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Project

Institute of Molecular Biology

International Projects

PathogenTracker - Water/Wastewater epidemiology: Development of robust and reliable molecular detection systems for surveillance of disease outbreaks

Epidemiológia vody/odpadovej vody: Vývoj spoľahlivých molekulárno-biologických detekčných metód pre dohľad nad ohniskami epidémií

Duration: 1. 1. 2021 - 31. 12. 2023
Program: Bilaterálne - iné
Project leader: Dr. Pangallo Domenico DrSc.
Annotation:Before being a health emergency, the COVID-19 pandemic should be considered as a problem related to the unsustainable exploitation of the environment. We retain that the monitoring of the environmental microorganisms and viruses can be a suitable solution to face the next pandemics. Early warning systems are necessary to assess the health status of our cities using the samples recovered from sewage, wastewater, and aquatic environments. These systems can be based on reliable and quick molecular approaches that consent to make prompt decisions against the spreading of dangerous outbreaks. In our project, these molecular systems will be targeted to antibiotic-resistant bacteria (ARB), Dengue virus (DENV), and SARS-CoV-2. ARB are already a real threat, and many pandemics that have not made so much clamor in media occur periodically. DENV is another dramatic reality in many countries (including Taiwan) of tropical and subtropical regions, but by climate change and globalization, this threat can readily spread to other world regions. SARS-CoV-2 is new, and unfortunately, no therapy and vaccine are available at the moment. Through the cooperative works, we will develop and optimize several molecular approaches based on qPCR and RT-qPCR techniques. Such PCR assays will reveal and quantify the described pathogens, and they will be coupled with internal amplification controls able to guarantee their efficiency. Our investigation will be completed by the in-depth analysis of viral and microbial communities, including the resistome. This analysis will consent better to understand the viral and bacterial interactions in studied environments. For this purpose, two different high-throughput sequencing platforms, MinION and NovaSeq 6000, will be used.

ML4Microbiome - Statistical and machine learning techniques in human microbiome studies

Štatistické techniky a techniky strojového učenia v štúdiách ľudských mikrobiómov

Duration: 22. 2. 2019 - 21. 2. 2023
Program: COST
Project leader: Mgr. Kľučár Ľuboš PhD.

SuWaCer - Sustainable Water Reclamation Based on Ceramic Membrane Filtration

Trvalo udržateľná regenerácia vody založená na filtrácii keramickými membránami

Duration: 1. 4. 2020 - 31. 3. 2023
Program: Bilaterálne - iné
Project leader: Dr. Pangallo Domenico DrSc.
Annotation:Microplastics are a source of concern since they pose threats to aquatic species as well as human being. They not only contribute to accumulation of plastics in the environment, but due to absorption they can also contribute to spreading of micropollutants to the environment. Studies have shown that wastewater treatment plants are responsible for releasing micropollutants to the environment. Therefore, both detection and removal of microplastics from wastewater treatment plants are of paramount importance. Although the primary treatment process is efficient in removing microplastics of larger size, and microplastic fibers, it doesn’t remove small shaped microplastics. To remove very small shaped microplastic fragments, and to have the highest rate of microplastic removal, membrane technology is the best available technology. Organic membranes can be used for this purpose. Nevertheless, they are damaged easily. Ceramic membranes, on the other hand, have many advantages when compared to organic membranes such as higher abrasion resistance, chemical resistance, ability to be used at a very wide pH range (0 to 14), higher resistance to ozone and chloride, allowing the disinfection of water, and higher thermal resistance. In the light of this information, the aim of this project is to develop a robust durable ceramic membrane which will remove microplastics from secondary treated wastewater. To achieve this aim, tubular ceramic membranes with ultra and nanofiltration layers will be synthesized, and secondary treated wastewater will be treated with these membranes at lab and pilot scale for the removal of microplastics. The cyto-toxicity, genotoxicity and oxidative stress of micro/nanoplastics on human cells will be assessed, previously in vitro and then using the water of the wastewater pilot scale plant. In addition, also the antimicrobial properties of the membrane will be assessed, evaluating the microbial communities’ changes before and after the ceramic membrane treatment.

National Projects

How the cell finds the asymetric site of septation during sporulation of Bacillus subtilis

Ako bunka nájde miesto asymetrického delenia počas sporulácie Bacillus subtilis.

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Barák Imrich DrSc.
Annotation:Under nutrient rich conditions, bacteria grow and multiply by a process of cell expansion followed by division at mid-cell to generate identical daughter cells. When starved, bacteria slow down their metabolism and adopt various strategies to survive. Some bacteria have the capacity to form dormant cell forms called spores. The durability of spores is leading to the development of spores as delivery systems for vaccines. Sporulation in the rod-shaped bacterium Bacillus subtilis is a starvation response. It begins with an asymmetric cell division giving rise to a smaller forespore that lies side-by-side with a larger mother cell. Each compartment differs and both cells have different fates. This project proposes to study how the cell finds the asymmetric site ofseptation and how the asymmetric septum forms. In frame of the project, it is planned to study the crucial cell division proteins, peptidoglycan synthesizing machinery as well as cell shape-determinant proteins.

Amylolytic enzymes – thousands of sequences, hundreds of structures, dozens of specificities – and what about evolution...?

Amylolytické enzýmy – tisíce sekvencií, stovky štruktúr, desiatky špecificít – a čo evolúcia...?

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: prof. Ing. Janeček Štefan DrSc.
Annotation:The project is oriented towards the in silico study of amylolytic enzymes. They are starch hydrolases and related enzymes active to starch, glycogen and other alpha-glucans. They are not only hydrolases (EC 3), but also transferases (EC 2) and isomerases (EC 5). Amylolytic enzymes employing the retaining mechanism (producing alpha-glucans) are in the centre of attention. Based on their sequences, they are classified into glycoside hydrolase (GH) families, namely: GH13 – the main alpha-amylase family (~94700 sequences; >30 enzyme specificities) and GH57 – the second alpha-amylase family (~2750 sequences; <10 specificities). The main goal of the project is, based on detailed bioinformatics analyses of sequences and structures of amylolytic enzymes in relation to their enzyme specificity, to contribute significantly to the overall knowledge of biological processes, these enzymes are involved in. Results will be usable mainly in their faster and financially more appropriate biochemical characterization.

CELLDIV - Asymmetric cell division during bacterial endospore formation

Asymetrické bunkové delenie počas tvorby bakteriálnej endospóry

Duration: 1. 7. 2019 - 30. 6. 2023
Program: APVV
Project leader: RNDr. Barák Imrich DrSc.
Annotation:Bacillus subtilis is an internationally-recognized model organism, whose physiology, biochemistry and genetics has been studied for many years. This organism is used for decades to study the mechanisms of cell division and especially differentiation process, called sporulation. During this process very resistant spores are developed which can lie dormant and then germinate. This resistance of spores presents threats as well as potential benefits to human health and welfare. Botulism and tetanus are infectious diseases transmitted by spores, while spores of Clostridium difficile are responsible for hospital-acquired infections that are harmful to patients and which are expensive to treat and eradicate. Spores of Bacillus cereus cause food poisoning and present a challenge to the food industry, while spores of B. anthracis, which causes anthrax, are a concern because of their potential use as agents of bioterrorism and biowarfare. In contrast, the durability of spores has seen their development for use in nano-biotechnology and as probiotics in the food industry. Meanwhile their temperature resistance and capacity to resist dessication is leading to the development of spores as delivery systems for vaccines. Despite intensive research in the field of B. subtilis sporulation, there are still crucial molecular details missing in the complex mosaic of this process. Probably one of the most controversial questions about the cell division of Bacillus subtilis, a rod-shaped bacterium, concerns the mechanism that ensures correct division septum placement – at mid-cell during vegetative growth but closer to one end during sporulation. This project proposes to study the mechanisms of asymmetric septum formation and early stages of sporulation in B. subtilis. The aims of the project should be achieved by employing wide range of molecular biology, biochemical, genetic, structural biology and most advanced microscopy techniques.

Bio-cleaning of colored stains on historical documents: microbial, enzymatic, and chemical approaches

Bio-čistenie farebných škvŕn na historických dokumentoch: mikrobiálne, enzymatické a chemické prístupy

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: Dr. Pangallo Domenico DrSc.
Annotation:Colored stains on historical documents and books are a worldwide problem. They have microbial or synthetic origin and different chemical compositions depending by various factors. It is necessary to develop cost-effective techniques facilitating reliable and gentle removal of colored stains from the surface of historical items. Some enzymes, belonging to peroxidase and laccase groups, have the ability to decolorize various kinds of dyes. Certain are commercially available, while others could be extracted from a large range of microorganisms, mainly Basidiomycota. We shall utilize these enzymes as active components of tailored techniques to remove the stains without interfering with fragile and precious historical objects. In the frames of this research project we will primarily investigate: the selection of peroxidase / laccase producing microorganisms for the production of microbial enzymatic extracts and their application for removing colored stains from the surface of historical objects.

DIAMICROBIOTA - Gut microbiota and diabetic peripheral neuropathy: effect of cemtirestat in rat models of diabetes.

Črevná mikrobiota a diabetická periferálna neuropatia: účinok cemtirestatu v potkaňom modely diabetu.

Duration: 1. 8. 2021 - 30. 6. 2024
Program: APVV
Project leader: Dr. Pangallo Domenico DrSc.

AnCatSyn - Deciphering ancestral sequences of heme catalases for inferring their evolution mainly in emerging pathogens and selecting unique candidates for synthetic biology.

Dešifrovanie ancestrálnych sekvencií hémových kataláz pre rekonštrukciu ich evolúcie najmä v patogénoch a výber jedinečných kandidátov pre syntetickú biológiu.

Duration: 1. 1. 2022 - 31. 12. 2025
Program: VEGA
Project leader: RNDr. Zámocký Marcel DrSc.

PreveLynch - -

Dlhodobý strategický výskum a vývoj zameraný na výskyt Lynchovho syndrómu v populácii SR a možnosti prevencie nádorov spojených s týmto syndrómom

Duration: 1. 1. 2020 - 30. 6. 2023
Program: Štrukturálne fondy EÚ Výskum a vývoj
Project leader: Dr. Pangallo Domenico DrSc.

PLASARS - The double-edged sword of the plasminogen system: From homeostasis maintenance to COVID-19

Dvojsečný meč plazminogénového systému: Od udržiavania homeostázy po COVID-19

Duration: 1. 8. 2021 - 30. 6. 2025
Program: APVV
Project leader: Mgr. Leksa Vladimír PhD.
Annotation:The 2020 COVID-19 pandemic has affected the whole world. In addition to emerging vaccines, there is an urgent need for specific therapeutics that would block the SARS-CoV-2 spreading. Proteases responsible for the priming of SARS-CoV-2, and consequently for its higher virulence, appear as a rational therapeutic target for the clearance of SARS-CoV-2 infection. Accordingly, selective inhibitors of those proteases represent potential tools for prevention and treatment of COVID-19. Plasminogen activation system is well characterized for its functions in fibrinolysis and cell migration; however, it might also be misused for the virus priming. Thus, plasmin is a doubleedged sword. On one hand, it is essential for a plethora physiological processes; on the other hand, it might be involved in pathogenesis. The ultimate objective of the project is to study in detail both sides of the plasminogen system reflected in health and disease, respectively. First, the project will focus on unravelling molecular pathways whereby Plg system plays in homeostasis maintenance, namely in efferocytosis – i.e. a removal of apoptotic cells. Second, the project aims to provide novel natural inhibitors for pharmacological modulation of the SARS-CoV-2 host cell entry via the blockade of proteolytic priming of virus. The project proposal emanates from our long-term continual research in the field of the plasminogen system, and solid preliminary data. Project achievements will be of high interest for scientists in basic research, but also for medical doctors and pharmacological companies. Our goals are not exclusive; there is a substantial integration at the level of underlying cellular and molecular mechanisms; likewise, there is one between health and disease.

StainsAway - Colored stains on historical papers: biological and chemical characterization coupled with removal solutions

Farebné škvrny na historických papieroch: biologická a chemická charakterizácia spojená s ich odstraňovaním

Duration: 1. 7. 2020 - 30. 6. 2023
Program: APVV
Project leader: RNDr. Bučková Mária PhD.
Annotation:The microbial colored stains on historical papers (documents and books) are a worldwide problem, which may considerably vary due to regional climate and microbial diversity. It is necessary to develop a cost-effective technique facilitating effective yet gentle removal of the colored microbial stains from the surface of historical papers. The current knowledge indicates that some enzymes, belonging to peroxidase and laccase groups, have the ability to decolorize various kinds of dyes. Some of them are commercially available, while others can be extracted from a large range of microorganisms that produce them, mainly Basidiomycota. Therefore, it is possible to exploit this property in order to remove microbial pigments or colorants. For this purpose, we shall utilize enzymes as active components of tailored techniques to remove the stains without interfering with or destroying the fragile and precious paper of historical documents and books. In frames of the research project, in addition to production of enzymatic extracts and their application, several other aspects will be investigated, such as: isolation of pigment / color producing microorganisms responsible for the microbial stains on paper; selection of peroxidase /laccase producing microbial isolates; chemical composition of colored stains on real paper items and on model paper samples; development of a non-destructive strategy for identifying the stains directly from historical items. The gained knowledge and developed tools will immediately help Slovak restorers and conservators, which are involved in the project (Academy of Fine Arts and Design in Bratislava; partner of the project), and also other institutions as for example Slovak National Archives and the University Library in Bratislava. Moreover, the international cultural protectors will also benefit from the developed approaches.

FUNPOXHYB - Fungal Hybrid Heme Peroxidases from Primeval Forest with Application in Environmental Biotechnologies

Hybridné hémové peroxidázy húb z pralesa s využitím v environmentálnych biotechnológiách

Duration: 1. 7. 2021 - 30. 6. 2025
Program: APVV
Project leader: RNDr. Zámocký Marcel DrSc.
Annotation:Hybrid heme peroxidases (EC 1.11.1.7) are newly discovered specific oxidoreductases capable of cleaving reactive peroxide bonds in inorganic as well as organic compounds. Concomitantly to this cleavage they oxidize mainly organic compounds forming radical products that can enter polymerization reactions. Over 260 complete sequences from various regions of whole genome DNA were discovered. After their RNA splicing and translation in corresponding protein sequences they exhibit a high level of conservation. So far they were discovered solely in the kingdom of fungi. According to their typical essential sequence patterns responsible for heme binding they all belong to the large peroxidase-catalase superfamily couting currently over 41000 representatives from prokaryotes and eukaryotes. With their catalytic activity hybrid peroxidases represent efficient extracellular enzymatic antioxidants with broad application in defence against toxic effects of the oxidative stress. Recently, their expression and function was described in phytopathogenic fungi. The objective of our proposed project is the discovery of complete DNA gene clusters, corresponding mRNA transcripts and translated secreted isozymes of hybrid heme peroxidases among non-pathogenic fungi isolated from unique primeval forest biotopes of Slovakia. Our goal is to obtain a stable level of expression for selected recombinant hybrid peroxidases with highest level of catalytic efficiency typical for this subfamily. We aim to purify sufficient amounts of this unique enzymatic antioxidants to allow the resolution of 3D structure from produced protein crystals. This shall lead to the explanation of their peculiar reactivity on the base of structure-function relationships in the conserved catalytic centre. No such crystal structure for any hybrid peroxidases is known yet so its availability for unique peroxidases from primeval forest biotopes will allow great future applications in green biotechnologies.

REZTEST - Identification of new treatment options in refractory testicular germ cell tumors

Identification of new treatment options in refractory testicular germ cell tumors

Duration: 1. 7. 2021 - 30. 6. 2025
Program: APVV
Project leader: Mgr. Kľučár Ľuboš PhD.
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.

IntMmiMito - Interaction of Mmi1/TCTP protein with mitochondria

Interakcia proteínu Mmi1/TCTP s mitochondriami

Duration: 1. 7. 2022 - 30. 6. 2025
Program: APVV
Project leader: RNDr. Pevala Vladimír PhD.
Annotation:Mmi1 (Mitochondria and microtubule interacting protein) is a yeast ortholog of human translationally-controlled tumor protein (TCTP) that is a conserved and highly expressed protein in mitotically active cells and cancer cells. It influences key biological processes and, importantly, it has been suggested as a target for cancer therapy. Nevertheless, despite its great potential in human medicine TCTP still remains an enigmatic protein, because not all its roles in cell are fully understood or even known. The results indicate that yeast ortholog Mmi1 protein serves as a stress sensor that can relocalize from cytosol to mitochondria. Mitochondria are essential organelles that dominate life-and-death decision processes in the cell and Mmi1 likely inhibits cell death (apoptosis) upon binding to mitochondria. However, the mechanism of Mmi1 binding to mitochondria as well as its exact effect(s) on mitochondria are very little understood. Here, we will use a model organism yeast Saccharomyces cerevisiae and human cells to study Mmi1/TCTP binding and interaction with mitochondria. The obtained results will extend our knowledge of Mmi1 interaction with mitochondria and also help us to better understand strong anti-apoptotic activity of TCTP in human cells that is a critical factor for, e.g. cancer growth and spreading.

Lactoferrin and lactoferricin as natural plasmin inhibitors: From the structure resolution to therapeutic applications

Laktoferín a laktofericín ako prirodzené inhibítory plazmínu: Od určenia štruktúry po terapeutické aplikácie

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: Mgr. Leksa Vladimír PhD.
Annotation:The glycoprotein lactoferrin (LF), a member of the transferrin family, is present in human milk, secondary granules of neutrophils, exocrine secretions, and mucosal surfaces in respiratory, urinary-reproductive and intestinal tracts. Since its discovery, more than 70 years ago, a plethora of functions have been attributed to LF, such as antimicrobial, antiviral, antiparasitic, antioxidant, antitumor, or immunomodulatory activities. Many of them depend either on the ability of LF to sequester iron, or on the binding capacities of a positively charged region located in the N-terminal domain, wherefrom the natural antimicrobial peptide lactoferricin (LFC) is derived as well. Recently, we have attributed to LF a novel function in fibrinolysis: it can directly bind the serine protease plasminogen (Plg), a major component of fibrinolytic system, and inhibit Plg activation to its active form plasmin (Plm). This system is physiologically crucial for blood clots resolution, tissue homeostasis or inflammation, but it might be implicated also in pathological processes, such as tumour growth or bacteria invasion. In the proposed project we plan to characterize in detail the physical interaction of LF/LFC with Plg, describe its functional relevance in regulation of immune responses, and delineate its possible therapeutic applications.

SafeCheese - Microbial contaminants in traditional Slovakian cheeses: their elimination by scientific tools based on quantitative analysis and mathematical modelling

Mikrobiálne kontaminanty v tradičných slovenských syroch: ich eliminácia vedeckými nástrojmi založenými na kvantitatívnej analýze a matematickom modelovaní

Duration: 1. 7. 2020 - 30. 6. 2023
Program: APVV
Project leader: Dr. Pangallo Domenico DrSc.
Annotation:The microbiological safety of traditional Slovak cheeses (“bryndza”, “oštiepok”, “parenica”, “korbáčiky”) has increased in recent years due to modifications in production technology and improved hygiene conditions. Nevertheless, in the case of the traditional method of production from unpasteurized ewe's milk, there is a continuing threat of enterobacteria and toxinogenic staphylococci, which are permanently present at relatively high levels in the initial raw material. In recent years, microorganisms capable of long-term persistence in a production environment, such as the dangerous pathogenic bacterium Listeria monocytogenes, have been associated with these microorganisms, which endanger the safety and quality of the products. Filamentous fungi have to be generally eliminated from eukaryotic microorganisms due to undesirable surface growth. Wild strains of Mucor circinelloides and Geotrichum candidum appear to be, due to their rapid growth, indicative in cheeses, despite their involvement in the maturing of lump cheeses. The aim of the project will be to characterize the growth and reproduction of these microorganisms in media, milk and cheese depending on conditions (temperature, pH, aw) using predictive microbiology and mathematical modelling procedures. Part of the research will be focused to definition of conditions for their reduction and elimination. The acquired knowledge will be a basis for increasing of microbiological safety and quality of traditional Slovakian cheeses.

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
Program: APVV
Project leader: Mgr. Kľučár Ľuboš 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.

MEDIHONEY - New insight into biochemical and functional properties of the major antibacterial components of honey

Nový pohľad na biochemické a funkčné vlastnosti hlavných antibakteriálnych zložiek medu

Duration: 1. 7. 2022 - 30. 6. 2026
Program: APVV
Project leader: Ing. Majtán Juraj DrSc.

Preparation of mutant lytic and replication proteins of bacteriophages and their antibacterial potential

Príprava mutantných lytických a replikačných proteínov bakteriofágov a ich antibakteriálny potenciál.

Duration: 1. 1. 2022 - 31. 12. 2025
Program: VEGA
Project leader: RNDr. Bukovská Gabriela CSc.
Annotation:The project follows the study of bacteriophages and their lytic and replication proteins. The main goal of the project is the preparation of proteins with a new specificity, increased catalytic and inhibitory activity against bacteria and verification of their antibacterial potential against pathogens. New hybrid proteins will be prepared by combination of catalytic and binding domains of characterized five endolysins. Increase in lytic activity and change of the specificity of the endolysins will be achieved by site-directed mutagenesis in the active site in the catalytic domains of muramidases, glycosylhydrolases and endopeptidase. We will also prepare the helicase mutants using directed mutagenesis. By modeling the properties of helicase, we will obtain new knowledge about the replication and replication mechanism of phage DNA, and about the interactions of phage and bacterial proteins, or inhibitors that are responsible for shutting down the replication mechanism and life processes of the bacterial host.

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
Program: APVV
Project leader: RNDr. Kormanec Ján DrSc.
Annotation:Bacteria of the genus Streptomyces are dominant producers of secondary metabolites with a wide range of biological activities. Genes for these metabolites are physically clustered. The aim of the project is the preparation and characterization of new antibiotics and antitumor agents by manipulation of secondary metabolite genes and synthetic biology methods. The project builds on the previous APVV project, where we determined the genomic sequence of our model strain S. lavendulae subsp. lavendulae CCM 3239, as well as its transcriptome in wild-type and mutant for the global regulator of secondary metabolism. In addition to the cluster for the unique antibiotic auricin, we have bioinformatically identified 30 gene clusters for potentially new secondary metabolites that are silent under laboratory conditions. The aim of the project will be to activate them by integrating strong promoters in front of genes for positive pathway-specific regulators or biosynthetic operons and charaterizing induced biologically active substances. The clusters will be cloned and integrated into the genome of the S. lividans RedStrep heterologous strain to genetically modify them to produce more potent biologically active agents. The structure of auricin and the organization of its gene cluster suggested a unique mechanism for its biosynthesis. The aim will be to characterize this biosynthesis and biological properties of prepared auricin intermediates. We previously successfully introduced the methodology of synthetic biology for the formation of new secondary metabolites. The aim will be to use this approach for characterization of auricin biosynthesis as well as for the production of new biologically active substances using a combination of genes for auricin and other polyketide antibiotics. Our results will contribute to the knowledge of secondary metabolite biosynthesis and may reveal new biologically active substances with efficient therapeutic properties.

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Regulácia interakčnej špecificity multi-PDZ proteínov

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: Mgr. Baliová Martina PhD.

Signal cascades of regulation of sigma factors of RNA polymerase in response to stress, cell and physiological differentiation in soil bacteria of the genus Streptomyces

Signálne kaskády regulácie sigma faktorov RNA polymerázy pri odozve na stres, bunkovej a fyziologickej diferenciácii u pôdnych baktérií rodu Streptomyces

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: RNDr. Kormanec Ján DrSc.
Annotation:In natural environment, bacteria are exposed to various stresses. Response to these stresses is mainly mediated by stress-response sigma factors of RNA polymerase. The Streptomyces coelicolor genome encodes up to 9 homologues of these sigma factors and a large number of their regulators (anti-sigma factors, anti-anti-sigma factors and signal PP2C phosphatases). Previously, we have characterized the role of these sigma factors, demonstrated their dual role in stress and differentiation, as well as their regulatory interconnection. Using several approaches, we have demonstrated interactions between all sigma factors, anti-sigma factors and anti-anti-sigma factors, as well as the phosphorylation of anti-anti-sigma factors with multiple anti-sigma factors, suggesting a complex regulation. The aim of this project is to further characterize these sigma factors, their complex regulation and their activation in response to a specific stress or differentiation signal through signal activating PP2C phosphatases.

STRAKA - Tree and country - influence of trees on diversity of soil microorganisms in agricultural land

Strom a krajina – vplyv drevín na diverzitu pôdnych mikroorganizmov v poľnohospodárskej krajine

Duration: 1. 7. 2021 - 30. 6. 2025
Program: APVV
Project leader: RNDr. Zámocký Marcel DrSc.

BryndzaStart - Microbial starters and adjunct cultures for production of Slovakian bryndza cheese with traditional organoleptic properties

Štartovacie a prídavné kultúry na výrobu slovenskej bryndze s tradičnými organoleptickými vlastnosťami.

Duration: 1. 7. 2021 - 30. 6. 2024
Program: APVV
Project leader: Dr. Pangallo Domenico DrSc.

Study and characterization of Clostridioides difficile Min proteins.

Štúdium a charakterizácia Min proteínov z Clostridioides difficile.

Duration: 1. 1. 2022 - 31. 12. 2025
Program: VEGA
Project leader: Mgr. Labajová Naďa PhD.
Annotation:Proposed project is focused on the study of self-organization capability and mechanisms involved in functioning of Min system proteins from Clostridioides difficile. C. difficile is a widely distributed human pathogenic bacterium. Especially after antibiotic treatment, it can dominate over normal gut microbiota and produce toxins, which cause severe diarrhoea, colon inflammation or even death to patients. The Min system is a well-conserved protein complex, which regulates positioning of the cell division septum in rod-shaped bacteria. It acts as a negative regulator of cell division, which blocks division septum formation at unwanted positions. C. difficile Min protein complex involves homologues from gram-positive, as well as gram-negative bacteria, and thus represents a unique, so far not described Min system. Understanding the mechanisms involved in C. difficile cell division regulation is of high importance and can lead to development of more targeted and effective drugs against C. difficile infections.

Study of the effect of cardiac arrhythmia-associated mutations on the structure and function of the human ryanodine receptor 2

Štúdium vplyvu mutácií asociovaných so srdcovými arytmiami na štruktúru a funkciu ľudského ryanodínového receptora 2

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: Mgr. Bauerová Vladena PhD.
Annotation:The human ryanodine receptor 2 (hRyR2) is a calcium channel whose main function is to release calcium ions from the sarcoplasmic reticulum into the cytoplasm, making it responsible for regular heart function. More than 300 mutations have been identified in the gene of this protein which affect its function, thereby causing a number of diseases (ARVD/C2, CPVT1, SUO, SCD, SID). These lead to heart failure and, in many cases, human death. Most pathological mutations in the RYR2 gene appear in three clusters, one each in the N-terminal, central and C-terminal regions. The main aim of this project is to study selected mutations associated with heart arrhythmias using in vitro and in silico approaches. The project will significantly contribute to the characterization of selected mutations at the biochemical, biophysical and structural levels and will help to understand the channel opening/closing processes in the above-mentioned pathological conditions.

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Úloha N-terminálnej fosforylácie a prirodzenej proteínovej neusporiadanosti v regulácii stability transportérov neurotransmiterov.

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Jurský František CSc.

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Využitie biokompatibilných 2D nanomateriálov a nanočastíc ako ochrana pred biodeterioráciou rôznych druhov povrchov

Duration: 1. 1. 2022 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Bučková Mária PhD.

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
Program: APVV
Project leader: Mgr. Kľučár Ľuboš 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.

The development of new methods for assessing honey quality

Vývoj nových metodických prístupov na hodnotenie kvality medu

Duration: 1. 1. 2022 - 31. 12. 2025
Program: VEGA
Project leader: Ing. Majtán Juraj DrSc.

Interaction between proteases, chaperones and kinases in stress condition cause by pathological conditions.

Vzájomná inerakcia proteáz, šaperónov a kináz v mitochodriách pri strese spôsobenom patologickými stavmi.

Duration: 1. 7. 2020 - 30. 6. 2024
Program: APVV
Project leader: Ing. Kutejová Eva DrSc.

Projects total: 32