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The list of national projects SAS

Institute of Molecular Biology

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.

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.

Covid-19 and long covid at the molecular level - biomarkers, tools and targets for diagnosis and therapy

Covid-19 a dlhý covid na molekulárnej úrovni - biomarkery, nástroje a ciele pre diagnostiku a terapiu

Duration: 1.9.2023 - 31.8.2027
Program:
Project leader: Mgr. Leksa Vladimír PhD.
Annotation:The goal of the project is to characterize lactoferrin as a potential complementary medicine in both acute and chronic covid-19 disease. The project started in September 2023 with the entry of Mgr. Patrika Babulic for doctoral studies.

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: SRDA
Project leader: Dr. Pangallo Domenico DrSc.
Annotation:A microbial imbalance inside the gastrointestinal tract (dysbiosis) can be associated with metabolic disorders such as obesity, insulin resistance, diabetes and immunity dysfunction. However, these relationships are still controversial and need further investigation. The aim of this project is focused on better understanding of mutual interactions of gut microbiota and the diabetic state and to reveal their consequences on development of chronic diabetic complications with the main attention to peripheral neuropathy. Effects of cemtirestat, a novel aldose reductase inhibitor, on the above mentioned processes will be studied. The experimental data will produce valuable knowledge on the role of microbiota alterations in the etiology of diabetic peripheral neuropathy and indicate potential therapeutic approaches.

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.

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: SRDA
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.

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: SRDA
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.

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: SRDA
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.

G-quadruplex DNA for Genetic Engineering in Bacteria

Implementácia G4 DNA do genetického inžinierstva baktérii.

Duration: 1.11.2023 - 31.10.2028
Program: IMPULZ
Project leader: Mgr. Jamroškovič Ján PhD.
Annotation:Synthetic biology is an interdisciplinary and rapidly evolving field that studies the biological functions of naturally occurring phenomena and applies this knowledge in genetic engineering. The main task of the field is to engineer microorganisms with specific properties in order to synthesize various products, to increase sustainability in a bio-based economy, and to provide solutions to environmental challenges. These methods combine cascades of genes into genetic circuits, which provide the microorganisms with novel functions. The current challenge in synthetic biology is how to increase the complexity of regulatory regions in short DNA fragments. Alternative DNA structures that act as genetic regulators can meet this need, and one type of such structures are the four-stranded DNA complexes called G-quadruplexes (G4s). The main goal of the proposed project is to implement G4s as novel regulators in genetic circuits in bacteria and to combine these with other DNA-based regulators. To achieve this, I will study G4s to understand their biology, maintenance, and effects on basic cellular processes, such is replication and gene transcription. There is a substantial knowledge gap regarding the presence and function of G4s in bacteria, but studies in eukaryotic model systems provide strong evidence regarding their folding and biological functions during gene transcription. Therefore, I believe that the incorporation of G4s into genetic engineering methods will increase the tunability and versatility of the regulation of synthetic bacterial gene networks. My strategy is to use the Gram-positive spore-forming bacterium Bacillus subtilis as a model system. B. subtilis is an industrially important bacterium and is considered a universal cell factory for industry, agriculture, biomaterials, and medicine and has been used as a model system for studies of basic cell processes for more than 60 years. Therefore, any positive outcomes of this project will be directly transferable to existing biotechnologies.

Interaction of Mmi1/TCTP protein with mitochondria

Interakcia proteínu Mmi1/TCTP s mitochondriami

Duration: 1.7.2022 - 30.6.2025
Program: SRDA
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.

Molecular mechanism of measuring device for finding the proper site of bacterial asymmetric cell division

Molekulárny mechanizmus meracieho zariadenia na nájdenie správneho miesta bakteriálneho asymetrického bunkového delenia

Duration: 1.7.2023 - 30.6.2027
Program: SRDA
Project leader: RNDr. Barák Imrich DrSc.
Annotation:The capacity of bacterial spores to lie dormant and then germinate presents threats as well as potential benefits to human health and welfare. Many sporulating bacteria genera Bacilli and Clostridia, such as Bacillus cereus, B. anthracis, Clostridium difficile, C. botulinum, C. tetani, C. perfirngens cause serious infectious diseases. In contrast, the durability of spores has seen their development for use as probiotics in the food industry, and the temperature resistance of Bacillus subtilis spores and their capacity to resist desiccation is leading to the development of spores as delivery systems for vaccines. This is also a reason why this organism is used for decades to study the mechanisms of cell division and especially the differentiation process, called sporulation. In this project, we aim mainly to understand at the molecular level how bacteria can measure their length and find the proper site of septation with high precision. Specifically, we are concentrating on asymmetrically positioned sporulation septum formation in Bacillus subtilis. Understanding this mechanism is among one the most fascinating questions in bacterial developmental biology. The expected knowledge is mainly important from point of view of basic research. Nevertheless, the knowledge of protein’s function inhibition, involved in cell division and sporulation, can help to design new antibacterial drugs, especially against multidrug resistance endospore-forming pathogenic bacteria.

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: SRDA
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.

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: SRDA
Project leader: Ing. Majtán Juraj DrSc., MBA, FIFST
Annotation:Honey has long been used as a natural remedy in wound care management. Because of the global emergence of antibiotic-resistant bacteria, the interest in honey as a medical substance in the treatment of infected/non-healing wounds is rapidly increasing. Although, honey displays well-documented in vitro antimicrobial activities even against multi-drug-resistant bacteria, the mechanisms of antibacterial action of honey and its individual antibacterial compounds in clinical conditions are still not fully understood. We hypothesize that infected wound is not a hostile environment for honey major antibacterial components, such as bee-derived glucose oxidase (GOX) enzyme and methylglyoxal, a major antibacterial factor of non-peroxide manuka honey which serves as a base for medical grade honey. The project MEDIHONEY aims to dissect the antibacterial action of honey at the biochemical level and focuses on important but neglected aspects of antibacterial efficacy of different honey types in wound-like environments, elucidating the role of major honey antibacterial compounds in such environments. In this project, we will thoroughly assess the biochemical features and structure of GOX, an enzyme responsible for generating hydrogen peroxide in diluted honey, which allows its further usage in medicinal and biotechnological applications. A synthetic wound care product based on purified bee GOX and pro-oxidative polyphenols will be developed and tested in the project. Finally, the project will address the potential of honey to eliminate intracellularly localised Staphylococcus aureus in human keratinocytes, which may open up new avenues to use honey in the treatment of other topical disorders of the skin associated with bacterial infections (e.g. atopic dermatitis).

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.

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: SRDA
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.

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: SRDA
Project leader: RNDr. Zámocký Marcel DrSc.

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: SRDA
Project leader: Dr. Pangallo Domenico DrSc.
Annotation:The unique organoleptic properties of bryndza cheese traditionally produced in Slovakia guarantee its stable position on the national food market and also its acceptance as an item of Slovakian cultural heritage. In our previous national research projects, we identified microorganisms forming communities in ewes' lump cheese that is a basic intermediate material for production of bryndza cheese, we determined key aroma-active compounds contributing to its typical organoleptic profile and, based on the study of metatranscriptome, we deduced main players in metabolism of casein leading to important aroma-active compounds. The aim of the present research project will be to synthesize the previously gained knowledge, make use of the colletion of microbial isolates obtained in the previous research projects and to gain additional knowledge as well as obtain new strains of lactic acid bacteria, yeasts and filamentous fungi as candidate starter cultures. The presented research project will involve characterization of microbial communities and genetic characterization of microorganisms in natural whey cultures and in maturation chambers, which will be based on utilization of culture-based microbiological methods and modern molecular-biological methods including high-throughout sequencing. Diversity of bacteriophages will be also studied, as these affect microbial communities of cheeses and the success of starter cultures. Objective characterization of the aroma of model cheeses will be achieved by using gas chromatography – olfactometry with support of gas chromatography – mass spectrometry. The outcomes of the project will be a collection of microbial strains and of knowledge on their metabolic potential, including characteristics obtained in small-scale application, which will directly facilitate technical development of starter cultures for production of bryndza cheese with traditional organoleptic properties.

The stipend for a scientist threatened by the war in Ukraine č. 09I03-03-V01-00113

Štipendiá pre excelentných výskumníkov ohrozených vojnovým konfliktom na Ukrajine č. 09I03-03-V01-00113

Duration: 1.11.2022 - 31.10.2025
Program:
Project leader: RNDr. Moskalets Tetiana PhD.
Annotation:The major goals of the project are 1) the research on the milk glycoprotein lactoferrin as a potential drug for covid-19 disease and 2) the development of diagnostic tools for the so-called long covid (persistent covid). Specific objectives will include biochemical analyses, such as purification, preparation and characterization of peptides, proteins and other molecules, crystallographic studies, but also cellular models and functional assays.

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.

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Úloha mitochondriálnej proteázy Lon a fosforylácie proteínov mitochondriálneho nukleoidu v homeostáze a udržiavaní mtDNA 2/0069/23

Duration: 1.1.2023 - 31.12.2026
Program: VEGA
Project leader: Ing. Kutejová Eva DrSc.

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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.
Annotation:The aim of the research is to gain new knowledges of 2D nanomaterials as antifungal tools from the perspective of advanced application for protection against biodeterioration of various surfaces and materials. We focus on monitoring antifungal activity of modern 2D nanomaterials and nanoparticles, which are MXenes and MoOx plasmon nanoparticles in combination with monoterpenoid phenolic compounds (thymol, carvacrol) and terpene alcohol (linalool), all from the Lamiaceae family, occurring naturally in nature. With combination of these biocompatible nanomaterials and terpenoid compounds we would like to achieve partial or complete suppression of microbiological damage to natural and modern building materials, such as wood, stone, ceramics with respect to ecology.

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: SRDA
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., MBA, FIFST

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. APVV-19-0298

Duration: 1.7.2020 - 30.6.2024
Program: SRDA
Project leader: Ing. Kutejová Eva DrSc.
Annotation:Many severe diseases, like cancer and neurodegenerative and mitochondrial diseases, are closely connected to the stress response. Mitochondria are crucially important organelles that provide an organism with energy and also serve as the main junctions of many metabolic and signaling pathways. Consequently, mitochondria have been found to undergo substantial functional changes in cancer cells. In a variety of cancers, mutations in the mitochondrial DNA (mtDNA) have been found that influence mitochondrial metabolism and biogenesis. Respiration defects closely related to mtDNA defects in cancer cells lead to a dependency on glycolysis and activation of kinase AKT resulting in drug resistance and a hypoxia survival advantage. Two major mitochondrial stress response components, heat shock proteins and LON protease, are components of the mitochondrial nucleoid, the large protein–DNA complex responsible for mtDNA stability and function. Mortalin, TRAP1, mitochondrial kinases like MtCK1, and the LON protease are all upregulated in several tumor cells and are known to facilitate tumor cell proliferation and survival. TRAP1 interacts with MtCK1, but phosphorylation of MtCK1 significantly alters this interaction. The LON protease is responsible for precisely regulating the TFAM protein, a major architectural nucleoid-formatting agent, which is critical for mtDNA stability and transcription. Phosphorylation of TFAM destabilizes its interaction with mtDNA. Both mitochondrial chaperones and LON were shown to be phosphorylated in cancer cells. Much has been already published on the structure and function of these proteins, but almost nothing is known about their possible interactions and cooperation. The proposed project will study how chaperones and LON act together in protein import, folding and degradation in mitochondria and how phosphorylation of particular serine and tyrosine residues influence all the processes mentioned above.

The total number of projects: 28