The list of national projects SAS

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Institute: Biomedical Research Center SAS

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

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

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 - 31.12.2020

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

Multiple myeloma intra-clonal heterogeneity: evolution and implications of targeted therapy
Intraklonálna heterogenita v mnohopočetnom myelóme: evolúcia a implikácie pre cielenú liečbu
Program: ERANET
Project leader: RNDr. Jakubíková Jana PhD.
Annotation:The overall objective of this proposal is to investigate evolution of intra-clonal heterogeneity during the development and progression of MM by combining cellular, molecular, and genetic approaches. Moreover, defining the impact of chemotherapy and/or immunotherapy on intra-clonal selection, together with the role of the tumor microenvironment on clonal dynamics on the level of genetic and cellular complexity, will provide the framework for development of novel personalized diagnostic criteria that will lead to more effective therapeutic strategies. Our emphasize will focus on the process of clonal evolution during the development of MM: from premalignant precursor conditions known as MGUS and smoldering MM without clinical manifestations of diseases but with present cytogenetic and/or gene-expression abnormalities to active disease stages. Moreover, we will evaluate the impact of novel chemotherapy/immunotherapy on the dynamic nature of the clonal selection in MM in our ongoing clinical trials, either alone or together with other conventional anti-MM therapies, delineating their ability to prevent recurrence of subclones and resistance to therapy. Furthermore, the role of the tumor microenvironment by characterizing the impact of overall host immunity on clonal selection will be defined.
Duration: 1.7.2016 - 31.7.2020

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

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

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

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

New diagnostic and therapeutic tools against multidrug resistant tumors
Nové diagnostické a terapeutické nástroje v liečbe mnoholiekovej rezistencie nádorov
Program: COST
Project leader: RNDr. Jurkovičová Dana PhD.
Duration: 11.9.2018 - 10.9.2022

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

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

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

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

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

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

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

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

The total number of projects: 19