liver fibrosis is offered by the targeted therapy using nanomaterials coated with an antifibrotic drug. In case of inorganic nanomaterials, spherical gold nanomaterials are being investigated for this aim. Interestingly nanomaterials of other shapes (e.g. nanobipyramids) could possess even better diagnostic and therapeutic features due to their unique physical-optical properties. |
KINSPL - Post-translational regulation of pre-mRNA splicing factors
Posttranslačná regulácia faktorov zostrihu pre-mRNA
| Duration: | 1. 7. 2021 - 30. 6. 2024 |
| Evidence number: | APVV-20-0141 |
| Program: | APVV |
| Project leader: | Ing. Čipák Ľuboš PhD. |
PRO4CML - Preclinical validation of an innovative antisense platform for CML
Predklinická validácia inovatívnej antisense platformy pre CML
| Duration: | 1. 7. 2020 - 30. 6. 2024 |
| Evidence number: | APVV-19-0070 |
| Program: | APVV |
| Project leader: | Mgr. Bábelová Andrea PhD. |
| Annotation: | Currently, chronic myelogenous leukemia (CML) is widely treated with tyrosine kinase inhibitors (TKIs) that effectively inhibit proleukemic activity of the causal BCR-ABL oncoprotein. However, long-term clinical experience with TKIs shows that these drugs are not sufficiently selective and specific for CML cells and BCR-ABL, respectively. This phenomenon often results in clinically significant adverse events responsible for deterioration of TKI treatment outcomes and decreased quality of life. Moreover, limited therapeutic effect of TKIs towards CML stem cells cause that patients with CML are in most of the cases long-term treated, but not completely cured. The development of alternative treatment strategies that exclusively target only CML cells and provide a possibility of permanent cure, is therefore of paramount need. The proposed PRO4CML project is directly related to the successful APVV-15-0215 project (total IF of the scientific output > 80), which was aimed at testing of an innovative antisense concept for BCR-ABL silencing in patients with CML. Thanks to its original design and mechanism of action, this progressive concept showed unprecedented potential in terms of selective recognition of target nucleic acid and, most importantly, exceptional translational potential in terms of selective biological action exclusively in tumor cells. Since the conceptual solution is fully universal, it is expected to overcome the major obstacles that have so far hindered antisense therapeutics from entry to clinical practice. The PRO4CML project is thus a natural continuation of the scientific work of the project consortium and represents the cornerstone for robust in vivo preclinical validation. If successful, the proposed concept is also expected to provide an original therapeutic platform not only in CML but also in other diseases with known molecular basis, where a particular protein plays a causal role in disease pathophysiology. |
VALERIA - Preclinical validation of a SARS-CoV-2-specific RNA inhibitor
Predklinická validácia špecifického RNA inhibítora proti SARS-CoV-2
| Duration: | 1. 7. 2022 - 30. 6. 2024 |
| Evidence number: | APVV-21-0220 |
| Program: | APVV |
| Project leader: | Mgr. Bábelová Andrea PhD. |
| Annotation: | The persistent worldwide paralysis caused by the SARS-CoV-2 coronavitus fundamentally affects an individual´s life in every aspect. Moreover, the global dimension of this crisis is exacerbated by the fact that it has long gone beyond medicine and public health and has resulted in a complex problem with apparent negative effects on the economy. Regardless of widespread consequences of this crisis, the common denominator and cause remains the SARS-CoV-2 virus itself, the safe neutralization or elimination of which is perhaps the most burning scientific and research challenge today. There is currently no specific therapeutic solution against SARS-CoV-2, which is a clearly defined prioritiy for the effective fight against virus. The VALERIA projekt naturally aims to leverage on the current scientific work and bring a safe and functional antiviral agent for direct translation into clinical practice. |
HeaTME - Reprogramming pancreatic ductal adenocarcinoma microenvironment towards immunotherapy
Preprogramovanie mikroprostredia duktálneho adenokarcinómu pankreasu voči imunoterapii
| Duration: | 1. 7. 2022 - 30. 6. 2026 |
| Evidence number: | APVV-21-0197 |
| Program: | APVV |
| Project leader: | Mgr. Smolková Božena PhD. |
| Annotation: | Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a 5-year survival below 10%. Although immune checkpoint inhibitors revolutionized cancer treatment, PDAC patients still do not benefit from immune therapies. This lack of response, which mainly resides in the low immunogenicity and non-inflamed nature of PDAC, can be predicted, in part, from the immune phenotypes present in the tumor microenvironment (TME). These aspects raise a primary clinical question: How to prime these "cold" tumors into "hot" and responsive to immunotherapy? Recently, epigenetic regulators have been shown to drive the immunosuppressive cancer microenvironment by silencing critical components of the antigen-presenting machinery, cytokines, or chemokines. Therefore, epigenetic reprogramming has emerged as one of the promising strategies to promote the immunogenicity of tumor cells. We hypothesize that distinct cell population subgroups in the PDAC TME, manifested by markers and intrinsic cell-cell communication networks yet to be discovered, can be targeted by epigenetic drugs (epi-drugs) to facilitate PDAC treatment and response to immunotherapy. The project HeaTME aims to increase understanding of the complexity and heterogeneity of PDAC TME by identification, integration, and mechanistic evaluation of critical TME elements driving PDAC drug resistance. The intent is to adopt comprehensive tumor-TME research models to identify, characterize and introduce novel, biology-backed targets involved in modulating multi-directional TME dynamics. The implementation of new strategies, such as spatial transcriptomics, will provide innovative comprehensive assessment of treatment -induced TME reprogramming and expose new vulnerabilities that will inform the design and testing of more effective epi -drug-based combination approaches aiming to reprogram PDAC towards immunotherapy. |
Génové manipulác - Preparation of new antibiotics and antitumor agents by manipulations of secondary metabolite genes and synthetic biology methods
Príprava nových antibiotík a protinádorových látok manipuláciami génov sekundárnych metabolitov a metódami syntetickej biológie
| Duration: | 1. 7. 2020 - 30. 6. 2024 |
| Evidence number: | APVV-19-0009 |
| Program: | APVV |
| Project leader: | RNDr. Jakubíková Jana PhD. |
Radiation-induced noncoding RNAs in mononuclear cells of umbilical cord blood
Radiačne-indukované nekódujúce RNA v mononukleárnych bunkách pupočníkovej krvi
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0084/22 |
| Program: | VEGA |
| Project leader: | RNDr. Škorvaga Milan CSc. |
| Annotation: | Noncoding RNAs (ncRNAs), including circular RNAs (circRNAs) and long ncRNAs (lncRNAs) are involved in regulation of gene expression in eukaryotic cells at the transcriptional and posttranscriptional level. Studies revealed that circRNA and lncRNA expression was altered by medium-dose IR, however, it is unknown whether they are regulated by low-dose IR. In this project, we wish to study the level of the expression of circRNAs (circPvt1, circSPRY2, KIRKOS-71, KIRKOS-73) and that of lncRNAs (lncMALAT1, lncGAS5), after exposure to low-dose IR and radiofrequency (RF) radiation in umbilical cord blood mononuclear cells (UCB MNCs). In addition, two recurrent Pvt1 chimeric transcripts, generated as posttranscriptional events, will be monitored in IR/RF exposed UCB MNCs. NcRNAs significantly deregulated in UCB MNCs by radiation will be applied for screening of peripheral blood of radiologists. This work is aimed at evaluating the potential of analyzed ncRNAs as biodosimetry markers of low-dose IR and RF radiation. |
Plant systems for transient expression of peptidic substances as a tool for preparation of anti-viral vaccines
Rastlinné systémy pre tranzientnú expresiu látok peptidovej povahy za účelom prípravy vakcín proti vírusovým ochoreniam
| Duration: | 1. 1. 2022 - 31. 12. 2024 |
| Evidence number: | 2/0003/22 |
| Program: | VEGA |
| Project leader: | RNDr. Šubr Zdeno CSc. |
| Annotation: | Vectors based on Plum pox virus (PPV) genome will be applied for the expression of antigens originating from medically important viruses (Influenza A virus, SARS-CoV-2) in a model plant species Nicotiana benthamiana and also in other herbaceous and woody PPV hosts. In the case of free polypeptide expression, we will optimize its production and subsequent extraction and purification from plant tissues. Regarding the production of virus-like particles (VLPs) expressing the antigenic molecule on its surface, we will focus on the determination of cloning capacity of the relevant vector (maximum insert size), or the impact of insert localization and sequence on the infectivity of resulting construct, as well as its purification from plant material. |
Regulation of M1/M2 polarization: the effect on neuron survival, axonal growth and functional recovery after spinal cord trauma
Regulácia M1/M2 polarizácie: vplyv na prežitie neurónov, rast axónov a funkčnú obnovu po poranení miechy
| Duration: | 1. 1. 2021 - 31. 12. 2023 |
| Evidence number: | 2/0145/21 |
| Program: | VEGA |
| Project leader: | RNDr. Lukáčová Nadežda DrSc. |
| Annotation: | Proposed project is aimed to 1) study molecular changes that regulate transformation of neuroinflammatory M1 microglia to A1 astrocytes in acute/subacute phase after Th9 compression, 2) characterize time-dependent regulation of M1/M2 polarization, a key factor in activation of pro-regenerative molecules, 3) investigate selected markers for identification of pro-inflammatory cytokines, infiltration of M1/M2 macrophages, activation of resident cells (astrocytes and microglia) and infiltration of lymphocytes in the spinal cord, blood serum and in the small intestine after Th9 compression and antibiotics, probiotics and anti-inflammatory treatment. To determine which of mechanisms regulates M1/M2 polarization, and which signaling pathways (P13K/Akt; PLC-γ/CAMK a PLC-γ/PKC) are responsible for neuroplasticity and cells survival. To investigate neuroregenerative and neuroprotective effect of treatment on tissue integrity, axonal sprouting, synaptic activity and functional recovery in chronic stage of SCI. |
NEUROGEN - Neurotransmitter-mediated regulation of postnatal neurogenesis in the rat olfactory system under physiological and pathological conditions
Regulácia postnatálnej neurogenézy v čuchovom systéme potkana prostredníctvom neurotransmiterov za fyziologických a patologických podmienok
| Duration: | 1. 7. 2020 - 30. 6. 2024 |
| Evidence number: | APVV-19-0279 |
| Program: | APVV |
| Project leader: | RNDr. Račeková Enikö CSc. |
| Annotation: | The regulatory mechanisms of postnatal neurogenesis in the olfactory neurogenic area of the mammalian brain - the subventricular zone (SVZ), rostral migratory stream (RMS) and olfactory bulb (OB) are still not fully understood. The project is focused on investigation of neurogenesis regulation via neurotransmitters nitric oxide and serotonin in this neurogenic region under physiological conditions and in rat model of depression. We intend to reveal neuronal circuits of nitric oxide producing neurons localized within the rat RMS, which should contribute toward the understanding of neuronal regulation of postnatal neurogenesis. To date, the association between decreased serotonin levels due to depression and reduced neurogenesis has been demonstrated only in the hippocampus. Our experiments are aimed to investigate the link between depression, altered serotonin regulation and neurogenic processes in the olfactory neurogenic area. Detailed analysis of integral components of microenvironment in the SVZ in animals with induced depression enables us to reveal the processes of regulation of neurogenesis in pathologically altered conditions. New knowledge in this area could potentially reveal promising targets for novel therapies aimed to disorders associated with changes in adult neurogenesis. |
Dyad remodelling in cardiomyocytes in experimental therapy of failing heart
Reorganizácia diád kardiomyocytov pri experimentálnej terapii zlyhávajúceho srdca
| Duration: | 1. 1. 2021 - 31. 12. 2024 |
| Evidence number: | 2/0182/21 |
| Program: | VEGA |
| Project leader: | RNDr. Zahradníková, ml. Alexandra PhD. |
| Annotation: | Heart failure is a prominent cause of death in contemporary society. The development of heart failure is accompanied by marked changes in the energetics of the myocardium. Therapy by a cocktail of B vitamins, targeted at mitochondrial energetics, showed a promising cardioprotective effect on the development and progression of heart failure. However, it is not known to what extent does the protection result from remodelling of the calcium signalling systems. Our aim is to identify the relationship between the structural dynamics of dyads, the quality of excitation-contraction coupling, and the changes of junctophilin expression in a model of cardiac pressure overload in mouse. In line with the translational potential of metabolic therapy, we will also evaluate its effect in the context of standard heart failure medication (ß-blockers, ACE inhibitors). The results will foster the understanding of maladaptive processes of cardiac hypertrophy during emergence, development and therapy of heart failure at the cellular and molecular level. |
| Project web page: | http://confolab.sav.sk/ovsb/projekty/aktivne-projekty/vega-2-0182-21/ |
VEGA - Untangling the roles of obesity, diet, and diabetes in the development of cardiomyopathy in the female ZDF rat
Rozpoznanie úloh obezity, stravy a cukrovky pri rozvoji kardiomyopatie u samíc ZDF potkana
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | 2/0147/23 |
| Program: | VEGA |
| Project leader: | RNDr. Cagalinec Michal PhD. |
| Annotation: | Cardiovascular diseases (CVDs) are the leading cause of morbidity worldwide. Accumulating evidence indicates that although pre-menopausal women have a lower risk of CVDs, compared to age-matched men, this advantage is lost in diabetic premenopausal women where the leading case of the CVD is the development of diabetic cardiomyopathy (DCM). DCM relates to heart remodeling and functional changes. Few human, as well as rodent studies, including the Zucker Diabetic Fatty (ZDF) rat model, have assessed molecular and cellular mechanisms regarding gender differences of DCM. For male ZDF rats diastolic dysfunction, calcium signaling disturbance, and myocyte hypertrophy has been reported. Therefore, we aim to characterize intracellular calcium dynamics and ultrastructure of cardiomyocytes in female ZDF rats and compare them between the lean and obese models with or without developed DCM to reveal the mechanisms behind diet-, obesity-, and diabetes-induced pathology. |
| Project web page: | http://confolab.sav.sk/ovsb/projekty/aktivne-projekty/vega-2-0147-23/ |
ExoTREAT - Suicide gene therapy mediated by mesenchymal stromal and pancreatic tumor cell-excreted extracellular vesicles in the treatment of pancreatic ductal adenocarcinoma
Samovražedná génová terapia sprostredkovaná exozómami z mezenchýmových stromálnych a pankreatických nádorových buniek v liečbe duktálneho adenokarcinómu pankreasu
| Duration: | 1. 7. 2021 - 30. 6. 2025 |
| Evidence number: | APVV-20-0143 |
| Program: | APVV |
| Project leader: | Mgr. Cihová Marína PhD. |
| Annotation: | Despite the advances in pancreatic cancer research, the survival of pancreatic ductal adenocarcinoma (PDAC) patients remains low. Innovative therapies based on novel principles are therefore urgently needed. Tumor tropic behavior of mesenchymal stromal cells (MSCs) led to the development of prodrug cancer suicide gene therapy. MSCs with integrated suicide gene yeast cytosine deaminase::uracilphosphoribosyl transferase (yCD::UPRT) proved to be an effective tool in the eradication of several deadly cancers in preclinical studies. The attractiveness of this approach lies in eliminating the systemic toxicity of 5-fluorouracil (5-FU) by non-toxic prodrug 5- fluorocytosine (5-FC) administration, which is metabolized into toxic 5-FU intracellularly. We found that yCD::UPRT gene-transduced MSCs release extracellular vesicles that carry mRNA of the suicide gene in their cargo. Their sustained intracellular killing activity and prolonged temperature stability would assign them to “off-the-shelf” medication. The development, characterization, and safety assessment of this innovative vesicle-mediated PDAC- targeted therapy will be the main objective of the proposed project. PDAC cell lines and primary pancreatic tumor cells will be treated with suicide gene vesicles to determine the most efficient approach both in vitro and in vivo. The most relevant preclinical models - patient-derived organoids and xenografts, which closely mimic the patient tumor complexity, will be used for these purposes. Moreover, PDAC cell-released extracellular vesicles, known to form a pre-neoplastic niche, will be studied and characterized. Combining gene therapy with standard of care drugs administered in MSC- and tumor-vesicles will be assessed to prevent metastases formation. We believe that the new opportunities bought by scientific knowledge and multidisciplinary collaboration will help us to achieve the project's goals and potentially improve the survival of patients with PDAC. |
PROSEC - Blood elements-derived secretome as a source of bioactive factors mediating the neuroprotection
Sekretóm krvných elementov v úlohe zdroja bioaktívnych faktorov sprostredkujúcich neuroprotekciu
| Duration: | 1. 7. 2022 - 30. 6. 2026 |
| Evidence number: | APVV-21-0069 |
| Program: | APVV |
| Project leader: | RNDr. Bonová Petra PhD. |
| Annotation: | Stroke is the second leading cause of death and disability worldwide. In ischemic events, treatment options are limited to a single, time-limited, drug intervention (tPA) with the risk of hemorrhagic transformation. In the next decade, a progressive increase of stroke cases is expected, by up to one-third. Moreover, this number may be even higher in the context of the SARS-CoV-2 coronavirus pandemic. The need for additional supportive and regenerative therapies is thus becoming even more topical. In clinical practice, the remote conditioning method (RIC) is increasingly being used to mitigate the effects of stroke. The fundamentals of RIC lie in the endogenous stimulation of the mechanisms leading to neuroprotection via ischemia of a distant organ or limb. Despite many benefits, a serious limiting factor of the therapy is the timing, dose, but also unaffectable factors such as age, sex, and metabolic dysfunction of the patients. Cell therapy also appears to be an effective tool in regenerative medicine. However, due to safety issues, less than 1% of trials have been directed to stroke. In addition to graft cells, the positive effects of transplantation are mainly associated with the microenvironment that the cells produce by secretion. The use of a secretome thus eliminates the risk associated with the transplantation of living and potentially pluripotent cells. Another benefit in cell therapy safety issues is the paracrine activity in most of the differentiated cell types, blood cells including. Our experimental approach is a combination of both of the above strategies - it uses the paracrine activity of blood elements that have been endogenously stimulated by RIC. As a result, the blood cells derivate the secretome having a significant neuroprotective effect in a model of brain ischemia. The next essential step to bring this attractive strategy closer to clinical practice is the detailed characterization of the secretome and its bioactive properties. |
Investigation of the regulatory effect of serotonin on neuroblast migration in the neurogenic region of the adult brain
Skúmanie regulačného účinku sérotonínu na migráciu neuroblastov v neurogénnej oblasti mozgu v dospelosti
| Duration: | 1. 1. 2022 - 31. 12. 2024 |
| Evidence number: | 2/0119/22 |
| Program: | VEGA |
| Project leader: | RNDr. Martončíková Marcela PhD. |
| Annotation: | In the subventricular zone (SVZ) of the lateral ventricles of the mammalian brain, new neurons are generated throughout life. They migrate for a long distance via the rostral migratory stream (RMS) to the olfactory bulb (OB) where they differentiate and integrate to neuronal circuits. Understanding the mechanisms governing the migration is important for the potential use of neural precursors for therapeutic purposes. Neuroblasts in the SVZ-RMS-OB migrate along blood vessels and the migration is regulated by brain-derived neurotrophic factor – BDNF produced by endothelial cells of blood vessels. Recent studies suggest the effect of the neurotransmitter serotonin on the proliferation and migration of neuroblasts in the SVZ-RMS-OB. The aim of our project is to map the localization of serotonin receptors in the SVZ-RMS-OB and to examine the effects of serotonin on neuroblast migration and the possible link between BDNF and serotonin regulatory systems in the regulation of migration in vitro on the SVZ-RMS-OB explant. |
Evaluation of the role of tumor microenvironment stromal component in breast cancer treatment outcome using an organoid model
Sledovanie vplyvu stromálnej zložky nádorového mikroprostredia na liečbu karcinómu prsníka v organoidovom modeli
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0067/22 |
| Program: | VEGA |
| Project leader: | Mgr. Plavá Jana PhD. |
Evaluation of 5G radiation induced genotoxicity and assessment of phytochemicals as modulator of radiation induced DNA damage and cancer
Stanovenie genotoxicity indukovanej 5G žiarením a štúdium fytochemikálií ako modulátorov radiáciou indukovaného poškodenia DNA a rakoviny
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | 2/0082/23 |
| Program: | VEGA |
| Project leader: | Gulati Sachin PhD. |
| Annotation: | There are controversial data available regarding exposure of radiofrequency radiation (RFR) from mobile communication and induction of reactive oxygen species, DNA damage, and cancer. However, the available studies are not directly comparable because they were performed at different parameters of exposure, which were shown to be critical for appearance of the RF effects. We propose evaluation of genotoxic effects of RFR used in 5G signals. Genotoxicity and oxidative stress will be evaluated with appropriate combination of endpoints. Long term exposure of 5G signals in induction of cell malignant transformation will be evaluated using SCID mice. Phytochemicals such as extract from Gingko biloba and curcumin will be assessed in combination with 5G signals and high dose gamma-ray’s radiation used in radiotherapy to check their radio-protective impact of DNA damage, oxidative stress, and cell malignancies. |
Assessment of DNA damage and genetic instability in hospital workers occupationally exposed to low doses of ionizing radiation
Stanovenie poškodenia DNA a genetickej nestability v bunkách rádiológov vystavených nízkym dávkam ionizujúceho žiarenia
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | 2/0012/23 |
| Program: | VEGA |
| Project leader: | Mgr. Košík Pavol PhD. |
| Annotation: | High doses of ionizing radiation (IR) induce DNA damage and genetic instability relevant to various types of tumors. However, the consequences of chronic human exposure to low doses of IR, which are specific for diagnostic medical environment, are not conclusive so far. Our preliminary data suggests an increased DNA damage and genetic instability in Slovak radiology workers. The aim of this project is to validate these preliminary results with expanded group of radiologists (medical workers) by using applying comprehensive panel of state-of-the-art techniques, which would substitute clinically relevant protective measures. We will use the “gold standard” cytogenetic methods enriched with Metafer fluorescence microscopy and FISH. The obtained results will be correlated with cumulative dose of IR and clinical data of radiology workers including overcoming COVID-19 and vaccination. We will estimate a cancer risk in radiologists. We will investigate the persistence and genetic instability after COVID-19 by FISH. |
Stress-induced translocation of the intestinal microbiota in the regulation of the inflammatory response - sex differences in rodents
Stresom indukovaná translokácia črevnej mikrobioty v regulácii zápalovej odpovede - pohlavné rozdiely u hlodavcov
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0160/22 |
| Program: | VEGA |
| Project leader: | Ing. Vargovič Peter PhD. |
| Annotation: | Chronic stress alters communication between neuroendocrine and immune system, what significantly participates in the development of diseases related to chronic inflammation. In this respect, the intestinal microbiota, which affects both of these systems, plays an important role. Stress-related diseases show significant gender differences as a result of nerve, endocrine, immune differences, but also changes in the microbiota. Stress increases the translocation of the intestinal microbiota into the bloodstream, tissues and organs, thereby affecting the activity of immune cells and their inflammatory activity. The aim of the project is to describe the differences between male and female mice in stress-induced translocation of intestinal bacteria and its role in the communication of the neuroendocrine and immune systems, especially in the regulation of the inflammatory response. |
Synthesis, physicochemical, biological properties of glycoconjugates, N-heterocycle-based precursors and polysaccharide derivatives as potential anticancer and antiviral agents
Syntéza, fyzikálno-chemické a biologické vlastnosti prekurzorov na báze glykokonjugátov, N-heterocyklov a derivátov polysacharidov ako potenciálnych antikarcinogénnych a antivirotických liečiv
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0071/22 |
| Program: | VEGA |
| Project leader: | Mgr. Horváthová Eva PhD. |
| Annotation: | The project deals with new synthetic saccharide derivatives (heparin-like polysaccharides and chitosan-like saccharides substituted with imidazoline groups, imino-aromatic derivatives of quinazolinones and their complexes with transition metals). The molecular structure and photochemical properties of new synthesized glycoconjugates and polysaccharides will be analysed by means of NMR spectroscopy, together with HRMS, UV-VIS, FTIR, SEC-MALS and AFM methods, combined with theoretical calculations (DFT; geometry optimization, calculations of NMR parameters). Saccharide derivatives will be prepared by new synthetic methods utilizing catalytic effects of metal ions, microwave radiation and ultrasound. Apart from photochemical properties, antioxidant, cytotoxic, antiproliferative effects and interactions with DNA (cleavage, intercalation) will be tested as well. |
HNOSES - Study of biological effects of H2S/NO/selenium products and molecular mechanisms of their actions
Štúdium biologických účinkov produktov H2S/NO/selénovej interakcie a molekulárne mechanizmy ich pôsobenia
| Duration: | 1. 7. 2020 - 30. 6. 2024 |
| Evidence number: | APVV-19-0154 |
| Program: | APVV |
| Project leader: | RNDr. Ondriaš Karol DrSc. |
| Annotation: | Reactive sulfur (RSS), nitrogen (RNS) and selenium species (RSEs) are groups of simple chemical molecules of radical or non-radical nature, which interact with cellular components and thereby influence various biological processes. The study of biological effects of RSS, RNS and RSeS and their mutual interactions is important for the understanding of their biological roles, moreover for the potential application of these species in medicine. Our studies of the reactive species interaction in the last 3 years showed that: - products of hydrogen sulfide (H2S) and polysulfides (H2Sn, n≥2) interaction with nitric oxide (NO) or selenium compounds (R-Se) significantly affect oxygen radicals concentrations, hydroperoxide cleavage, DNA damage, rat blood pressure and tension/relaxation of isolated aorta. - H2S and H2S2 interact with tetracycline antibiotics, mainly doxycycline (DOXY) and thereby produce/inhibit superoxide and hydroxyl radicals and induce/inhibit DNA damage These findings imply the possibility that reactive oxygen species (ROS) and other H2S/NO/R-Se interaction products affect (patho)physiological functions in living organisms. In the project´s aims we will build on the previous findings and investigate following new hypotheses: 1) Do mixtures (H2Sn/R-Se, H2Sn/R-Se/NO alebo H2Sn/DOXY) produce ROS or other biologically active compounds? 2) Are these products responsible for production/inhibition of radicals, cleavage of hydroperoxides and induction/inhibition of DNA damage? 3) Do interaction products affect ferroptosis or intracellular calcium concentration in cells? 4) Do these products affect rat blood pressure, arterial pulse waveform and tension of isolated arteries? The aim of this project is to investigate the chemical biology, activity and effects of the interaction products on cellular, organ and whole-organism level. These findings may contribute to the development of novel therapeutic interventions based on the modulation of cellular redox biology. |
Study of genotoxic effects from magnetic resonance imaging in human lymphocytes
Štúdium genotoxických zmien indukovaných magnetickou rezonanciou v ľudských lymfocytoch
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | 2/0140/23 |
| Program: | VEGA |
| Project leader: | RNDr. Zastko Lucián PhD. |
| Annotation: | Magnetic resonance imaging (MRI) has become an integral noninvasive diagnostic imaging tool. By using a static and a time-varying gradient magnetic field in combination with a radiofrequency field, MRI provides excellent tissue contrast. Recent reports on potential genotoxic effects induced by routine 1.5 T cardiac MRI examination in lymphocytes have raised safety concerns. However, genomic instability caused by MRI scan has been examined using only few techniques so far and relationship of the obtained to situation when cells are exposed in human body is also questionable. The aim of our study is to reveal whether standardized MRI of 1.5 T is able to induce genotoxicity - using the gamma H2AX/53BP1 DNA repair foci, comet assay, micronuclei analysis, chromosomal aberration, apoptosis, and ROS induction in human lymphocytes in vitro, situated in tissue equivalent phantom of human body during procedure. Identifying genotoxic effects of MRI can result in possibility to some extent adjust its diagnostic use. |
aaa - Study of genetic instability in cells from leukemic patients and chemotherapy-resistant preleukemic stem cells at remission for prevention of relapses
Štúdium génovej nestability v bunkách leukemických pacientov a chemoterapeuticky-rezistentných preleukemických kmenových buniek pocas remisie ako prevencia relapsu
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0138/22 |
| Program: | VEGA |
| Project leader: | Mgr. Jakl Lukáš PhD. |
| Annotation: | Leukemia is the most prevalent malignity in children. It is known that some chromosomal translocations resulting in preleukemic fusion genes (PFG) in hematopoietic stem/progenitor cells (HSPC) are associated with leukemia. Translocation occurs as a result of incorrect DNA repair of DNA double-strand breaks (DSB). Results of our previous study show that there is possible correlation between presence of PFG and increased level of endogenous DSB assessed with gH2AX/53BP1 DNA repair foci. Our first aim is to reveal whether the patients with most frequent PFG has higher level of DNA repair foci. It is considered that some preleukemic cells, which survive chemotherapy, could be a source for relapse. Our second aim is to characterize subpopulations of HSPC for presence of PFG in leukemia patients after chemotherapy in remission. Identifying of subpopulation of preleukemic stem cells responsible for relapse is needed for potential immunotherapy to prevent relapses. |
GlycoOFFviro - The study of HCMV virokine interactions underlying regulation of the immunological synapse for the development of a novel immunotherapeutic concept based on viral tricks
Štúdium interakcií HCMV virokínov zapojených do imunologickej synapsy pre vývoj nového imunoterapeutického konceptu založeného na vírusových trikoch.
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | VEGA 02/0026/22 |
| Program: | VEGA |
| Project leader: | Mgr. Nemčovičová Ivana PhD. |
| Annotation: | The molecular interactions regulating immune response take place in a nanoscale gap between T cells and antigen presenting cells, termed the immunological synapse. If these interactions are dysregulated, the host is susceptible to pathogens or tumor escape at one extreme and autoimmunity at the other. Treatments targeting the synapse have helped to establish immunotherapy as a mainstream element in cancer treatment. The novelty of our concept is to look at the molecules of immunological synapse that cytomegalovirus uses to turn down the immune system to figure out how to develop a new biotherapeutic drug. Within the project, we will investigate several HCMV virokines that function on NK and T cells and how they act in healthy and diseased 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. This project is the logical continuation of our long-term joint initiative. |
PANDIAREG - Investigating the role of GPR180/CTHRC1 signalling in regulation of pancreatic B cell function and pathogenesis of diabetes
Štúdium úlohy GPR180/CTHRC1 signalizácie v regulácii funkcie β buniek pankreasu a patogenéze diabetu
| Duration: | 1. 9. 2022 - 31. 8. 2025 |
| Evidence number: | 1260/02/02 |
| Program: | SASPRO |
| Project leader: | Mgr. Balážová Lucia PhD. |
GAMS - Effects of GLP-1 Analog on Multiple Sclerosis
Účinky GLP-1 analógu na sclerosis multiplex
| Duration: | 1. 7. 2022 - 30. 6. 2026 |
| Evidence number: | APVV-21-0261 |
| Program: | APVV |
| Project leader: | doc. MUDr. Imrich Richard DrSc. |
| Annotation: | The primary objectives of our study are evaluating effects of GLP-1 agonist treatment on axonal damage and neurodegeneration. Annualized changes in brain/grey matter volumes and plasma levels of neurofilament L will serve as the primary variables. The secondary objectives are to explore effects of GLP-1 agonist treatment on insulin resistance and cognitive functions in MS. Insulin resistance will be evaluated using indices of insulin sensitivity based on oral glucose tolerance test, and cognitive functions will be tested using Symbol Digit Modalities (SDMT) and Stroop test. Several others exploratory analyses and functional tests including non-invasive evaluation of endothelial dysfunction will be also performed in the study. Currently, there is a substantial gap in knowledge of clinically relevant GLP-1 analog effects on the MS progression. Despite some progress in development of novel treatments for relapsing MS in recent years, many unmet needs remain in terms of therapeutics and disability avoidance. If successful, our results may provide basis for a potential therapy with GLP-1 analogs for the treatment of patients with MS with aim at slowing the process of neurodegeneration and prevent or delay the development of co-morbidities associated with insulin resistance (mainly cardiovascular diseases and type 2 diabetes). |
Effects of regular exercise training on molecular, cellular and whole body processes associated with ageing: : Multi-organ integrative approach
Účinky pravidelného cvičenia na bunkové a molekulárne procesy asociované so starnutím: multi-orgánový integratívny prístup.
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0076/22 |
| Program: | VEGA |
| Project leader: | prof. MUDr. Ukropcová Barbara PhD. |
Effect of electrical stimulation on regeneration of injured neural pathways.
Účinok elektrickej stimulácie na regeneráciu poškodených nervových dráh.
| Duration: | 1. 1. 2020 - 31. 12. 2023 |
| Evidence number: | VEGA 2/0098/20 |
| Program: | VEGA |
| Project leader: | RNDr. Gálik Ján CSc. |
| Annotation: | Despite intensive efforts of researchers and clinicians, there is no, so far, an effective therapy for the recovery of nervous tissue after ischemic or traumatic injury. None of the few clinically approved procedures leads to satisfactory results. The aim of proposed project is to increase the effectiveness of current therapies by combining them with sustained electrical stimulation of injured tissue, which can facilitate regeneration of axons and provide guidance for their growth. We will test the possible synergistic effect of sustained stimulation with surgical, pharmacological and physical interventions. |
The emerging role of the microbiome in hematologic cancer patients receiving high-dose chemotherapy with hematopoietic stem cell transplantation.
Úloha mikrobiómu u hematoonkologických pacientov podstupujúcich vysokodávkovanú chemoterapiu s transplantáciou krvotvorných kmeňových buniek.
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0069/22 |
| Program: | VEGA |
| Project leader: | RNDr. Čierniková Soňa PhD. |
| Annotation: | Targeting the microbiome in cancer treatment faces mounting research interest. Hematopoietic stem cell transplantation (HSCT) became a routine treatment for a wide variety of hematologic malignancies. To eradicate cancer cells, high-dose chemotherapy or radiotherapy is given to the patients as a part of conditioning regimen prior to HSCT. Both treatment modalities lead to mucosal barrier disruption and heavily destroy intestinal biodiversity, followed by severe treatment-associated complications. The aim of the proposed study is to characterize the bi-directional impact of the human gut microbiome and influencing factors on the clinical outcome of patients receiving high-dose chemotherapy with HSCT, mainly in patients with autologous HSCT. Correlation between microbial community structure, metabolic and immunologic pathways and clinical outcome may identify the microbial biomarkers for the early detection of patients at high risk of severe treatment toxicity and post-transplant complications. |
The role of mitochondria in progression of colorectal cancer
Úloha mitochondrií v progresii kolorektálneho karcinómu
| Duration: | 1. 1. 2021 - 31. 12. 2024 |
| Evidence number: | 2/0185/21 |
| Program: | VEGA |
| Project leader: | RNDr. Tyčiaková Silvia PhD. |
| Annotation: | Mitochondria respond to energetic needs and stress stimuli by adapting their structure and function. Their morphology is changed in process of fusion and fission. Tumor cells maintain reprogrammed energetic metabolism towards aerobic glycolysis, display smaller mitochondria and activated dynamin-related protein 1, responsible for mitochondrial fission. Bioenergetic function of mitochondria is usually supressed in tumors. Our preliminary study shown that pro-apoptotic effect of drugs includes enhanced mitochondrial fission in colorectal cancer (CRC) cells. We suppose that mitochondrial morphology and size, changed by fusion and fission affects progression and invasivity of tumor cells. Therefore, we aim to study correlation among mitochondrial fission, status and aggressive phenotype of CRC-derived cells. We will examine the effect of Drp1 knockdown on mitochondria as well as the effect of overexpression of proteins responsible for mitochondrial fusion MFN1/2 in CRC cells in comparison to healthy cells. |
Role of modulation of enzymes endogenously producing H2S in tumor cells
Úloha modulácie endogénnych enzýmov produkujúcich H2S v nádorových bunkách
| Duration: | 1. 1. 2022 - 31. 12. 2024 |
| Evidence number: | 2/0047/22 |
| Program: | VEGA |
| Project leader: | Mgr. Lišková Veronika PhD. |
| Annotation: | Hydrogen sulfide (H2S) is a gaseous transmitter that modulates huge number of physiological and metabolic processes in the cell. In mammals, its intracellular production is ensured by enzymes cystathionine-ß-synthase (CBS), cystathionine-y-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (MPST). Their expression varies significantly between individual types of tumors and affects growth of tumor cells differently, which may influence levels of endogenous H2S. Aim of this project is to determine the role of these enzymes in colorectal and ovarian cancer cells by knockout of genes encoding the enzymes which are responsible for production of endogenous H2S. We hypothesize that this intervention could significantly affect properties of tumor cells such as proliferation, migration and could alter their susceptibility to apoptosis. Knockout of any of monitored genes will have an effect on the growth inhibition of the studied cells, could help to find a more effective tool in the fight against tumor cell growth. |
DRPGE - The role of DNA repair proteins in gene repression
Úloha proteínov DNA opravy v génovej represii
| Duration: | 1. 7. 2022 - 30. 6. 2026 |
| Evidence number: | APVV-21-0210 |
| Program: | APVV |
| Project leader: | Ing. Čipáková Ingrid PhD. |
LEBRE - Multidrug resistance of leukemia cells - Phenotype caused by interference of multimodal molecular reasons
Viaclieková rezistencia u leukemických buniek - fenotyp spôsobený interferenciou viacerých molekulárnych príčin
| Duration: | 1. 7. 2020 - 30. 5. 2024 |
| Evidence number: | APVV-19-0093 |
| Program: | APVV |
| Project leader: | Ing. Brtko Július DrSc. |
Effects of natural polyphenol and nonsteroidal anti-inflammatory drug combination therapy on the tumor microenvironment
Vplyv kombinovanej terapie prírodnými polyfenolmi a nesteroidnými protizápalovými liečivami na nádorové mikroprostredie
| Duration: | 1. 1. 2021 - 31. 12. 2024 |
| Evidence number: | 2/0061/21 |
| Program: | VEGA |
| Project leader: | RNDr. Grossmannová Katarína PhD. |
Effect of combinaion therapy with carnosine on tumorigenesis in colorectal carcinoma models
Vplyv kombinovanej terapie s karnozínom na proces tumorigenézy v modeloch kolorektálneho karcinómu
| Duration: | 1. 1. 2020 - 31. 12. 2023 |
| Evidence number: | 2/0090/20 |
| Program: | VEGA |
| Project leader: | RNDr. Baráthová Monika PhD. |
| Annotation: | Continuous search for new approaches and treatment strategies is essential in the treatment of cancer. Multiple drug combination therapy simultaneously involves several cellular mechanisms in order to make treatment more effective, reduce toxicity and prolong patient life. New therapeutic approaches use not only the combination of anticancer drugs but also natural substances. By ccombination therapy with carnosine and chemotherapeutic agents we want to affect mitochondrial mechanisms - bioenergetics, quenching of active forms of oxygen, indirectly also stability of HIF1a subunit, and use the impact of carnosine on pH regulation in tumor cells expressing CA IX. Together with chemotherapeutics, we want to analyze the impact of such combinations on proliferation, migration, metastatic potential as well as on the chemotherapy-resistant cancer stem cell pathways. The aim of the project is also to use 3D models of cell cultivation in spheroids and to introduce a method of forming microtumors from clinical samples. |
The effect of neuropeptides involved in food intake regulation on neuritogenesis and synaptogenesis
Vplyv neuropeptidov súvisiacich s príjmom potravy na neuritogenézu a synaptogenézu
| Duration: | 1. 1. 2021 - 31. 12. 2023 |
| Evidence number: | 2/0148/21 |
| Program: | VEGA |
| Project leader: | Mgr. Bačová Zuzana PhD. |
Influence of NS1 protein and influenza virus load on the pathogenesis and innate immune response in brains, hearts and spleens of infected mice
Vplyv proteínu NS1 a infekčnej dávky vírusu chrípky na patogenitu a vrodenú imunitnú odpoveď v mozgoch, srdciach a slezinách infikovaných myší
| Duration: | 1. 1. 2020 - 31. 12. 2023 |
| Evidence number: | 2/0031/20 |
| Program: | VEGA |
| Project leader: | doc. RNDr. Betáková Tatiana DrSc. |
| Annotation: | Despite the widespread application of vaccination programs, influenza viruses are still among the most harmful human pathogens. Influenza encephalopathies, encephalitis lethargica and Reye´s syndrome are rare, but serious diseases that manifest with influenza infection. High pathogenic strains are able to spread to the brain, liver and other organs. NS1 protein counteracts the induction of antiviral response. Our preliminary data shows, that the immune response was activated in the brain and spleen of mice infected with low pathogenic influenza virus despite of fact that virus was not detected in these organs. The main aim of this project is to investigate the influence of virus pathogenicity as well as NS1 protein on the spread of the virus into the brain, heart and spleen of infected mice and on their ability induce RIG-1-like receptor signaling pathway in these organs. We also suggest that the cells of immune system like macrophages, neutrophils, etc. play more important role in pathogenesis. |
Innate antiviral defense responses of selected human skin cells to tick-borne encephalitis virus and their modulation by bioactive substances in tick saliva
Vrodené antivírusové obranné reakcie vybraných buniek ľudskej kože voči vírusu kliešťovej encefalitídy a ich modulácia bioaktívnymi látkami v slinách kliešťov.
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0108/22 |
| Program: | VEGA |
| Project leader: | Mgr. Štibrániová Iveta PhD. |
| Annotation: | Ticks and tick-borne viruses (TBVs) are an extraordinary medical problem. Together with the host, they form an interactive triangle in which the skin of the host is the place of their first contact. Despite an effective barrier function, the skin is still the main gateway for most tick-borne pathogens (including viruses) to enter, allowing them to multiply and disseminate extensively to other organs. The transmission of viruses through tick bites is not a mechanical process but is supported by tick saliva. Skin cells, including keratinocytes, are able to detect and defend against viruses also thanks to the mechanisms of innate antiviral protection. Defining an environment at the tick-host interface that is unfavorable for TBVs could open up the possibility of creating a new universal vaccine against TBVs. |
SYNDEAF - Identification of novel genetic variants in syndromic hearing loss by whole exome sequencing
Vyhľadávanie nových génových variantov syndrómových porúch sluchu pomocou celoexómového sekvenovania
| Duration: | 1. 7. 2021 - 30. 6. 2025 |
| Evidence number: | APVV-20-0236 |
| Program: | APVV |
| Project leader: | RNDr. Gašperíková Daniela DrSc. |
RICTRANSPROT - Investigation of the Host – Parasite, Cell - Rickettsia Relationship, Monitored by Transcriptomic and Proteome Studies.
Výskum hostiteľsko – parazitických, bunkovo - Rickettsiových vzťahov, monitorovaných pomocou transcriptomických a proteomických štúdií.
| Duration: | 1. 7. 2020 - 30. 6. 2024 |
| Evidence number: | APVV-19-0066 |
| Program: | APVV |
| Project leader: | RNDr. Sekeyová Zuzana PhD. |
| Annotation: | In recent years, the host – parasite relationship is increasingly monitored by transcriptomic and proteome studies. It is obvious, that host–pathogen interactions involves protein expression changes in both actors the host cells and the rickettsial pathogen. An understanding of the nature of these interactions at the proteomic level will provide insight into metabolic processes, critical regulatory events of the host cells as well as the mechanism of pathogenesis of rickettsioses. We aim to study these regulatory events, control mechanisms, which underlie not only the functioning of individual cells but also the processes of differentiation and development, protein synthesis, processing, folding or degradation, both in infected cells and Rickettsiae. We will use premium, the state-of-the-art proteomic technologies enabling of measuring several thousands of proteins within a few hours, they will permit us to significantly increase the analytical depth as well as coverage in complex proteome analyses. We will be interested in the function of proteins with respect to the course of protein expression at which can be regulated the flow of information from the genome to the Proteome, in both Rickettsiae and the infected cells. We aim to search for transcriptional changes in infected cells observed following exposure to Rickettsiae and to a nutrient stress that will be verified, starting from amplified cDNA and total RNA as templates, means we will apply an approach that has great potential for the study of mechanisms behind the virulence and intracellular survival of members of the genus Rickettsia. |
| Project web page: | https://portal.apvv.sk/index.aspx?Module=Application&Page=Project&MenuID=287&ProjectID=19604 |
Research of clinical and genetic aspects of ketotic hypoglycemia in children
Výskum klinických a genetických aspektov ketotických hypoglykémií u detí
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 1/0659/22 |
| Program: | VEGA |
| Project leader: | RNDr. Gašperíková Daniela DrSc. |
imunocheck - Harnessing the immunological mechanisms in various subtypes of B cell lymphoma
Využitie imunologických mechanizmov v rôznych subtypoch B-bunkových lymfómov
| Duration: | 1. 7. 2020 - 30. 6. 2024 |
| Evidence number: | APVV-19-0212 |
| Program: | APVV |
| Project leader: | RNDr. Cholujová Dana PhD. |
| Annotation: | Malignant lymphomas are mostly incurable blood cancers affecting different white blood cells formed in lymphoid structures, including the lymph nodes, spleen, and bone marrow. They have different origin in B cell development with different biological properties and clinical aggressiveness. This tumor cells compete for space to grow within tumor microenvironment by affecting the surrounding healthy cells in the bone marrow to suppress patient immunity. The purpose of this proposal is to better understand tumor and tumor-driven immune changes and evaluate their phenotypic differences and functional complexity by comprehensive state-of-art technology mass cytometry (CyTOF). Furthermore, we will study the immunological mechanisms “immune checkpoints” that can be targeted in malignant lymphoma. The better understanding of pathogenesis of B-cell malignancies will lead to new therapeutic strategies directed against tumor and immune cells to completely eradicate tumor in individual patient. |
Use of microfluidic systems for risk assessment of xenobiotics
Využitie mikrofluidných systémov na hodnotenie rizika xenobiotík
| Duration: | 1. 1. 2021 - 31. 12. 2024 |
| Evidence number: | 2/0121/21 |
| Program: | VEGA |
| Project leader: | RNDr. Šramková Monika PhD. |
| Annotation: | Microfluidic systems coupled with different cell types offer an alternative platform for the risk assesment of different xenobiotics in order to simulate physiological conditions, improve testing, and reduce the animal use. Liver and kidney cells play a key role in the detoxification and elimination of xenobiotics and their metabolites, and represent two primary targets of the toxic effect of xenobiotics. In the present project we will use various in vitro conditions (monolayer, 3D spheroids, Transwell inserts) to evaluate the biological effect of selected xenobiotics (aflatoxin B1, ifosfamide) and gold nanoparticles, including an advanced in vitro system (IVTech), which will enable liver-kidney co-cultivation in a bioreactor to better simulate in vivo conditions. By combining biological, molecular methods, as well as imaging techniques and analytical tests, we gain new valuable knowledge about the interaction of individual tissues, the metabolism of xenobiotics and their effect on the relevant tissue. |
Nanomedical approach to fight pancreatic cancer via targeting tumor-associated carbonic anhydrase IX
Využitie nanomedicíny v boji proti rakovine pankreasu prostredníctvom zacielenia nádorovo- asociovanej karbonickej anhydrázy IX
| Duration: | 1. 7. 2021 - 30. 6. 2025 |
| Evidence number: | APVV-20-0485 |
| Program: | APVV |
| Project leader: | RNDr. Csáderová Lucia PhD. |
BIOTREAT - Development of bioimmunotherapeutics inspired by viral tricks: TREATing despite the TRICKs
Vývoj bioimunoterapeutík inšpirovaný vírusovými trikmi: Liečenie aj napriek trikom
| Duration: | 1. 7. 2020 - 30. 6. 2024 |
| Evidence number: | APVV-19-0376 |
| 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. |
Development of patients derived xenografts models and their utilization for personalized treatment of uveal melanoma
Vývoj modelov xenotransplantátov z pacientských tkanív a ich využitie na personalizáciu liečby malígneho melanómu uvey
| Duration: | 1. 1. 2021 - 31. 12. 2024 |
| Evidence number: | 1/0395/21 |
| Program: | VEGA |
| Project leader: | Ing. Demková Lucia PhD. |
| Annotation: | Uveal melanoma (UM) is the most common intraocular malignant tumor in adults, metastasizing in 50% of patients. Despite reliable prognostic markers, this malignancy is associated with a high mortality rate due to tumor cell resistance. Treatment development is limited by the poor availability of appropriate preclinical models. Among the most valuable are those derived from patients' tumors, so-called patient-derived xenografts (PDX), on the development of which the presented project will focus. In UM pathogenesis crucial role plays epigenetic deregulation. Due to their reversible nature epigenetic inhibitors are in the spotlight of current clinical research. We hypothesize that they can sensitize resistant UM cells and, therefore, might considerably improve the therapeutic index of signaling pathways inhibitors. PDX models will be applied to test the most effective drug combinations. They will allow the use of a personalized approach for adjuvant therapy development to prevent metastasis in high-risk patients. |
Development of a lateral flow assay for the diagnosis of zoonotic disease: Q fever.
Vývoj testu na báze laterVývoj testu na báze laterálneho toku (“lateral flow assay) na diagnostiku zoonotického ochorenia: Q horúčka
| Duration: | 1. 1. 2021 - 31. 12. 2024 |
| Evidence number: | 2/0023/21 |
| Program: | VEGA |
| Project leader: | Mgr. Flores-Ramírez Gabriela PhD. |
- The development of translationally relevant regenerative and reparative strategies after spinal cord trauma
Vývoj translačne relevantných regeneračných a reparatívnych stratégií po traumatickom poranení miechy
| Duration: | 1. 7. 2020 - 30. 6. 2024 |
| Evidence number: | APVV-19-0324 |
| Program: | APVV |
| Project leader: | RNDr. Lukáčová Nadežda DrSc. |
| Annotation: | The aim of this project is to investigate the regulatory impact of clinically approved/tested anti-inflammatory drugs on the polarization of M1/M2 macrophages, which play a key role in activation of pro-regenerative molecules following traumatic spinal cord injury and design translational strategies that have the potential to improve functional recovery of experimental animals. We propose to examine the protein profile of selected spinal cord regions (lesion site, above and below the site of injury) after Th9 compression and application of methylprednisolone, atorvastatin, siponimod and VX-210 in acute/subacute phase of spinal injury, and evaluate their neuroprotective potential. We intend to develop a new technology that allows local application of the most effective drug with a gradual, time-dependent release to the site of spinal cord lesion. We suggest, that drug with the most efficient anti-inflammatory and antioxidant effect in combination with VX-210 (an inhibitor of Rho activity) locally administered via magnetic nanoparticles, will make the spinal treatment more effective and support the regenerative potential of nerve tissue. We plan to stimulate the functional recovery of motor and sensory functions by physical rehabilitation and long-term application of a weak electric field at the lesion site. The neuroprotective effect of synergic action of proposed approaches will be evaluated by analyzes of the expression of pro-regenerative signal molecules, axonal outgrowth, inter-neuronal and neuromuscular junctions and functional recovery. |
DITIMA - Development of unique TiMg composite dental implant
Vývoj unikátneho TiMg kompozitného zubného implantátu
| Duration: | 1. 7. 2021 - 30. 6. 2025 |
| Evidence number: | APVV-20-0417 |
| Program: | APVV |
| Project leader: | RNDr. Takáčová Martina PhD. |
| Annotation: | Dental implants (Dis) become more affordable and sought solution across a globe, the will be in a place for longer periods and a need for maintenance will decrease. Titanium (Ti) and Ti alloys are the most widely utilized materials for production of DI. Even though Ti-based DI are used with a high success rate, two major issues have remained insufficiently resolved: the stress-shielding effect and their insufficient surface bioactivity. That pushes competition, progress and R&D in the related area further and brings a need for novel solutions, approaches and material concepts. The main aim of proposed project is a development of an innovative endosseous biomedical DI fabricated from the unique partially biodegradable Ti - magnesium (Mg) composite material. New DI will minimize the main drawbacks of the contemporary DI, while it maintains the mechanical performance and fatigue endurance of Ti-based references. An advantageous combination of the mechanical, fatigue, corrosion and biological properties of developed DI is owing to a special DI`s design, which reflects and takes advantage of Ti17Mg, the material it will be manufactured from. Ti17Mg is the experimental powder metallurgy material invented by project partners, which selectively exploits the advantages of both biometals. In the project a new DI will be designed and optimized, in order to reflect unique behavior and workability of Ti17Mg. Performance of DI will be assessed and optimized systematically in an environment, which simulates real-life conditions in a human body, including mechanical, fatigue and corrosion testing, and in-vitro and in-vivo biological evaluation using cell culture, small and large animal models. All assays will be carried out in accordance with related ISO specifications. It is anticipated that at the end of the project new innovative high value-added DI is available and pending for testing in a human body. Expectedly TRL 6 will be accomplished at the end of project. |
The importance of interaction products of H2S with S-nitrosoglutathione/selenium derivatives in the regulation of cardiovascular hemodynamics and cardiac mitochondrial functions
Význam produktov interakcie H2S s S-nitrózoglutatiónom/selénovými derivátmi v regulácii srdcovocievnej hemodynamiky a funkcií srdcových mitochondrií
| Duration: | 1. 1. 2021 - 31. 12. 2024 |
| Evidence number: | VEGA/2/0091/21 |
| Program: | VEGA |
| Project leader: | Mgr. Mišák Anton PhD. |
| Annotation: | It is presumed that the cross-talk between H2S- and NO-mediated signaling pathways can play a role in the regulation of cardiovascular system (CVS). Furthermore, the interaction of H2S with selenium derivatives leads to the formation of new reactive (intermediate) products having a broad biological activity. The aim of this project is to extend results in this field by research on the hemodynamic effects of H2S and NO donors/selenium derivatives interaction products also in the context of cardiac mitochondrial functions. We will study the effect of these products on 35 hemodynamic parameters of normo/hypertensive rats and investigate the association of these effects with energy metabolism, specifically with mitochondrial bioenergetics and the functions of mitoKATP channels. These results may contribute to the understanding of the molecular mechanism of these interactions in the CVS, but they may also build a basis for applied studies leading to the use of the interaction products in medical practice. |
Remote conditioning as a prevention and treatment of cerebral ischemia associated with hyper-inflammatory reaction (simulation of COVID-19)
Vzdialené kondicionovanie ako prevencia a liečba ischémie mozgu spojenej s hyper-zápalovou reakciou (simulácia COVID-19)
| Duration: | 1. 1. 2022 - 31. 12. 2024 |
| Evidence number: | 2/0096/22 |
| Program: | VEGA |
| Project leader: | RNDr. Končeková Jana PhD. |
| Annotation: | With the uprise of the virus SARS-CoV-2 pandemic, statistical prognoses for cerebrovascular disease are changing worldwide for the next decades. In more than a third of patients with COVID-19 neurological symptoms occurs in addition to respiratory problems. Infection-induced rapid release of pro-inflammatory cytokines and abnormal levels of coagulation factors in positive patients spikes the likelihood of thrombus formation and a risk of an acute stroke. It is reported, that at least 6% of COVID-19 positive patients have been diagnosed with a stroke, which appears to be an alarming number with the increase of infection incidence. However, the only one FDA accepted medical treatment in a clinic (tPA) has many limitations. Therefore, the increased demand for developing novel non-pharmacological therapies to elevate the tolerance to ischemia has been paying attention. Remote conditioning meets these conditions because of the ability to stimulate the endogenous protective mechanisms ensuring resistance to stroke. |
Involvement of CRH system components in the development of post-traumatic stress disorder
Zapojenie komponentov CRH systému do rozvoja post-traumatickej stresovej poruchy
| Duration: | 1. 1. 2022 - 31. 12. 2024 |
| Evidence number: | 2/0010/22 |
| Program: | VEGA |
| Project leader: | Ing. Tillinger Andrej PhD. |
| Annotation: | Post-traumatic stress disorder (PTSD) is a mental disorder arising from traumatic events that are pathologically manifested by the induction of the fear, hopelessness and scare. The first step in treatment is standard psychotherapy followed by pharmacotherapy (antidepressants/antipsychotics). The neurobiological mechanisms underlying this disease are not well known, but it is thought that pathologically altered functions of several central neurotransmitter and neuropeptide systems may be involved in the etiology of PTSD. The main goal of the project is to determine whether the modulation of the central "stress" CRH system affects the manifestations of the post-traumatic stress response in the animal model of PTSD, i.e. Single prolonged stress (SPS). We will observe how activation of the CRHR2 pathway by a specific agonist or administration of an antipsychotic (aripiprazole) will affect behavior and molecular biological parameters of the CRH system in selected brain regions of SPS exposed animals. |
AMETHYST - Ameliorating Effects of Aging by Physical Exercise: Molecular, Metabolic and Structural Adaptations, Multi-Organ Integrative Approach
Zlepšenie prejavov starnutia pravidelným cvičením: multi-orgánový integratívny prístup k molekulovej, metabolickej a štrukturálnej adaptácii na cvičenie
| Duration: | 1. 7. 2021 - 30. 6. 2025 |
| Evidence number: | APVV-20-0466 |
| Program: | APVV |
| Project leader: | prof. MUDr. Ukropcová Barbara PhD. |
Hepatic, lipid and cardiometabolic parameters changes in obese patients
Zmeny hepatálnych, lipidových a kardiometabolických parametrov u pacientov s obezitou
| Duration: | 1. 1. 2020 - 31. 12. 2023 |
| Evidence number: | 2/0129/20 |
| Program: | VEGA |
| Project leader: | doc. MUDr. Penesová Adela PhD. |
| Annotation: | Morbid obesity (MO, BMI >40 kg/m2) represents 2-3 times higher risk of diabetes, dyslipidemia, cardiovascular (CVS) diseases and non-alcoholic fatty liver disease (NAFLD). Our hypothesis is that even 10% reduction of body weight in MO will lead to improvement of liver parameters, hepatokines, LDL and HDL subfraction of lipoproteins, insulin sensitivity as well as to decrease of CVS risk. The aim of our study is to monitor the effect of intensive life style changes in MO patients and super morbid obesity (SO, BMI >50 kg/m2) on aforementioned parameters during 12 months. We have more than 270 obese, 23 MO and 28 SO patients in our registry. Intervention of life style will be individualized; dominant will be either physical activity and/or diet. Evaluation of hepatokines and lipid subfractions and analysis of anthropometry changes will contribute to understanding and extending the knowledge about the possibilities how to reverse the onset of NAFLD and KVS risk factors in MO and SO patients. |
Coping with psychosocial stress situations in patients with depressive disorder in relation to age and unravelling the mechanisms involved
Zvládanie psychosociálnych stresových situácií u pacientov s depresívnou poruchou v závislosti od veku a odkrývanie zúčastnených mechanizmov
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | 1/0644/23 |
| Program: | VEGA |
| Project leader: | prof. PharmDr. Ježová Daniela DrSc. |
| Annotation: | The main goal of the project is to reveal differences in neuroendocrine changes important for coping with stressors between adolescent and adult patients with depressive disorder compared to healthy subjects. The focus will be given to the disclosure of neurobiological basis underlying consequences of social pain and cognitive deficit on the development and course of depression. Another important goal is to uncover novel endocrine and immune correlates and changes in brain plasticity related to depression. Expected results are likely to help to identify potential therapeutic targets and enable adequate therapeutic intervention with respect to the age of the patient. The project is of a translational nature with an overlap between clinical and preclinical research. The original findings to be obtained will certainly broaden the current knowledge of the pathophysiology of depression and stress coping. They will contribute to better preventive and treatment options for depressive disorders in relation to age. |
Enhancement of endocannabinoid signaling as a promising target for the treatment of stress-related psychiatric disorders
Zvýšenie endokanabinoidnej signalizácie ako perspektívny terč pre liečbu psychických porúch podmienených stresom
| Duration: | 1. 1. 2022 - 31. 12. 2025 |
| Evidence number: | 2/0158/22 |
| Program: | VEGA |
| Project leader: | RNDr. Hlaváčová Nataša PhD. |
Projects total: 126