The list of national projects SAS

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Institute: Biomedical Research Center SAS

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

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

Detection and Characterization of Rickettsiae and Similar Microorganisms.
Detekcia a charakterizácia Rickettsií a im podobných mikroorganizmov
Program: Bilateral - other
Project leader: RNDr. Sekeyová Zuzana PhD.
Annotation:Aims and results shared in this project will provide a number of theoretical knowledge in the field of molecular analysis of rickettsiae and a like microorganisms, with similar direct intrusions into medical practice, means such interferences that will predict and affect an analytical accuracy of diagnoses of rickettsioses, and similar, biologically active intracellular bacteria. We will provide a specific picture of the course of the diseases caused by them, and will try to transfer this knowledge to determination of the specific laboratory indicators of studied pathogens at the molecular level. Reliable diagnoses, vigilance, preparedness, and the availability of efficacious vaccines and antibiotics are dependent on assignation of precise biomarkers that will enhance diagnostic capabilities and reduce delayed identification or misdiagnosis of infectious agent.
Duration: 1.1.2018 - 31.12.2019

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

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

European virus archive goes global.
Európsky vírusový archív sa stáva globálnym.
Program: Horizon 2020
Project leader: RNDr. Klempa Boris DrSc.
Duration: 1.4.2015 - 31.3.2019

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Developing of innovative method of spinal cord injury effective treatment.
Vývoj inovatívnej metódy na efektívnu liečbu poškodenia miechy.
Program: Inter-academic agreement
Project leader: RNDr. Gálik Ján CSc.
Duration: 1.1.2017 - 31.12.2019

Relationship between changes of oxytocin levels and brain development
Vzťah medzi zmenami hladín oxytocínu a vývinom mozgu
Program: Inter-academic agreement
Project leader: RNDr. Bakoš Ján PhD.
Duration: 1.1.2016 - 31.12.2018

The total number of projects: 24