Projects

International

KeelBoneDamage – Identifikácia príčin a riešení poškodenia hrebeňa prsnej kosti u nosníc
Identifying causes and solutions of keel bone damage in laying hens
Program: COST
Project leader: RNDr. Košťál Ľubor CSc.
Annotation: The KeelBoneDamage COST Action will provide the European laying hen industry with the innovations in breeding, nutrition, and management necessary to resolve the problem of Keel bone damage (KBD) in order to meet the high standards of welfare and productivity demanded by the European community.The extremely high frequency and severity of KBD represents one of the greatest welfare problems facing the industry as suggested by several of the leading authorities in animal welfare, including the UK`s Farm Animal Welfare Committee and EFSA. More critically, KBD appears to be exacerbated by recent transitions imposed by EU legislation which banned the use of conventional battery cages from January 2012. Although conceived with the best of intentions and a bold step to improve hen welfare, the unexpected consequences are a blight on Europe`s moral standing and as a result of this well-intended legislation, the laying hen industry is now faced with the unexpected challenge of greatly increased KBD leading to reduced animal welfare and farm productivity. The proposed framework seeks to provide a platform for collaboration on the the causes of KBD and solutions to reduce their severity and frequency. The Action brings various participants with a diverse mix of disciplines, ages, and geographies together to facilitate novel and trans-disciplinary discussions that will lead to definitive and quantifiable outputs. Advancements will be performed in concert with industrial partners whom are leaders in the field ensuring that developments are directed into tangible outputs that improve animal welfare and farm productivity.
Duration: 18.10.2016 – 17.10.2020
GroupHouseNet – Synergia pre zabránenie poškodzujúcemu správaniu u skupinovo chovaných ošípaných a nosníc
Synergy for preventing damaging behaviour in group housed pigs and chickens
Program: COST
Project leader: RNDr. Košťál Ľubor CSc.
Annotation: The GroupHouseNet aim is to provide the European livestock industry with innovations in breeding and management for pigs and poultry that are needed for a successful transition to large group housing systems without necessitating painful tail docking and beak trimming. Allowing the animals greater opportunities to display their species-specific behaviour while avoiding the routine use of painful procedures, group housing of unmutilated animals sits at the core of the new animal welfare paradigm driven by consumer demand. Group housing is associated with increased risks of damaging behaviours among the animals, such as feather pecking, aggression and cannibalism in laying hens and tail biting, bellynosing, excessive aggression and cannibalism in pigs. Recent research suggests the key to reducing the incidence of these behaviours lies in refining and applying methods of genetic selection, and developing husbandry innovations that improve early and later life conditions – which is exactly what GroupHouseNet will use the COST Action framework and tools to do. GroupHouseNet brings together researchers and industrial partners dealing with animal breeding and genetics, animal nutrition, epidemiology, engineering, animal behaviour and welfare, epigenetics, immunology, (neuro)physiology, economics and ethics. To strengthen the scientific and technological basis in these areas the Action will facilitate knowledge sharing, creation and application in pigs and laying hens in both experimental and commercial environments. The activities will be conducted in an open, output-oriented transnational, multisectorial, and multidisciplinary research and development network emphasising COST Excellence and Inclusiveness Policy.
Project web page: http://www.grouphousenet.eu/
Duration: 2.3.2016 – 1.3.2020
Metabolizmus lipidov ako kľúčový regulátor mitochondriálnej funkcie
Lipid metabolisms as a crucial regulator of mitochondrial function
Program: Bilaterálne – iné
Project leader: Mgr. Balážová Mária PhD.
Duration: 1.3.2017 – 28.2.2020
FWF P28179-B30 – Vzťah medzi PDS a mitochondriami v procese epileptogenézy
The link between PDS and mitochondria in epileptogenesis
Program: Iné
Project leader: RNDr. Cagalinec Michal PhD.
Annotation: PDS are increasingly recognized as epileptogenic factors in acquired forms of epilepsies. Prevention of PDS provides a potential means to decrease the numbers of patients developing epilepsy after brain injuries. It is of crucial importance to understand the pathomechanisms of PDS formation (e.g. common molecular links converging in the aftermaths of hemorrhagic bleeding – both subarachnoidal and intracerebral – or of infection, ischemia,…). Since epilepsy develops only in a certain number of patients, i.e. about 20% after severe brain injury, it is of primary interest to define the factors that predispose to acquisition of an epileptic brain condition. A genetic influence has been noted with respect to this predisposition. The mitochondrial state may represent a critical determinant. Indeed, mitochondrial dysfunction is increasingly understood as a precipitating cause of epilepsy. However, the possibility that formation of PDS plays an essential role therein has not been addressed so far, and thus represents an innovative aspect in targeting epileptogenesis. The vital question is whether supporting mitochondrial function during a critical period after brain injuries can be used to prevent subsequent pathogenesis. Answering this question can be envisaged to provide invaluable insights in viable strategies to counteract acquired forms of epilepsies. Additionally, important information regarding mitochondrial implications in neuronal physiology and pathophysiology can be expected to also arise from our approach.
Duration: 1.1.2016 – 30.6.2018
Charakterizácia nových interakčných partnerov N-typu (Cav2.2) vápnikového kanála
Characterization of novel interaction partners of the N-type (Cav2.2) calcium channel
Program: Bilaterálne – iné
Project leader: doc. RNDr. Lacinová Ľubica DrSc.
Duration: 1.1.2016 – 31.12.2017
Prekurzory biosyntézy kardiolipínu: dôvody pre abnormálnu akumuláciu, vplyv na funkciu a morfológiu mitochondria
Precursors of cardiolipin biosynthesis: reasons for aberrant accumulation, effects on mitochondrial function and morphology
Program: Medziakademická dohoda (MAD)
Project leader: Mgr. Balážová Mária PhD.
Annotation: Defects in biosynthesis of cardiolipin (CL) influence mitochondrial structure and function and consequently the whole cell survival. CL absence, its peroxidation or interference of its acyl chain composition is coupled with mitochondrial dysfunction in various tissues. Abnormal metabolism of mitochondrial anionic phospholipids induces serious hereditary disorder, Barth syndrome. Pathogenesis of this disease is described as a lost ability of mitochondria to remodel the CL fatty acid residues. New findings on the yeast models however suggest that the impaired CL remodeling does not represent the primary reason for these mitochondrial dysfunctions. Despite the lowered level of CL, patients with Barth syndrome also exhibit accumulated CL precursor, monolyso-CL (MLCL). The aim of the project is to explore how the accumulation of two major CL precursors, phosphatidylglycerol and MLCL, itself influences the mitochondrial morphology and function. Expected results should significantly contribute to understanding of the molecular mechanisms leading to symptomatic manifestations of the disease.
Duration: 1.1.2015 – 31.12.2017
Štúdium CD molekúl na cicavčích spermiách
Study of CD molecules on mammanlian sperm
Program: Medziakademická dohoda (MAD)
Project leader: Ing. Jankovičová Jana PhD.
Annotation: In mammals, an essential part of fertilization represents gamete or molecule cooperation either on the cell or the whole body level. At present, several differentiation antigens potentially involved in these processes are considered. Many of CD molecules are immunologically active glycoproteins and some of them were found on the genital tract cells and tissues. However, no mechanism for gamete maturation or fertilization involvement has been described and moreover, their role on porcine and bovine spermatozoa has not been yet studied in the detail. Therefore, the analyses of differentiation antigens detected on epididymal, ejaculated, capacitated and acrosome-reacted porcine and bovine spermatozoa in vitro as well as the study of interaction between egg zona pellucida and spermatozoa could lead to better understanding to molecular basis of the reproduction process. Finally, obtained results could provide us useful information regarding the some cases of farm animals’ infertility.
Duration: 1.1.2015 – 31.12.2017
Vplyv lipidového zloženia plazmatickej membrány kvasiniek na rezistenciu voči antifungálnym liečivám a iným stresovým faktorom
Role of the lipid composition of the yeast plasma membrane on resistance to antifungal drugs and other stress factors
Program: Medziakademická dohoda (MAD)
Project leader: Mgr. Valachovič Martin PhD.
Annotation: Many clinical isolates of the pathogenic yeast Candida albicans are resistant to broad spectrum of drugs. The development of resistance involves not only the increased expression of membrane transporters exporting the drug but is also affected by lipid composition of the cell membrane.Yeast mutants deficient in ergosterol biosynthetic pathway show increased sensitivity to many toxic substances. PDR16 gene belongs to the genes potentially involved in sterol metabolism. Our previous research has shown that the biotechnologically important yeast Kluyveromyces lactis deficient in PDR16 gene has disrupted proper cellular membrane function and the cells are sensitive to a wide range of toxic substances. We would like to apply this knowledge to the pathogenic yeast C. albicans. Aim of the project is to study the physiological role of the CaPDR16 gene in relation to the cellular membrane functions and development of resistance to antifungal drugs.
Duration: 1.1.2016 – 31.12.2017
PUT771 – Štúdium mitochondriálnej dynamiky v transgénnom modeli Alzheimerovej choroby pomocou mikroskopie so super vysokým rozlíšením
Targeting mitochondrial dynamics in transgenic rat model of Alzheimer’s disease with superresolution microscopy
Program: Iné
Project leader: RNDr. Cagalinec Michal PhD.
Annotation: Alzheimer’s disease, the most prevalent form of dementia, involves selective neuronal loss, synaptic alterations, morphological and functional mitochondrial abnormalities and tau pathology. Mitochondrial distribution, morphology and mtDNA integrity is regulated by balanced fusion-fission cycling and motility of mitochondria. Microtubules, tracks for mitochondrial movement, are stabilized by tau protein. Truncated forms of tau destabilize the microtubular network, causing loss of mitochondria in axons and are proposed to be involved in synaptic dysfunction. Using advanced microscopic techniques, we wish to answer the following: Do the truncated forms of tau negatively impair dynamics, morphology and mtDNA content in synaptic mitochondria? Is this part of the pathomechanism underlying the loss of synapses and neuronal degeneration? Finally, as a possible therapeutic target, can we rescue neuronal degeneration and synaptic mitochondrial abnormalities by stimulating mitochondrial movement?
Duration: 1.1.2015 – 31.12.2016
BMPS – COST: Plynné prenášače, od základného výskumu po biologické aplikácie
COST: Gasotransmitters: from basic science to therapeutic applications
Program: COST
Project leader: RNDr. Ondriaš Karol DrSc.
Annotation: It is now clear that several “gasotransmitters” exist and this class of mediators also includes NO, CO and H2S. Several of the groups leading this research field are based in the EU, thus, the formation of a European network that collates scattered knowledge, resources and expertise on gaseous mediators will emcourage the dissemination of innovation, boost collaborations and increase the European competitiveness in this field.
Project web page: http://www.cost.esf.org/domains_actions/bmbs/Actions/BM1005
Duration: 6.5.2011 – 5.5.2015
Celgene
Program: Bilaterálne – iné
Project leader: doc. Ing. Breier Albert DrSc.
Duration: 1.10.2009 – 31.12.2014
AWARE – Výskum welfaru zvierat v rozšírenej Európe
Animal WelfAre Research in enlarged Europe
Program: 7RP
Project leader: RNDr. Košťál Ľubor CSc.
Annotation: The goal of AWARE is to promote integration and increase the impact of European research on farm animal welfare (FAW). It will do so through the development of Europe-wide networks of scientists, lecturers and students, and by establishing a network of stakeholders active in FAW knowledge transfer and implementation.AWARE actions will be organised in 3 mutually supportive Work Packages (WPs). WP A “Research” will enhance the integration of FAW research by fostering collaboration based on mutual recognition and by enhancing networking and proposal writing skills in motivated researchers throughout the enlarged Europe. WP B “Education” will promote cross-fertilisation in FAW university education, thus enhancing opportunities for young scientists in new and candidate countries to start research in FAW. WP C “Awareness and Implementation” focuses on enhancing public awareness, promoting implementation of EU policies, and facilitating uptake of FAW research. All 3 Work Packages proceed in 4 steps: 1. Mapping, 2. Establishing networks, 3. Improving skills and 4. Developing strategies for ongoing integration. Three horizontal activities support the WP’s: a MobilityDesk facilitates mobility of researchers and students; the Communication module supports internal and external communication; and Management takes care of project management and effective communication with theCommission.AWARE will increase the European research capacity in FAW activities, through integrating the underutilized human and knowledge potential in the new and candidate countries. The project will result in faster and more comprehensive FAW knowledge transfer across Europe. It will also build for the future by drawing young scientists into FAW research and providing a base for harmonized implementation of FAW legislation in the enlarged EU.
Project web page: www.aware-welfare.eu
Duration: 1.3.2011 – 28.2.2014
EUWelNet – Koordinovaná európska sieť pre welfare zvierat
Coordinated European Welfare Network
Program: Multilaterálne – iné
Project leader: RNDr. Košťál Ľubor CSc.
Annotation:
Duration: 31.12.2012 – 31.12.2013
HypoxiaNet – Vnímanie hypoxie, signalizácia a adaptácia
Hypoxia and oxygen sensing, signaling and adaptation
Program: COST
Project leader: prof. Ing. Križanová Oľga DrSc.
Project web page: www.hypoxianet.com
Duration: 1.7.2009 – 30.11.2013
MNT-ERA.Net II – Ultracitlivé, stabilné a jednoduché v použití biosenzorické hroty pre AFM
Ultra-sensitive, stable and easy to use AFM bio sensor tips
Program: 7RP
Project leader: Ing. Šnejdárková Maja CSc.
Duration: 1.1.2010 – 31.12.2012
Molekulárne mechanizmy regenerácie bazálnych ganglií u spevavcov
Molecular Mechanisms of Basal Ganglia Regeneration in Songbirds
Program: Bilaterálne – iné
Project leader: Mgr. Niederová Ľubica PhD.
Annotation: While studying the role the basal ganglia pathway in learned vocal communication, we discovered an unexpected phenomenon: following neurotoxic lesions, the avian striatum recovered itself and so did associated learned vocal behavior. This phenomenon, as far as we know, is unprecedented in the mammalian brain. Here we propose to investigate the mechanisms of this recovery and detemine whether this is in fact new neuron regeneration or neuron invasion from the surrounding areas. Further we will determine the time course of this recovery accompanied with behavioural (song) recovery. We will determine whether the cellular organization in the recovered striatum is the same as in intact striatum. Finally, we will test wheter the recovery is specific to neurotoxic lesions or it is a more general aspect of brain repair of the avian striatum. As the avian striatum contains neurons similar to their mammalian counterparts, the project is expected to impact our understanding of brain regeneration.The relevance of this research to public health is that we would find potential ways to repair damaged basal ganglia brain areas, and in particular for correcting speech deficits.
Duration: 1.7.2006 – 30.6.2011
EUGeneHeart – Genomika signalizácie v kardiomyocytoch pre liečbu a prevenciu zlyhania srdca
Genomics of Cardiomyocyte Signalling to Treat and Prevent Heart Failure
Program: 6RP
Project leader: Ing. Zahradníková Alexandra DrSc.
Annotation: The goal of the EUGeneHeart project is the development of new approaches to prevent and treat heart failure through analysis of the genomics of signalling.<cr>The strategy is based on the hypothesis that beneficial as well as maladaptive forms of hypertrophy exist and that heart failure is frequently preceded by maladaptive hypertrophy. We will dissect both adaptive and maladaptive signalling in hypertrophy to identify beneficial and maladaptive components of signal transduction in hypertrophy and heart failure.
Project web page: www.eugeneheart.eu
Duration: 1.1.2006 – 31.12.2010
CavNET – L-typ Ca2+ kanálov v zdraví a chorobe
L-type Ca2+ channels in health and disease
Program: 6RP
Project leader: doc. RNDr. Lacinová Ľubica DrSc.
Project web page: http://www.cav-net.org/
Duration: 16.12.2006 – 15.12.2010
Energetická výmena a cytoarchitektúra srdcových buniek. Vývojové zmeny a úloha cytoskeletu
Energetic cross-talks and cytoarchitecture of cardiac myocytes. Developmental changes and the role of cytoskeleton
Program: Medzivládna dohoda
Project leader: RNDr. Novotová Marta CSc.
Annotation: The objective of this collaboration is to understand the importance of the cytoarchitecture for energetic exchanges and for contractile efficiency. This project is aimed at correlating, during postnatal development in mice, the organization of cell architecture (quantified by electron microscopy) and functioning of energy cross-talks between organelles (measurement of calcium fluxes and contractility). This is a basic science study to explore relationships between cytoarchitecture, energy fluxes and contractility.A second part of the project will explore consequences of cytoskeletal protein knocking out on maturation of energy transfer systems. Finally, these studies will allow to understand the impact of architectural modifications on cardiac function and chronic pathology like heart failure.
Duration: 1.1.2008 – 31.12.2009
CONTICA – Kontrola vnútrobunkového vápnika a arytmie
Control of intracellular Calcium and Arrhythmias
Program: 6RP
Project leader: Ing. Zahradníková Alexandra DrSc.
Annotation: The major scientific objective of the CONTICA project is to determine the subcellular mechanisms underlying fatal arrhythmias related to dysfunction of the SR Ca2+ release channel (ryanodine receptor, RyR2).
Project web page: www.contica.eu
Duration: 1.2.2006 – 31.7.2009
Lokalizácia S100A1 v srdcových bunkách človeka
Localization of S100A1 in human heart muscle cells.
Program: Bilaterálne – iné
Project leader: MUDr. Uhrík Branislav CSc.
Duration: – 31.12.2008
Viaclieková rezistenia spojená s nadexpresiou P-glykoproteínu u hematologických malignanciách asociovaná s následkami ožiarenia po Černobylskej katastrófe
P-glycoproteín Mediated Multidrug Resistance in Radiation-Associated Hematological Malignancies Following the Chernobil Accident.
Program: NATO
Project leader: doc. Ing. Breier Albert DrSc.
Duration: 1.1.2007 – 31.12.2008
Reorganizácia vápnikovej signalizácie v zlyhávajúcom srdci.
Reorganization of calcium signaling in heart failure
Program: Medzivládna dohoda
Project leader: Ing. Zahradníková Alexandra DrSc.
Duration: 1.5.2005 – 30.4.2008
Bunková biológia neutrálnych lipidov u kvasiniek Saccharomyces cerevisiae
Cell biology of neutral lipids of the yeast Saccharomyces cerevisiae
Program: Medziústavná dohoda
Project leader: RNDr. Hapala Ivan CSc.
Duration: 1.9.2005 – 31.12.2007
Príprava robustného transformačného systému u buniek Methanothermobacter thermoautotrophicus
Preparation of robust transforming system in cells Mathanothermobacter thermoautotrophicus
Program: Medziústavná dohoda
Project leader: Mgr. Majerník Alan PhD.
Duration: 1.1.2001 – 31.12.2007
Meranie a monitorovanie welfaru hospodárskych zvierat
Measuring and Monitoring of Farm Animal Welfare
Program: COST
Project leader: RNDr. Košťál Ľubor CSc.
Duration: 1.10.2000 – 31.3.2006
Správanie a jeho fyziologické mechanizmy majúce vzťah k reprodukcii a welfaru u rodičov brojlerov
Behavior and its underlying physiological mechanisms related to reproduction and welfare problems in parent stock of meat type chickens
Program: Medzivládna dohoda
Project leader: RNDr. Košťál Ľubor CSc.
Duration: 1.6.2002 – 31.3.2006
C-RyR – Spriahnuté vrátkovanie vnútrobunkových vápnikových kanálov
Coupled gating between intracellular calcium release channels
Program: Multilaterálne – iné
Project leader: RNDr. Ondriaš Karol DrSc.
Annotation: We studied coupling of RyR
Duration: 1.1.2002 – 31.12.2005
Úloha iónových kanálov mitochondrií v ochranných mechanizmoch srdca
Role of mitochondrial channels in cardioprotection
Program: Multilaterálne – iné
Project leader: RNDr. Ondriaš Karol DrSc.
Duration: 1.1.2002 – 31.12.2004
RYR – Regulácia vápnikových iónových kanálov
Regulation of calcium release channels
Program: Multilaterálne – iné
Project leader: RNDr. Ondriaš Karol DrSc.
Annotation: Modulation of RyR by drugs was studied
Duration: 1.1.1998 – 31.12.2001

National

PuriTAAR – Štúdium mechanizmov účinku nových antidepresív: pyridoindolové deriváty a ligandy „trace amine-associated receptor one“ (TAAR1)
Investigation of the mechanism of action of novel putative antidepressant drugs: pyridoindole derivatives and trace amine-associated receptor-1 (TAAR1) ligands
Program: VEGA
Project leader: MMedSc Dremencov Eliyahu PhD
Annotation: The aim of the project will be to investigate the mechanism of action of the novel potential antidepressant drugs, such as pyridoindole derivatives and ligands of trace amine-associated receptor-1 (TAAR1). These drugs will be administered to the laboratory rats and their effects on their anxiety and depressive-like behavior and excitability of glutamate, serotonin, norepinephrine, and dopamine-secreting neurons in vivo and in neuronal primary cultures will be examined. This project will be performed in a collaboration with the industrial biopharmaceutical sector.
Duration: 1.1.2018 – 31.12.2021
SPLICONC – Objasnenie mechanizmov posttranslačnej regulácie faktorov zostrihu RNA pri udržiavaní stability genómu
Unravelling the mechanisms of post-translational regulation of RNA splicing factors in maintenance of genome integrity
Program: APVV
Project leader: Mgr. Bágeľová Poláková Silvia PhD.
Annotation: Several mutations in RNA biogenesis factors have been implicated in human cancers. Early studies linked RNA processing defects with genome instability phenotypes such as hyper-mutation and hyper-recombination. Since then, recent functional genomic studies have implicated several more aspects of RNA processing in genome instability and revealed that virtually every major aspect of RNA processing is potentially mutable to a genome instability phenotype and in some cases are coupling RNA processing defects to increased RNA:DNA hybrid- mediated R-loop formation, which in turn constitute a major source of genome instability across species. Despite it is now clear that RNA processing defects could destabilize genomes, the molecular mechanism of post-translational regulations of RNA processing and its connections to genome instability are not clear. Our project is aimed at a detailed analysis of the regulatory role of phosphorylation for functions of splicing factors that co-purified with the recently identified spliceosome-associated Nrl1 protein of fission yeast S. pombe. We showed Nrl1 protein be involved in suppression of accumulation of genome threating RNA:DNA hybrids, structures formed during RNA processing. The experimental approaches include protein purifications and phospho proteomics analysis, which will help us to identify post-translational modifications of splicing factors. Analysis of phenotypes of phospho mutants of splicing factors employ fluorescence/live-cell microscopy, analysis of splicing defects of these mutants using RT-PCR or transcriptome sequencing, followed by analysis of their sensitivity to DNA damaging agents and analysis of their defects in DNA repair pathways. The obtained data should bring especially completely new information concerning the regulatory roles of post-translational modifications associated with the defects of RNA processing leading to genome instability that may be important as possible targets for anti-cancer therapy.
Duration: 1.7.2017 – 30.6.2021
Regulácia pericelulárnej proteolýzy: od molekulárnych mechanizmov k novým subsetom imunitných buniek a terapeutickým nástrojom
Program: APVV
Project leader: RNDr. Zahradníková, ml. Alexandra PhD.
Duration: 1.7.2017 – 30.6.2021
Využitie myrozinázy na aktiváciu sulforafanu pre vývoj preparátu s preventívnymi účinkami nádorových ochorení
Program: APVV
Project leader: Ing. Sulová Zdena DrSc.
Duration: 1.7.2017 – 30.6.2021
Poškodzujúce správanie a welfare nosníc
Damaging behaviour and the welfare of laying hens
Program: VEGA
Project leader: RNDr. Košťál Ľubor CSc.
Annotation: The European laying hen industry is changing dramatically. After the EU ban on battery cages in 2012 layinghens were moved to large flocks in non-cage systems or furnished cages. Although this transition was led by anintention to offer animals greater opportunities to move and display their species-specific behaviour, is also posesan increased risk for damaging behaviour (feather pecking, aggressive behavior, cannibalism). Many EUcountries practice beak trimming in laying hens in order to minimize the damaging behavior consequences. Sincethis mutilation causes chronic pain, there is an increased demand to ban the beak trimming. Another problemassociated with the free movement of hens is the increased incidence of keel bone fractures. The aim of thisproject is to contribute to the understanding of factors influencing the development of damaging behavior andother problems associated with the changes in housing systems and to find the solutions for industry incollaboration with international consortia.
Duration: 1.1.2017 – 31.12.2020
Štúdium zmien expresie niektorých regulačných a štrukturálnych proteínov sprevádzajúcich expresiu P-glykoproteínu v leukemických bunkách
Study of changes in expression of some regulatory and functional proteins connected with the presence of P-gp protein in leukemic cells
Program: VEGA
Project leader: Ing. Sulová Zdena DrSc.
Annotation: Successful treatment of hematologic malignancies depends on the efficacy of chemotherapy. The P-glycoprotein (P-gp) overexpression is one of the most common causes of multidrug resistance (MDR) in leukemic cells. The presence of this protein in human and murine cell lines leads not only to resistance against P-gp substrates but significant is also its influence on cell response to substrates, which are not P-gp substrates. In our work, we found that P-gp expression in this cells was accompanied by changes in the levels/activities of regulatory or structural proteins. Some of these proteins are involved in the regulation pathway of apoptosis (Bcl-2 family proteins) or they can be the target of leukemia immunotherapy (CD33). The solving of this project have the potential to bring results clinically applicable in therapeutic protocols aimed to appropriate type of neoplastic diseases.
Duration: 1.1.2017 – 31.12.2020
Vplyv fotodynamickej terapie na vybrané molekulárne markery angiogenézy, fibroproliferácie a štrukturálne zmeny na modeli prepeličej chorioalantoickej membrány
The effect of photodynamic therapy on selected molecular markers of angiogenesis, fibroproliferation and structural changes on the Japanese quail chorioallantoic membrane model
Program: VEGA
Project leader: Mgr. Máčajová Mariana PhD.
Annotation: A lot of diseases are associated with increased angiogenesis, which is stimulated e.g. by VEGF signal pathway. New vessels provide nutrition to the proliferating tumor tissue and contribute to the formation of hematogenous metastases. Neoangiogenesis also plays an important role in the necrotic inflammation reparation process. Photodynamic therapy is a promising therapeutic mode of superficial tumors and focus infections that uses light-activated photosensitizer, and the subsequent photochemical reaction in the presence of oxygen causes destruction of target tissues. The aim of our project is to investigate the molecular and structural changes of the tissue after photodynamic therapy on the Japanese quail CAM model. The changes in molecular-biological parameters involved in the angiogenesis and fibroproliferation process will be monitored. Influencing the therapeutic effect and healing of tissues after administration of proangiogenic and antiangiogenic factors will be in the center of attention.
Duration: 1.1.2018 – 31.12.2020
Ovarian kryotech – Etablovanie techník kryouchovania ovariálného tkaniva hovädzieho dobytka pre účely génovej banky
Establishment of methodology of bovine ovarian tissue cryopreservation for the purposes of the gene banking
Program: APVV
Project leader: RNDr. Antalíková Jana PhD.
Annotation: The number of females of Pinzgau cattle breeds in Slovakia according to FAO database is around 2000 units,what is considered as a critical state within the animal genetic resources. Moreover, in Slovakia there are nofrozen embryos of Pinzgau cattle yet, which represents history, landscaping and indispensable part ofmountainous and mountain foothill areas of Slovakia. One solution to this problem is the cryopreservation of rarebiological material, which will play an important role in addressing the issue of preservation of animal geneticresources. Cryopreservation of ovaries, their surface tissues or ovarian follicles represents the future mainsource of female gametes. In frame of this methodology the oocytes isolated from frozen-thawed ovarianfragments will be selected for the quality, in vitro matured, fertilized with a bull semen and resultant zygotes willbe cultured to reach higher preimplantation stages of embryoa (blastocysts, expanded blastocysts). Theseresults will be compared with the embryo development obtained from the oocyte culture from fresh(noncryopreserved) ovarian follicles. These methodical approaches will be performed on biological material(ovaries) acquired from slaughtered cows at local abattoirs. Since our workplace already deals with the task ofanimal genetic resource preservation at the in situ and ex citu levels, we have all the conditions to solve thistask.
Duration: 1.7.2016 – 30.6.2020
Inovatívna MoS2 platforma pre diagnózu a cielenú liečbu rakoviny
Smart MoS2 platform for cancer diagnosis and targeted treatment
Program: APVV
Project leader: doc. Ing. Breier Albert DrSc.
Annotation: The goal of the proposed project is to develop a novel smart 2-dimensional multifunctional nanoplatform based on MoS2 for cancer cell detection and treatment. The MoS2 nanosheets prepared by liquid phase exfoliation and/or Li intercalation and modified for low toxicity and high biocompatibility will be chemically functionalized with antibodies sensitive to specific cancer cells and relevant cytotoxine. In comparison to graphene based nanosheets the MoS2 provides much stronger signal for the advanced laboratory diagnostics such as Raman spectroscopy, X-ray methods, SEM and TEM. Strong Raman signal and photoluminescence of MoS2 nanosheets will allow a label-free in situ tracking of the nanoplatform localization at the cell level. This will be one of the original project contributions to the knowledge of the cell interaction with the functional nanoplatform in general. The new quality of the laboratory testing of the nanoplatform interaction with the cancer cells may bring new knowledge and essential progress in the field of 2D nanoplatform generally. New knowledge is expected also in terms of a smart handling of biocompatibility and toxicity of the nanoplatform which is important for the nanoplatform cell internalization. Newly elaborated technological procedures will have direct implications for tailored 2D materials technology.
Duration: 1.7.2016 – 30.6.2020
Nové synergické protinádorové vlastnosti agonistov nukleárnych retinoidných X receptorov (RXR) ako následok vzniku "conditional" RXR-RAR heterodiméru v ľudských nádorových bunkách prsníka
Novel synergistic antitumour properties of nuclear retinoid X receptor (RXR) agonists as a consequence of the conditional RXR-RAR heterodimer formation in human breast cancer cells
Program: APVV
Project leader: Ing. Sulová Zdena DrSc.
Annotation: Nuclear retinoid X receptors (RXR) are considered to be important target molecules for treatment of several malignant diseases. Characteristic feature of RXR agonists is their capability to amplify the effect of endogenous ligand of nuclear retinoid receptors (RAR). The objective of the project proposal is the investigation of novel antitumour properties of the biologically active agonists of nuclear retinoid X receptors, which upon binding to RXR molecule function with the "partner" RAR receptors in the presence of all-trans retinoic acid as a "conditional" heterodimer. The object of investigation is a selected group of retinoid X receptors agonists of natural or synthetic origin. For a number of experiments, we will employ two different human breast cancer cell lines (estrogen receptor positive and estrogen receptor negative) in order to find cooperative effects of RXR agonist and RAR ligand at the RXR-RAR heterodimer leading to enhanced tumour cell growth inhibition or induction of apoptosis. The parallel objective of the project is investigation of the effects of the "supramolecular ligand/agonist" formation from a group of RXR agonists of natural or synthetic origin. We expect a number of original results yielding from experimental work that should contribute to the development of novel therapeutical potentialities for breast cancer treatment.
Duration: 1.7.2016 – 30.6.2020
Obranné mechanizmy neoplastických buniek proti chemickému stresu
Defense mechanisms of neoplastic cells against chemical stress
Program: APVV
Project leader: Ing. Sulová Zdena DrSc.
Annotation: Animal cells are disposing with large spectrum of defense mechanisms against damage induced by cytotoxic agents. These mechanisms are based on: i) ability of detoxification enzymes to modify the structure of cytotoxic agents; ii) ability of plasma membrane specialized transporters to eliminate the drugs from cell\’s intracellular space; iii| changes in expression of cytotoxic agents target proteins; iv| changes in regulatory pathways responsible for initiation of programed cell death mechanisms as response of cell damage induced by cytotoxic agents. Initiation of these mechanisms in neoplastically altered tissue leads to multidrug resistance (MDR) development. Reduced cell sensitivity to large group of structurally unrelated anticancer drugs with different mechanisms of pharmacological action is feature typical for MDR. If MDR is developed in cancer tissue, it represents real obstacle of effective chemotherapy. MDR could develop in cells of alla types of solid malignant tumors and also in blood malignancies. MDR development could be considered as adaptation of neoplastic cells on previously applied chemotherapy cycles. However, MDR could be present in neoplastic cells of patients that were not treated by anticancer drugs. MDR in this case represents specific phenotype of neoplasticaly altered cells. Targeted research on this topic represents aim of this project.
Duration: 1.7.2016 – 30.6.2020
HippoOR – Prenatálne a postnatálne účinky ligandov δ a µ opioidných receptorov na vývoj a funkciu hipokampu.
Prenatal and postnatal effects of δ and µ opioid receptor ligands on the hippocampal development and function.
Program: APVV
Project leader: doc. RNDr. Lacinová Ľubica DrSc.
Annotation: Ligands of opioid receptors δ (DOR) and μ opioid receptors (MOR) are commonly used in treatment of severe acute and chronic pain. DORs are involved also in mood disorders like depression and anxiety, which are related to the hippocampal function. Treatment with DOR ligands does not result in adverse effects including addiction, which are common with MOR ligands. However, much less is known about DOR – activated signaling pathways than about MOR – activated pathways. We will analyze the effect of acute (seconds to minutes) and chronic (hours to days) in in vitro and in vivo (prenatal and postnatal) administration of DOR ligands on the morphological and electrophysiological properties of rat hippocampal neurons and compare them with effects of MOR ligands and with effects of ligands specific for MOR-DOR heteromers. Further, involvement of calcium transporting proteins in signal transduction pathways activated by DORs and MORs ligands will be addressed by molecular biology methods. Possible remodeling of the dendritic spines will be investigated using transmission electron microscopy. Effect of DOR ligands on hippocampal plasticity in control and stressed rats will be examined using behavioral tests and molecular neuroscience techniques. Excitability will be investigated in primary culture of hippocampal neurons by patch clamp and in situ by in vivo electrophysiology. Both models enable to follow effects of acute and chronic drug application as well as possible receptor desensitization and offer complementary advantages. Primary neuronal culture is the possibility to visually identify neurons, characterize in details both action potentials and underlying ionic currents and to correlate electrophysiology and molecular biology on the same batch of neurons. In vivo electrophysiology offers the possibility to measure neuronal activity within its normal environment including all interactions with other brain parts. Finaly, behavioral studies enable investigation of an intact animal.
Duration: 1.7.2016 – 30.6.2020
Učenie a neuroná – Učenie a nervová plasticita spevavcov
Learning and neuronal plasticity in songbirds
Program: APVV
Project leader: Mgr. Niederová Ľubica PhD.
Annotation: Learning and plasticity in adult brain are important topics of the current neurobiological research. In the proposed project we focus on the study of neuroplasticity at regeneration of the striatal part of basal ganglia that control learned vocal communication. Birdsong is a form of learned vocal communication and although language has a unique cognitive architecture, birdsong has many parallels with human language. Therefore, the songbird model is often used in neuroscience studies. The present project is based on our previous results where we found that the striatal vocal nucleus in songbirds regenerates after injury and this regeneration is associated with song changes. The aim of the project is to elucidate the role of newborn neurons incorporated into the injured striatum in the relation to the learned vocal communication. We will study this role both via correlation studies comparing song variability and the rate of brain regeneration (measured by MRI) and via examining the effect of neurogenesis rate manipulation on song. We will focus on the changes in both song tempo and stuttering-like song with abnormal syllable repetition. Further, we will study the mechanism how striatum affects motor pathway necessary for song production. Particularly, we will investigate the repaired brain connectivity. Last, we will explore cognitive abilities of songbirds in relation to the changes in song after brain injury. These results will add to the knowledge of functional integration of the newborn neurons into brain circuitry and to the understanding of the role of neurogenesis in the regulation of behavior.
Duration: 1.7.2016 – 30.6.2020
INTERLIPID – Úloha medziorganelových interakcií v lipidovej homeostáze
The role of organelle interactions in lipid homeostasis
Program: APVV
Project leader: RNDr. Hapala Ivan CSc.
Annotation: Lipids are obligatory constituents of all living organisms serving as structural components of biomembranes,energy storage or signalling molecules. Despite the structural diversity of lipids and variability of environmental conditions affecting membrane functions, lipid composition of individual cell membranes is remarkably stable. This implies the existence of efficient homeostatic mechanisms maintaining optimal lipid composition in eukaryotic cells. These mechanisms are involved in the tightly regulated interplay between lipid biosynthesis, intracellular lipid trafficking, and lipid remodelling or degradation. Using the yeast Saccharomyces cerevisiae as a model eukaryotic cell the project is aimed at answering the question how interactions between intracellular organelles contribute to maintenance of lipid homeostasis. We will focus on three aspects of the problem of the lipid homeostatic mechanisms related to interorganelle interactions: 1) involvement of phosphatidyl inositol transfer proteins in maintaining membrane phospholipid composition; 2) the role of interactions between mitochondria and other intracellular organelles in the homeostasis of phosphatidylglycerol; and 3) the role of lipid droplets in ergosterol biosynthesis and sterol esterification.
Duration: 1.7.2016 – 30.6.2020
DARLINK – Vysoko selektívna liečba nádorových ochorení: komplexy endogénnych lipoproteínov s DARPinmi ako nová generácia transportných systémov pre cielený transport liečiv
Towards highly seletive cancer treatment: Endogenous lipoprotein-DARPin complexes as a new generation of targeted drug delivery vehicles
Program: APVV
Project leader: RNDr. Bilčík Boris PhD.
Annotation: Cancer chemotherapy generally exhibits a restricted therapeutic index. One of the underlying reasons is the lack of selective accumulation of drugs in cancer tissue. Thus, delivering anticancer drugs to a tumor in therapeutically effective concentrations, whilst sparing healthy tissue, is essential for the efficient treatment of solid cancer. The DARLIK project\’s ultimate goal is to develop a new technology for drug delivery resulting in a significantly improved selectivity of drug accumulation in cancer tissue and efficacy of chemotherapy. The proposed drug delivery vehicle (DARLINK) is a result of an original and innovative combination of a targeting scaffold protein, known as a Designed Ankyrin Repeat Protein (DARPin), and a lipoprotein-based drug carrier (LDL vehicle). It represents an emerging generation of targeted drug delivery systems, which will lead to a breakthrough in cancer treatment due to its optimal size as well as strong and selective binding to tumor- expressed receptors and capability to transport hundreds of drug molecules per vehicle. Moreover, DARLIK can be tailored to the mutated cancer cell receptors of individual patients, thus contributing to personalized medicine. This breakthrough nano-medical engineering technology is based on the unique expertise of the consortium, which consists of a trans-disciplinary knowledge in protein engineering, display technology, organic and polymer chemistry, biophotonics, cell biology, nanotechnology, computational modeling and medicine.
Duration: 1.7.2016 – 30.6.2020
Diastolická funkcia ryanodínového receptora a tvorba arytmogénnych vápnikových vĺn
Diastolic function of the ryanodine receptor and generation of arrhythmogenic calcium waves
Program: VEGA
Project leader: Ing. Zahradníková Alexandra DrSc.
Annotation: In some acquired and genetic arrhythmias, anomalies in calcium release occur during the diastole, which may result in formation of calcium waves that initiate cardiac arrhythmias. Proper diastolic function of the system of calcium homeostasis involves regulation of diastolic calcium release by ryanodine receptors. Anomalous calcium release from the viewpoint of calcium wave formation is not sufficiently understood. We will concentrate on determination of the relationships between localization of dyads as the sites of calcium release and formation of calcium waves, and on their development during maturation and physiological hypertrophy of myocytes. The outcome of the project will be a better understanding of the factors governing calcium homeostasis in cardiac myocytes and their impairment leading to calcium waves.
Duration: 1.1.2017 – 31.12.2019
Interakcie mitochondrií a jadier v procese speciácie.
Program: VEGA
Project leader: Mgr. Bágeľová Poláková Silvia PhD.
Annotation:
Duration: 1.1.2016 – 31.12.2019
Luminálna regulácia srdcového ryanodínového receptora a jej molekulárne mechanizmy
Luminal regulation of the cardiac ryanodine receptor and its molecular mechanisms
Program: VEGA
Project leader: Mgr. Gaburjáková Marta PhD.
Annotation: Ryanodine receptor type 2 (RYR2) plays unchangeable role in the process of excitation-contraction coupling in the heart. The physiologically relevant Ca2+ regulation of the RYR2 channel is predominantly determined by its robust cytosolic domain that harbors binding sites for cytosolic Ca2+. Less characterized channel regulation by luminal Ca2+ could be mediated by two mechanisms namely luminal Ca2+ binding on the luminal RYR2 face and binding of luminal Ca2+ emanating the RYR2 pore to the cytosolic channel face. Our aim is to examine a mutual relationship between these two mechanisms of the luminal regulation. The recent findings about the structure of Ca2+ binding sites on the RYR2 channel allow us to employ non-standard experimental conditions. We expect that trivalent cations and their interaction with the RYR2 channel will contribute to the reconciling of current controversial results and bring a comprehensive picture of the RYR2 Ca2+ regulation that has been implicated in heart diseases.
Duration: 1.1.2017 – 31.12.2019
Prítomnosť tetraspanínov a partnerských molekúl v rozmnožovacej sústave hovädzieho dobytka a ich účasť v interakcii gamét.
Tetraspanins and partner molecules presence in the reproductive system of cattle, their participation in gamete interaction.
Program: VEGA
Project leader: RNDr. Antalíková Jana PhD.
Annotation: Fertilization in mammals is complicated and a complex process, which includes amount of molecules on oocytesand sperm. Their identification is not complete yet, and their function and cooperation is not understood. The aimof the proposed project is to study tetraspanins (focusing on CD9, CD81 molecules) and their partner moleculeswithin the multi-molecular "tetraspanin web" on oocytes and sperm of cattle. Using monoclonal antibodies, thebiochemical and immunochemical analysis will be performed and study of the role of this molecule inreproduction-related processes using in vitro fertilization experiments will be performed.
Duration: 1.1.2016 – 31.12.2019
Úloha lipidových partikúl v biotechnologickej produkcii skvalénu kvasinkami
The role of lipid droplets in the biotechnology of squalene production in yeast
Program: VEGA
Project leader: RNDr. Hapala Ivan CSc.
Annotation: Lipid droplets are dynamic organelles participating in the accumulation of neutral lipids as energy source or stores of simple lipid components for membrane biogenesis. The project is aimed at the role of yest lipid droplets in the accumulation of a high-value lipid squalene. Squalene is produced as the precursor in sterol biosynthesis and due to its physico-chemical properties it finds broad applications in food industry, cosmetics and pharmacology.Limited natural resources open the way for yeast as an alternative organism for squalene production. Genetic modification of squalene epoxidase (Erg1p) will be used in the project to increase squalene levels in yeast. The main aim of the project will be the identification of facors affecting the storage capacity of lipid droplets for squalene (genes affecting lipid droplet biogenesis,lipid and protein composition)and the potential lipotoxicity of squalene if the storage capacity of lipid droplets is exceeded.
Duration: 1.1.2016 – 31.12.2019
BIOGLYCO – Biočipy a biosenzory pre glykorozpoznávanie, ich vývoj, príprava a využitie pri výskume rakoviny
Biochips and biosensors for glycorecognition, their development, prepararion and application in cancer research
Program: APVV
Project leader: Ing. Sulová Zdena DrSc.
Annotation: Due to the rapid development of new technologies is placed a considerable emphasis on their use for improving the quality of life. The most important areas here include the care of human health, such as the fight against cancer. Here is a keen interest in new sensitive diagnostic approaches and technologies to help increase theeffectiveness of therapy and cancer research. Development and application of new diagnostic procedures andmethods is based in no small measure on the knowledge gained in the basic research in the field of analyticaltools based on the biochips and biosensors. The aim of the project is the development and preparation of new analytical glyco-recognizing biochip and biosensor systems based on lectin in different formats in combination with multiple platforms and innovative detection methods, their validation and use in the analysis of real samplesin cancer research. The selected design of biochips and used detection platform enable highly sensitive and high-throughput analysis of glycosylation changes, and the involvement of mass spectrometry also accurate identification of glycan structures subject to glycosylation changes. To increase the functionality of biochips will be in the development of analytical systems used also nanotechnology tools, particularly in the preparation of nanostructured surfaces of biochips and for improving the efficiency of detection. Various types of biological samples will be analyzed such as serum, lysates, tissue and isolated glycoproteins from some areas of cancer research (effect of hypoxia, resistance to cytostatics, search of glyco-biomarkers). It is expected that theinvolvement of the entire spectrum of analytical procedures for glycorecognition developed in this project will help formulate more sophisticated conclusions on the role of glycans in cancer.
Duration: 1.7.2015 – 30.6.2019
CAMYS – Cytoarchitektúra vápnikovej signalizácie srdcových myocytov vo vývoji hypertrofie myokardu
Cytoarchitecture of calcium signalling of cardiac myocytes in development of myocardial hypertrophy
Program: APVV
Project leader: Ing. Zahradníková Alexandra DrSc.
Annotation: In early phases of many cardiovascular diseases, calcium signalling deteriorates and cardiomyocyte hypertrophy is activated. Calcium signalling, in addition to control of contractile function, modulates many of signalling pathways and metabolism of myocytes. Therefore, disruption of calcium signalling in either systolic or diastolic phase may be a consequence, but also the cause of the maladaptive reaction of myocytes to overload. We hypothesize that processes related to hypertrophy lead to changes in distribution of endo/sarcoplasmic reticulum elements responsible for calcium signalling and for proteosynthesis, and to associated changes in expression and distribution of calcium signalling proteins. This study aims to determine differences in the myocyte calcium signalling system of myocardium adapting to pathological or physiological load and to compare them with development of the myocyte calcium signalling system during postnatal maturation of myocardium. The status of the calcium signalling system will be analysed in models of myocardial load in laboratory rats: a/ sedentary model – animals in standard cages, b/ model of physiological load – animals in cages with a running wheel, 3/ model of pressure overload – surgical obstruction of ascending aorta, and d/ growth model of hypertrophy – postnatal development of myocardium. State-of-the-art methods of electrophysiology, molecular biology and ultrastructural microscopy will be used to characterize quality and distribution of calcium signals, the extent and distribution of smooth and rough sarcoplasmic reticulum, and of expression, localization and co-localization of calcium signalling proteins. We expect that the multidisciplinary approach supported by the expertise of team members will allow interpreting cellular and molecular mechanisms of calcium signalling and drawing conclusions relevant to understanding mechanisms of heart failure that will aid development of new therapeutic and preventative procedures.
Project web page: http://www.umfg.sav.sk/ovsb/projektyovsb/aktivne-projekty-v-ovsb/apvv-15-0302/
Duration: 1.7.2016 – 30.6.2019
APTADIAG – Vývoj progresívnej diagnostickej metódy pre klinickú onkológiu založenej na interakcii DNA aptamérov s proteínmi
Development of novel diagnostic method for clinical oncology based on the interaction of DNA aptamers with proteins
Program: APVV
Project leader: Ing. Poturnayová Alexandra PhD.
Annotation: The project is focused on the development of novel diagnostic method for clinical oncology based on theinteraction of DNA aptamers with membrane proteins. For this purpose the extensive basic research will beperformed with focus on the study of the mechanisms of interaction DNA aptamers with model proteinsincorporated into the supported lipid membranes as well as with tumor markers at the surface of the cell cultures.The progressive biophysical methods will be applied such as acoustic thickness shear mode method, atomicforce misroscopy, single molecule force spectroscopy, fluorescence resonance energy transfer and others. Theexprienced teams composed of senior scientists, young researchers and PhD students from Faculty ofMathematics, Physics and Informatics of Comenius University in Bratislava and from two Research Institutes ofthe Slovak Academy of Sciences – Institute of Animal Biochemistry and Genetics and Cancer Research Institutewill be involved in the project. We assume that will obtain new knowledge on the mechanisms of interaction ofDNA aptamers with membrane proteins depending on the lipid composition as well as with tumor markers at thesurface of cell cultures depending on the type of the tumor and the progress of dissease.
Duration: 1.7.2015 – 30.6.2019
Dynamika a morfológia mitochondrií u transgénneho modelu Wolframovho syndrómu: význam pre ochranu srdca
Mitochondrial dynamics and morphology in transgenic model of Wolfram syndrome: emerging role for heart protection
Program: VEGA
Project leader: RNDr. Cagalinec Michal PhD.
Annotation: Wolfram syndrome (WS) is a recessive neurological disorder caused by mutation of the Wfs1 gene. The Wfs1 protein is highly expressed in the brain and heart and is embedded in the endoplasmic reticulum (ER) where it modulates Ca2+ levels and ER stress. Additionally, the main symptoms of the WS are consistent with the ones characteristic for mitochondrial diseases. In fact, our preliminary results showed already that silencing of Wfs1 in mouse neurons decreased the mitochondrial fusion frequency and caused mitochondrial fragmentation, demonstrating strong impact of Wfs1 to mitochondrial function in neurons. Although the high expression of Wfs1 in the heart and cardiac symptoms in WS identified recently emphasize the functional importance of Wfs1 in the heart, the most common causes of morbidity in WS are the neurological manifestations.
Duration: 1.1.2016 – 31.12.2018
Funkčné prepojenie mitochondrií a endoplazmatického retikula u Wolframovho syndrómu: predpokladaný význam pre ochranu mozgu a srdca
Mitochondria-endoplasmic reticulum functional interplay in Wolfram Syndrome: emerging role for heart and brain protection
Program: SASPRO
Project leader: RNDr. Cagalinec Michal PhD.
Project web page: http://www.confolab.sav.sk/indexSASPRO.html
Duration: 1.3.2015 – 31.12.2018
Kvasinkové fosfatidylinozitol transferové proteíny: homeostáza lipidov a rezistencia k azolovým antimykotikám
Yeast phosphatidylinositol transfer proteins: lipid homeostasis and resistance to azole antimycotics.
Program: VEGA
Project leader: RNDr. Griač Peter CSc.
Annotation: Phosphatidylinositol transfer proteins (PITPs) were found in all eukaryotic organisms where studied. PITPs inmammals are involved in multiple important metabolic pathways and in transmission of nerve signals. In yeaststhey form a heterogenous group with different sub-cellular localizations and multiple, mostly unknown, roles in cellphysiology. One of these proteins, Pdr16, is involved in the development of yeast resistance to azoleantimycotics. The other one, Sfh1p, is supposed to play role in sphingolipid biosynthesis and intracellularsignaling. The present project aims to investigate the mechanisms by which PITPs are involved in maintainingoptimal lipid composition of eukaryotic cell membranes and their role in the development of azole resistance.Basic knowledge will be obtained using the model organism, yeast Saccharomyces cerevisiae. Our findings willbe applied to study PITPs relationship to azole resistance in the opportunistic pathogen Candida albicans.
Duration: 1.1.2015 – 31.12.2018
Nové spôsoby regulácie N-typu (CaV2.2) vápnikových kanálov
Novel pathways of N-type (CaV2.2) calcium channels regulation
Program: VEGA
Project leader: doc. RNDr. Lacinová Ľubica DrSc.
Annotation: Neurotransmission controlled by CaV2.2 or N-type calcium channels plays a major role in chronic andneuropathic pain which is a major clinical, social and economic problem. Ziconotide is the only one drugspecifically targeting CaV2.2 channel. It is delivered intrathecally leaving demand for an oral drug open. Ionchannels form macromolecular signaling complexes with a variety of interacting proteins and stabilization ordisruption of such interactions may be a base for a novel therapeutic strategy. Modified yeast-two-hybrid assayidentified proteins RTN1, SLC38A1, Ptgds, TMEM 223, and Grina as putative interaction partners of the CaV2.2channels. These proteins are expressed predominantly or solely in neurons and several neuromodulatoryfunctions of these proteins were described. We hypothesize that they may modulate CaV2.2 channels, as well.Our aim is to describe functional mechanisms and/or intracellular pathways involved in the interaction betweenCaV2.2 channels and listed interacting proteins.
Duration: 1.1.2016 – 31.12.2018
Vplyv látok vyvolávajúcich stres endoplazmatického retikula a inhibítorov proteozómu na leukemické bunkové línie L1210, SKM-1 a MOLM-13, u ktorých bola vyvolaná nadexpresia P-glykoproteínu
The effect of endoplasmic reticulum stress inductors and proteaosome inhibitors on leukemia cell line L1210, SKM-1 and MOLM-13 with induced P-glycoprotein overexpression
Program: VEGA
Project leader: Mgr. Šereš Mário PhD.
Annotation: The leukemia mouse cells L1210 in which was induced the P-glycoprotein (P-gp) expression of either by selection with vincristine or transfection with the P-gp encoding gene. We have found that cells with P-gp overexpression, have developed resistance not only to substrates of P-gp, but also to cisplatin (antineoplastic agent, which is not P-gp substrate) and endoplasmic reticulum (ER) stress inducing substances. Further, we observed significant differences in interaction with lectins, between P-gp positive and P-gp negative L1210 cells, indicating extensive remodeling of surface carbohydrates, associated with the P-gp expression in these cells. The presence of P-gp in leukemia cells induces large changes of cell regulatory processes involving protein phosphorylations and glycosylations and the regulation of the apoptosis progression. New knowledge of P-gp regulatory role may contribute to a better understanding of the P-gp mediated multidrug resistant mechanism of leukemia cells to cytostatics.
Duration: 1.1.2016 – 31.12.2018
Zmeny citlivosti leukemických buniek na chemoterapeutiká vyvolané zmeneným expresným profilom membránových transportérov.
Changes of leukemia cells drug sensitivity induced by changes of membrane drug transporters expression profile.
Program: VEGA
Project leader: doc. Ing. Breier Albert DrSc.
Annotation: Multidrug resistance (MDR) of neoplastic cells represents real obstacle in chemotherapy of cancer diseases.Expression of P-glycoprotein (P-gp), a plasma membrane drug transporter represents most often occurredmolecular cause of MDR. Several cell processes and regulatory pathways including protein glycosylation andphosphorylation are involved in P-gp mediated MDR development. Study of multi-player cellular mechanisms thatmay alter regulation of P-gp expression, degradation and transport activity represents highly important topic forintensive research activity. This research has potential to bring data applicable for enlargement of targetedtherapeutic protocols effective for concrete type of neoplastic disease of respective individuals with multidrugresistance mediated by P-gp. The project will be focused on hematological malignancies predominantly onleukemia using different human and animal cell models.
Duration: 1.1.2015 – 31.12.2018
Možná duálna funkcia P-glykoproteínu pri viacliekovej rezistencii leukemických buniek: efluxná pumpa a regulačný proteín
Possible dual function of P-glycoprotein in leukemia cells: efflux pump and regulatory protein
Program: APVV
Project leader: Ing. Sulová Zdena DrSc.
Annotation: Project is focused on hypothesis that P-glycoprotein besides its generally accepted role as multidrug efflux pump for large groups of lipophilic substances also play additional role as regulatory protein influencing programmed cell death progression. Several lines of evidences indicated, that this regulatory action of P-gp is independent on P-gp transport activity. Therefore, P-gp when express in cells, could depress cell sensitivity also to substances which cannot be effluxed by its transport activity. We studied this trend on mice leukemia cells L1210 in which the P-gp expression was induced either by selection for resistance with vincristine, or by transfection with gene encoding full length P-gp. We found that P-gp overexpressing cells are resistant also to endoplasmic reticulum stressors like tunicamycin (inhibitor of N-glycosylation in endoplasmic reticulum), thapsigargin (inhibitor of Ca (2+)-ATPase from endoplasmic reticulum); but also to cisplatin (chemotherapeutic that is not substrate for P-gp), and lastly to lectin Concanavalin A. However P-gp positive cells were more sensitive than their P-gp negative counterparts to another lectin from wheat germ. These results are associated with massive remodalation of cell surface saccharides in cells with upregulated P-gp. Presence of P-gp in cells seems to induce strong alteration in cell regulatory pathways including either protein phosphorylation and glycosylation or regulation of apoptosis progression. These issues we plane to study by described P-gp cell models, or by using the human leukemia cells, in which the P-gp overexpresion was induced by adaptation with chemotherapeutics like vincristine, mitoxantrone or azacytidine.
Duration: 1.7.2015 – 31.7.2018
SPMEIOSIS – Charakterizácia nových génov potrebných pre meiotickú segregáciu chromozómov.
Characterization of novel genes involved in meiotic chromosome segregation.
Program: SASPRO
Project leader: Mgr. Bágeľová Poláková Silvia PhD.
Project web page: http://www.saspro.sav.sk/
Duration: 1.4.2015 – 31.3.2018
Expresia a kolokalizácia proteínov diadických komplexov komorových myocytov potkana vo vzťahu k ontogenéze väzby excitácie s kontrakciou.
Expression and co-localization of dyadic protein complexes in ventricular myocytes in relation to excitation-contraction coupling ontogenesis.
Program: VEGA
Project leader: RNDr. Zahradníková, ml. Alexandra PhD.
Annotation: Excitation-contraction coupling in ventricular myocytes is based on calcium signalling in dyads – specialized junctions of sarcolemma and terminal cisternae of sarcoplasmic reticulum. The relationship between the molecular structure of dyads and the functionality of calcium signalling is not sufficiently understood, since its direct experimental manipulation is not possible. It should be possible to observe correlation between the structure and function of dyads during the postnatal stage of cardiac development, a period of their extensive formation and growth. The aim of the project is to correlate the changes in local calcium signalling to protein composition and interaction in individual dyadic complexes during myocyte ontogenesis. The acquired data will allow us to formulate hypotheses about the relationship between the structure and function of dyads at the molecular level and will help us understand the adaptive processes, occurring during cardiac hypertrophy, at the level of calcium signaling.
Duration: 1.1.2015 – 31.12.2017
Chorioalantoická membrána embrya prepelice japonskej ako in vivo model na testovanie hypericínom indukovanej fluorescenčnej diagnostiky nádorových lézií
Japanese quail chorioallantoic membrane as in vivo model for testing hypericin induced fluorescence diagnosis of tumor lesions
Program: VEGA
Project leader: RNDr. Bilčík Boris PhD.
Annotation: Cancer of the oral cavity is one of the most common forms of malignancy, with rather poor survival. Early diagnosis and precise localization is crucial, however, oral tumors are mostly superficial and its margins can be difficult to visualize under white light. Promising approach is photodynamic diagnosis (or drug induced fluorescence imaging). The aim of our proposal is to evaluate model for diagnosis and treatment of squamocellular carcinoma using quail chorioallantoic membrane (CAM) and a plant-based photosensitiser hypericin (Hyp). The combination of high-resolution fluorescence imaging systems and image analysis will enable more precise visualization of the tumor margins and differentiate tumors, pre-cancerous and inflammatory tissues.
Duration: 1.1.2015 – 31.12.2017
Regenerácia špecifických regiónov mozgu dospelých spevavcov skúmaná pomocou in vivo magnetickej rezonancie
Regeneration of specific brain regions of adult songbirds studied by in vivo magnetic resonance
Program: VEGA
Project leader: Mgr. Niederová Ľubica PhD.
Annotation: Neurodegenerative diseases represent a major problem recently because their occurrence rises with increasing age of human population. Neurogenesis, generation of new neurons, is intensively studied for treatment of neurodegeneration. The rate of neuronal regeneration can be influenced also by dopamine receptors (DRs) activity. However, the precise mechanism how DRs affect generation of new neurons after brain damage is unclear. The aim of this project is to study the mechanism and to investigate the rate of this regeneration using invivo magnetic resonance – MRI. We will use a model of songbirds which learn their songs from other birds and the song learning and production are controlled by specialized brain areas. We will damage a specific striatal region important for song learning. This injury and the following regeneration will provide the advantage of preciseexaminantion of behavioral subsequences of both processes. Our results should add to understanding the brain regeneration mechanism after injury.
Duration: 1.1.2014 – 31.12.2017
Štúdium mitochondriálnych lipidov v kvasinkách Saccharomyces cerevisiae a Schizosaccharomyces pombe.
Study of mitochondrial lipids in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe.
Program: VEGA
Project leader: Mgr. Balážová Mária PhD.
Annotation: Optimal membranes lipid composition is essential for their function and the proper functioning of the cell. The maintenance of biomembranes lipid composition is a dynamic process involving lipid synthesis, degradation, transport, and remodeling. Aim of the project is to study mitochondrial phospholipids in two yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe. Mitochondrial membranes contain specific anionic phospholipid, cardiolipin (CL) and its precursor, phosphatidylglycerol (PG). The project is oriented to the study of regulatory mechanisms involved in CL biosynthesis. In the yeast S. cerevisiae the experiments will be aimed to understand the function of PG specific phospholipase C, Pgc1p. In Sch. pombe we plan to identify and analyze CL synthase. Using the comparative analysis of novel regulatory mechanisms of the CL biosynthetic pathway we will contribute to the understanding of the mechanisms by which eukaryotic cells sustain the optimal lipid composition of mitochondrial membranes.
Duration: 1.1.2014 – 31.12.2017
Účinok stresu vyvolaného imunitnou reakciou počas gravidity potkanov na následnú starostlivosť o mláďatá a na hipokampálnu excitabilitu mláďat.
Effects of stress, induced by immune challenge during the gestation in rats, on maternal care behaviour and on hippocampal neuronal excitability in the offsprings
Program: VEGA
Project leader: MMedSc Dremencov Eliyahu PhD
Annotation: There is evidence that children of women which experienced stressful conditions during the pregnancy have higher risk to develop certain brain disorders, such as depression, schizophrenia, and autism. One of the common stressors experienced by pregnant women is acute infective illness. Little is known how prenatal infection influences the functioning of offspring brain. In this study, we plan to investigate the effect of prenatal immune challenge resembling infective illness, on maternal care behaviour of laboratory rats and on hippocampal neuronal activity of their pups. The immune challenge will be induced by the administration of bacterial endotoxin lipopolysaccharide (LPS). Neuronal excitability will be examined in hippocampus, the structure related to depression, schizophrenia and autism, and compared between offsprings of rats treated with LPS and control rats. The results generated by this project will provide better understanding of pathophysiology of brain disorders triggered by prenatal stress.
Duration: 1.1.2015 – 31.12.2017
Úloha fyziologicky aktívnych iónov Mg2+ a Zn2+ v luminálnej regulácii srdcového ryanodínového receptora.
The role of physiologically relevant metal ions Mg2+ and Zn2+ in the luminal regulation of the cardiac ryanodine receptor.
Program: VEGA
Project leader: Mgr. Gaburjáková Jana PhD.
Annotation: The key determinant of cardiac contractility is Ca2+ released from the sarcoplasmic reticulum (SR) via the ryanodine receptor type 2 (RYR2). The major regulation domain of the RYR2 channel is a huge cytosolic head. Smaller luminal domain also contributes to the channel regulation, and importantly, its dysfunction leads to generation of specific ventricular arrhythmias. The main luminal regulator of the RYR2 channel is Ca2+. However, other cations such as Mg2+ and Zn2+ are also present in the SR and can contribute to the luminal regulation by binding to luminal RYR2 sites. These binding sites are localized either on the channel protein or on the associated protein-calsequestrin (CSQ2). Our aim is to examine the luminal regulation of the RYR2 channel in more comprehensive manner in respect to cationic composition of the luminal environment. On the single channel level we will examine the role of Mg2+ and Zn2+ in luminal regulation of the RYR2 channel at diastolic (1 mM) or systolic (0.6 mM) luminal Ca2+. Outcomes of experiments will be correlated to the CSQ2 presence in the RYR2 protein complex.
Duration: 1.1.2015 – 31.12.2017
ER stres – myo – Vplyv stresu endoplazmatického retikula na ultraštruktúru a metabolizmus kardiomyocytov cicavcov
Effect of endoplasmic reticulum stress on ultrastructure and metabolism of mammalian cardiomyocytes
Program: APVV
Project leader: RNDr. Novotová Marta CSc.
Annotation: Endoplasmic reticulum (ER) stress has been implicated in many cardiovascular diseases. Currently, the research on ER stress is aimed toward preservation of the beneficial adaptational response and elimination of the deleterious apoptosis in disease. The objective of this project is to study the adaptational changes in the cytoarchitecture of cardiomyocytes under ER stress, with focus on both, the smooth and rough forms of the reticular membrane system. We will characterize remodeling of myocyte cytoarchitecture induced by application of tunicamycine (the reticular stressor) in control mice and in mice with knocked-out sirtuin1 gene (SIRT1 ciKO mice). Sirtuin1 is a general metabolic energy sensor activated in response to cellular stress that protects cells from apoptosis. We hypothesize that SIRT1 may regulate the unfolded protein response and protect the heart against ER stress-induced damages.
Duration: 1.1.2016 – 31.12.2017
Vplyv záťaže myokardu na distribúciu vnútorného membránového systému srdcových myocytov
The effect of myocardial load on distribution of the endoplasmic membrane reticulum of cardiac myocytes
Program: VEGA
Project leader: RNDr. Novotová Marta CSc.
Annotation: In our previous studies, we have shown that cytoarchitecture contributes to intracellular signaling in cardiac myocytes and that cytoarchitectual changes accompany cardiac remodeling. This project aims at characterization of the morphological variability of the sarcolemma and of the sarcoplasmic reticulum with emphasis on the local aspects of excitation-contraction coupling. Changes in the spatial relations of the plasma membrane and of membranes of the sarcoplasmic reticulum will be studied in the mammalian myocardium with the aim to classify and quantify their structural dynamics in the physiologically and pathologically loaded myocardium. Comprehension of the plasticity of the membrane system will be instrumental in understanding of the membrane morphology as the adaptability factor in cardiac myocytes.
Project web page: http://www.confolab.sav.sk/indexVEGMN.html
Duration: 1.1.2015 – 31.12.2017
Úloha neurosekrečných neurónov a vápnikovej signalizácie v depresii a návykovom správaní: hodnotenie prostredníctvom in-vivo elektrofyziológie (Štipendium SAV)
Role of Neurosecretory Neurons and Calcium Signalling in Depression and Addictive Behaviour: Assessment by in-vivo Electrophysiology (SAS Scholarship Program)
Program: Iné projekty
Project leader: MMedSc Dremencov Eliyahu PhD
Duration: 8.10.2013 – 7.10.2017
Emócie, kognitívne procesy a welfare hydiny
Emotions, cognition and poultry welfare
Program: VEGA
Project leader: RNDr. Košťál Ľubor CSc.
Annotation: Relations between emotions and cognition are currently intensively studied from the perspective of differentscientific disciplines, including animal welfare science. The aim of this project is to contribute to the developmentof techniques for the study of poultry welfare. In field of methods using cognitive abilities to assess affectivestates (emotions), we will focus in our project on the development of methods using touch-screen operantchambers. This approach will allow us to the follow affect-induced judgement bias caused by differentenvironmental conditions. In the area of facial expression of emotions under behaviorally defined conditionscorresponding to basic emotions, we will use computerized image analysis techniques to test hypothesis whetherbirds have facial expression of emotions. Under similar controlled conditions we will be using thermal imaging tocompare the temperature of comb, wattles and eye, as potential physiological indicators of emotional states inlaying hens.
Duration: 1.1.2014 – 31.12.2016
Príjem sterolov ako adaptačný mechanizmus kvasiniek na nepriaznivé podmienky.
Sterol uptake. An adaptation mechanism to hostile conditions in yeast.
Program: VEGA
Project leader: Mgr. Valachovič Martin PhD.
Annotation: The proposed project addresses utilization of exogenous sterols in yeast as possible adaptation to hostile conditions (anaerobiosis, treatment with antifungals targeted on ergosterol synthesis). It will primarily focus on the plasma membrane ATP-binding cassette (ABC) proteins implicated in sterol import in the model organism Saccharomyces cerevisiae. Active involvement of cell wall in sterol uptake will be investigated and novel components or alternative pathways of external sterol utilization will be sought on the whole-genome level. Since pathogenic fungi experience often hypoxic environment, anaerobic adaptations in the sterol uptake pathway (cell wall and putative sterol importers) are of special interest. Information acquired in this project will broaden the general knowledge about sterol utilization and functions of ABC transporters. The results will be potentially applicable in the antimycotic treatment of some pathogenic fungi and will eventually define novel targets for antifungals.
Duration: 1.1.2014 – 31.12.2016
Úloha kalsequestrínu v luminálnej regulácii ryanodínového receptora v srdci
The role of calsequestrin in luminal regulation of the cardiac ryanodine receptor
Program: VEGA
Project leader: Mgr. Gaburjáková Marta PhD.
Annotation: In cardiac muscle, the contraction is initiated by a massive Ca2+ release from the sarcoplasmic reticulum (SR) cisternae via activated ryanodine receptors (RYR2) functioning as Ca2+ channels. The major physiological activator of the RYR2 channel is Ca2+ that binds to its large cytosolic domain. However, there is growing evidence that the Ca2+ binding to a minor luminal region of the RYR2 channel can also be effectively involved in the channel regulation. Several studies indicate that calsequestrin (CSQ2) as the main Ca2+-binding protein in the SR lumen could play the role of a luminal Ca2+ sensor of the RYR2 channel. The aim of our work is to clarify the role of CSQ2 in the luminal regulation of the RYR2 channel by combination of electrophysiological and biochemical methods. This interdisciplinary approach is expected to contribute to the detail understanding of the functional communication between CSQ2 and the RYR2 channel from the biophysical as well as the physiological point of view.
Project web page: http://www.umfg.sav.sk/obfg/projekty/aktivne-projekty/vega-2000314/
Duration: 1.1.2014 – 31.12.2016
Viaclieková rezistencia leukemických buniek na rôzne terapeutiká
Multidrug resistance of leukemia cells to diverse drugs
Program: VEGA
Project leader: Ing. Sulová Zdena DrSc.
Duration: 1.1.2013 – 31.12.2016
Vývoj diadickej vápnikovej signalizácie v priebehu postnatálneho vývoja ventrikulárnych myocytov.
Development of dyadic calcium signaling during postnatal maturation of ventricular myocytes.
Program: VEGA
Project leader: RNDr. Zahradník Ivan CSc.
Annotation: Cardiac muscle of new-borns develops in concert with the development of physical activity. In cardiac myocytes, the volume of contractile myofibrils, of inner membrane system and of mitochondria increases. Circulation of calcium ions during the contraction-relaxation cycle becomes progressively internalized, and the dyadic system that serves for excitation-contraction coupling by means of calcium signalling expands. The objective of the project is to characterize the development of calcium release and of ultrastructure of the dyads during postnatal development of rat myocardium. Original data on the development of calcium signalling, acquired in isolated cardiac myocytes by laser scanning confocal microscopy combined with the patch clamp method, will be correlated with data on development of dyadic ultrastructure acquired by means of electron microscopy. The results will aid clarification of calcium signalling in the cardiomyocytes of neonatal heart.
Project web page: http://www.umfg.sav.sk/ovsb/projektyovsb/aktivne-projekty-v-ovsb/vega-2014714/
Duration: 1.1.2014 – 31.12.2016
Vzťahy medzi štruktúrou a funkciou ryanodínového receptora
Structure-function relationships of the ryanodine receptor
Program: VEGA
Project leader: Ing. Zahradníková Alexandra DrSc.
Annotation: Correct functioning of ryanodine receptors (RyRs) is crucial for proper myocardial function. Ryanodine receptors maintain calcium homeostasis by regulation of diastolic calcium leak, and ensure proper extent of contraction by regulation of calcium-induced calcium release during the systole. In civilization diseases of the heart and in some inherited arrhythmias, RyR function is disturbed as a result changed phosphorylation, redox state, or RyR mutations, which leads to decreased contraction and increase of diastolic calcium release. The structure-function relationships of RyR from the viewpoint of regulation of its activity are not well understood. In this project we will focus on deciphering modulation of RyR activity at the level of single channels, dyadic channel complexes, and isolated cardiac myocytes. The results will enable deeper understanding of the mechanisms that govern RyR activity during systole and diastole.
Project web page: http://www.umfg.sav.sk/ovsb/projektyovsb/aktivne-projekty-v-ovsb/vega-2014814/
Duration: 1.1.2014 – 31.12.2016
Štúdium mechanizmov interakcie DNA aptamérov s rakovinovými markermi na povrchu leukemických T-buniek
The study of the mechaisms of interaction DNA aptamers with cancer markers at the surface of leukemic T-cells
Program: VEGA
Project leader: Ing. Poturnayová Alexandra PhD.
Annotation: Project is focused on development new methods for cancer diagnosis based on atomic force spectroscopy (AFM) using DNA aptamers specific to the cancer cells in the membranes of the leukemic T-cells. DNA aptamers specific to cancer marker will be immobilized at the AFM tip and the specific interaction with the cancer markers at the surface of leukemia T-Cells will be determined by atomic force spectroscopy or by means of thickness shear mode acoustic methods (TSM). Research will focus on the systematic study of the use of DNA aptamers in the diagnosis of cancer, the analysis of specific and non-specific interaction with the surface of the T-cells and to study their topography. These interactions will be monitored in real time and allow the determination of kinetic binding constants. We expect, that using DNA aptamers and AFM we will able to distinguish normal and pathological cells and propose a new, efficient method early diagnosis of cancer.
Duration: 1.1.2014 – 30.12.2016
Dobudovanie infraštruktúry pre moderný výskum civilizačných ochorení
Program: Štrukturálne fondy EÚ Výskum a vývoj
Project leader: Ing. Sulová Zdena DrSc.
Duration: 8.10.2015 – 31.12.2015
Indukcia apoptózy cez moduláciu IP3 receptorov v nádorových bunkách
Program: VEGA
Project leader: prof. Ing. Križanová Oľga DrSc.
Duration: 1.1.2013 – 31.12.2015
IP3 receptory, ich modulácia a funkcia v nádorových bunkách
IP3 receptors, their modulation andf function in cancer cells
Program: APVV
Project leader: prof. Ing. Križanová Oľga DrSc.
Duration: 1.7.2012 – 31.12.2015
lipotox – Lipotoxicita u kvasiniek: mechanizmy ochrany pri akumulácii mastných kyselín a skvalénu.
Lipotoxicity in yeast: mechanisms of protection against accumulated fatty acids and squalene.
Program: APVV
Project leader: Mgr. Holič Roman PhD.
Annotation: The basic research project is aimed at the mechanisms of cellular protection from lipotoxic effect of two lipophilic substances varied in structure and origin – squalene and ricinoleic acid. Squalene is an isoprenoid produced in yeast as a precursor in the ergosterol biosynthetic pathway. Ricinoleic acid is an unsaturated hydroxy fatty acid that will be produced in yeast after heterologous expression of a foreign gene encoding the enzyme hydroxylase. Using a broad spectrum of biochemical, genetic and genomic methods we will focus on two mechanisms of cellular protection from lipotoxic substances – increased storage capacity of yeast cell by stimulation of lipid particle biogenesis and secretion as a novel mechanism of lipid detoxification. Obtained knowledge will help to explain mechanisms of squalene and ricinoleic acid lipotoxicity in yeast as well as the general mechanisms how eukaryotic cells (including human ones) protect themselves from the toxic effect of lipids. The results may be also applied for increase of the production of these two industrially important lipids in yeast.
Duration: 1.7.2012 – 31.12.2015
Molekulárne mechanizmy spolupôsobenia stresových hormónov a hypoxie v nádorových bunkách: vplyv na expresiu a funkciu nádorového proteínu CA IX
Program: APVV
Project leader: prof. Ing. Križanová Oľga DrSc.
Duration: 1.7.2012 – 31.12.2015
Princíp vrátkovania napäťovo závislých vápnikových kanálov
Principle of gating of voltage-dependent calcium channels
Program: VEGA
Project leader: doc. RNDr. Lacinová Ľubica DrSc.
Annotation: Change of transmembrane voltage initiates activation, deactivation and inactivation of voltage-dependent ion channels including voltage-dependent calcium channels. This so-called gating precisely regulates entry of calcium ions into the cell. In addition to electrical excitability intracellular calcium ions control number of processes including secretion, contraction and gene transcription. How precisely gating machinery of an voltage-dependent channel turns change of transmembrane voltage into conformational changes of channel’s voltage sensor and conducting pore is not know. We will address function of voltage sensors in individual domains of CaV3 voltage-dependent calcium channel and the interaction of these sensors with channel’s conducting pore with the aim to identify determinants of activation threshold voltage.
Duration: 1.1.2013 – 31.12.2015
Príprava nanoštruktúrovaných filmov, ich integrácia s bioelementmi a následné využitie
Preparation of nanostructured interfaces, their integration with bioelements and subsequent use
Program: APVV
Project leader: Ing. Sulová Zdena DrSc.
Duration: 1.7.2012 – 31.12.2015
Protinádorový účinok biologicky aktívnych ligandov heterodimérov nukleárnych retinoidných X receptorov v tkanivových kultúrach
Antitumour effect of biologically active ligands of nuclear retinoid X receptor heterodimers in tissue carcinoma cell lines
Program: APVV
Project leader: Ing. Sulová Zdena DrSc.
Duration: 1.7.2012 – 31.12.2015
Sekrécia mastných kyselín u kvasiniek Saccharomyces cerevisiae
Fatty acid secretion in the yeast Saccharomyces cerevisiae
Program: VEGA
Project leader: Mgr. Holič Roman PhD.
Annotation: The proposed project is oriented towards the study of mechanisms of fatty acids secretion and uptake in the yeast Saccharomyces cerevisiae. Using the whole genome analyses genes participating in the control mechanisms of fatty acids secretion will be identified. The mechanisms of fatty acids secretion in yeast is largely unknown. Available data indicate that mechanism of fatty acids secretion is tightly bound to the uptake of external fatty acids. It is therefore expected that in the course of the whole genome analyses of fatty acids excretion, also genes regulating uptake of external fatty acids will be identified. Obtained results may help to better understand the mechanisms of cellular defence mechanisms against lipotoxicity. The results will be applicable also in biotechnology in the heterologous production of important fatty acids.
Duration: 1.1.2012 – 31.12.2015
Signálna dráha oxidu dusnatého a sírovodíka, jej poruchy a podiel na vzniku hypertenzie a aterosklerózy
Signaling pathway of nitric oxide and hydrogen sulfide, their perturbation and contribution on hypertension and atherosclerosis
Program: Iné projekty
Project leader: RNDr. Ondriaš Karol DrSc.
Annotation:
Duration: 19.7.2013 – 31.12.2015
H2S – Štúdium molekulárnych mechanizmov biologických účinkov H2S
Study of molecular mechanism of H2S biological effects
Program: APVV
Project leader: RNDr. Ondriaš Karol DrSc.
Duration: 1.7.2012 – 31.12.2015
Štúdium molekulárnych mechanizmov sprostredkujúcich účinky ionofórov na membránové kompartmenty eukaryotickej bunky
Molecular mechanisms mediating the effect of ionophores on membrane compartments of eukaryotic cells
Program: VEGA
Project leader: RNDr. Griač Peter CSc.
Annotation: Cellular compartments represent a dynamic system that constantly evaluates the changes in the environment. The long-term goal of our laboratory is a detailed description of mechanisms contributing to regulation and execution of cellular responses to fluctuations in ion homeostasis induced by ionophores. Based upon the results obtained within the frame of the previous project financed by VEGA, we plan (i) to perform functional analysis of those genes in Saccharomyces cerevisiae, whose absence leads to changes in sensitivity of the mutant cells toionohores, (ii) to analyze the effects of ionophores on the yeast Schizosaccharomyces pombe, and (iii) to analyze the effects of ionophores on stability of mitochondrial nucleoids. The results of the proposed project will help us to get closer to our ultimate goal, which is better understanding of molecular principles enabling coordinated cellularresponses to perturbed ion homeostasis.
Duration: 1.1.2012 – 31.12.2015
Štúdium tkanivovej distribúcie, biochemických vlastností a funkcie CD molekúl v reprodukčnom procese hovädzieho dobytka.
The study of tissue distribution, biochemical properties and functions of CD molecules in the reproductive process of cattle.
Program: VEGA
Project leader: RNDr. Antalíková Jana PhD.
Annotation: A part of the fertilization process in mammals is a cell adhesion of gametes, in which some of the CD molecules play a role. Most of them are glycoproteins with various functions in the immune system; some of CD molecules are present on gametes. The aim the proposed project is to study the expression and the localization of CD molecules on cattle gametes and tissues, with focusing on the analysis of CD9 molecule, forming complexes with other molecules within the ”tetraspanin web”, identification of its partner molecules and their participation in the process of fertilization. Using monoclonal antibodies against the bull sperm, the cytometric, histochemical and biochemical analysis will be performed. A detailed biochemical and functional analysis of the CD46 and CD52 in the gametes and embryos of the cattle using the mAbs IVA-520 and IVA-543 and the study of the changes in their expression and modification during the process of the sperm epidydimal maturation, capacitation and acrosome reaction will be made.
Duration: 1.1.2012 – 31.12.2015
Úloha Na/Ca výmenníka pri nádorových ochoreniach, potenciálna modulácia vybranými transmitermi.
Role of the Na/Ca exchanger in tumor diseases, the potential modulation of the selected transmitter.
Program: VEGA
Project leader: Mgr. Lenčešová Ľubomíra PhD.
Duration: 1.1.2013 – 31.12.2015
Univerzitný vedecký park pre biomedicínu Bratislava
Program: Štrukturálne fondy EÚ Výskum a vývoj
Project leader: prof. Ing. Križanová Oľga DrSc.
Duration: 1.3.2013 – 31.12.2015
NanoTechPDT – Využitie biofotonických nanotechnológií k štúdiu mechanizmov bunkovej smrti s cieľom zvýšenia citlivosti detekcie a selektivity liečby nádorov
Towards increased sensitivity of cancer detection and selectivity of cancer treatment: biophotonic nanotechnology applications
Program: APVV
Project leader: RNDr. Bilčík Boris PhD.
Duration: 1.7.2012 – 31.12.2015
Vybudovanie Kompetenčného centra pre výskum a vývoj v oblasti molekulárnej medicíny
Building a Competency Centre for research and development in the field of molecular medicine
Program: Štrukturálne fondy EÚ Výskum a vývoj
Project leader: Ing. Sulová Zdena DrSc.
Duration: 1.10.2011 – 31.10.2015
Bunkové zmeny spojené s nadexpresiou P-glykoproteínu v leukemických bunkách
Overexpression of P-glycoprotein induced cell changes in leukemia cells
Program: VEGA
Project leader: doc. Ing. Breier Albert DrSc.
Duration: 1.1.2012 – 31.12.2014
CEMAN – Centrum excelentnosti na štúdium metabolických aspektov vývoja, diagnostiky a liečby nádorových ochorení
Center of excellence for the treatment of metabolic aspects of development, diagnostics and treatment of cancer diseases
Program: Centrá excelentnosti SAV
Project leader: prof. Ing. Križanová Oľga DrSc.
Duration: 1.7.2011 – 31.12.2014
Glykomika – Centrum excelentnosti pre glykomiku
Center of excellence for glycomics
Program: Štrukturálne fondy EÚ Výskum a vývoj
Project leader: Ing. Sulová Zdena DrSc.
Duration: 1.11.2010 – 31.12.2014
Homeostáza neutrálnych lipidov u kvasiniek: od bunkovej biológie k biotechnológii
Neutral lipid homeostasis in yeast: from cell biology to biotechnology
Program: VEGA
Project leader: RNDr. Hapala Ivan CSc.
Annotation:
Duration: 1.1.2011 – 31.12.2014
Kompetícia medzi Ca2+ a iným katiónom o interakčné miesto lokalizované na luminálnej doméne srdcového ryanodínového receptora a jej vplyv na reguláciu receptora.
Competition between Ca2+ and other cation for luminally located binding site on the cardiac ryanodine receptor and its effect on the receptor regulation.
Program: VEGA
Project leader: Mgr. Gaburjáková Jana PhD.
Annotation: The key determinant of cardiac contractility is Ca2+ released from the sarcoplasmic reticulum (SR) via cardiac ryanodine receptor type 2 (RyR2) that is localized in membrane of the SR. The cytoplasmic domain of the channel has been considered to be the main regulatory region. However, also smaller luminal part contributes to the channel regulation. It has been shown that different divalent cations interact with cytosolic channel activation site (A-site) and compete for binding, thus cytosolic regulation of the channel can be modified. The dominant regulatory ion in the lumen of SR is Ca2+ but Mg2+ is also present. Both ions bind to the luminally located interaction site (L-site) of the RyR2 channel and compete for binding. This could potentially affect the luminal regulation of the RyR2 channel. Our main aim is to perform a comprehensive study of cation competition on luminal face of the RyR2 channel in order to better understand luminal regulation of the RyR2 channel under physiological conditions.
Duration: 1.1.2012 – 31.12.2014
Molekulárna analýza HGD génu a zavedenie in vitro modelu na štúdium potenciálnych terapeutických agensov u pacientov s alkaptonúriou
Molecular analysis of HGD gene and establishment of in vitro model for studying of potential therapeutic agents in pacients with alkaptonuria
Program: VEGA
Project leader: RNDr. Radvánszky Ján PhD.
Annotation: Alkaptonuria (AKU) is an autosomal recessive disease caused by inactivating mutations in the gene for homogentisate-1,2-dioxygenase (HGD), causing an inability to metabolize homogentisic acid (HGA), which is excreted in urine and in the form of ochronotic pigment is deposited in connective tissues, especially in the joints. The disease leads to painful arthritic changes and disability. Worldwide alkaptonuria is a very rare disease. In Slovakia, however, it is up to ten times more common, which provides a prerequisite for successful research. In the present project we plan to carry out molecular biological analyses of the HGD gene in AKU patients from Slovakia and abroad and to establish in vitro model based on the cultivation of chondrocytes of healthy subjects and AKU patients, which will serve for testing potential therapeutic agents.
Duration: 1.1.2012 – 31.12.2014
Nukleo-mitochondriálne interakcie ako hybná sila speciácie
Nucleo-mitochondrial interactions as the driving force for speciation
Program: VEGA
Project leader: RNDr. Hapala Ivan CSc.
Annotation: Yeasts provide a unique opportunity to understand the general principles of evolutionary mechanisms by phylogenomics. However, evolution and the divergence of the species can be studied experimentally through the interspecific hybrids of Saccharomyces cerevisiae with related species via hybrid speciation. The impact of “untuned” nucleo-mitochondrial interactions has been increasingly emphasized in this process, especially if the progeny receives the mitochondrial genome from one species and nuclear genome from another one. The aim of the project is to study the primary sources of interspecific nucleo-mitochondrial (in)compatibility in yeastsrepopulated with the mitochondria from related species and the molecular mechanisms leading to the changes in species-specific gene order in mitochondrial DNA by means of interspecific hybrids.
Duration: 1.1.2012 – 31.12.2014
Plasticita membránových systémov srdcových svalových buniek
Plasticity of the membrane systems of cardiac myocytes
Program: VEGA
Project leader: RNDr. Novotová Marta CSc.
Annotation: In our previous studies, we have shown that cytoarchitecture contributes to intracellular signaling in cardiac myocytes and that cytoarchitectual changes accompany cardiac remodeling. This project aims at characterization of the morphological variability of the sarcolemma and of the sarcoplasmic reticulum with emphasis on the local aspects of excitation-contraction coupling. Changes in the spatial relations of the plasma membrane and of membranes of the sarcoplasmic reticulum will be studied in the mammalian myocardium with the aim to classify and quantify their structural dynamics in the physiologically and pathologically loaded myocardium. Comprehension of the plasticity of the membrane system will be instrumental in understanding of the membrane morphology as the adaptability factor in cardiac myocytes.
Duration: 1.1.2012 – 31.12.2014
Štúdium redoxnej a radikálovej regulácie mitochondriálnych chloridových kanálov zo srdca potkana v podmienkach oxidačného stresu
Study of redox and radical regulation of mitochondrial chloride channels from rat heart under oxidative stress
Program: VEGA
Project leader: Mgr. Tomášková Zuzana PhD.
Duration: 1.12.2012 – 31.12.2014
H2S-NO – Štúdium spriahnutej sulfido-nitrózo signalizačnej cesty H2S
Study of the coupled sulfide-nitroso signaling pathway of H2S
Program: APVV
Project leader: RNDr. Ondriaš Karol DrSc.
Annotation: Study how H2S interacts with NO, and how produvts of the interaction influence membrane channels
Duration: 1.1.2013 – 31.12.2014
MINAPTA – Mechanizmy interakcie malých molekúl s DNA aptamérmi
The mechanisms of interaction small molecules with DNA aptamers
Program: APVV
Project leader: Ing. Šnejdárková Maja CSc.
Annotation:
Duration: 1.5.2011 – 31.10.2014
MITOCHROM – Molekulárna architektúra, dynamika a evolúcia chromozómov v mitochondriách kvasiniek
Molecular architecture, dynamics and evolution of chromosomes in yeast mitochondria
Program: APVV
Project leader: RNDr. Griač Peter CSc.
Annotation: Mitochondrial DNA (mtDNA) molecules and specific proteins form complexes termed nucleoids. These nucleo-protein structures are considered as cytological units of mitochondrial inheritance. Nucleoid proteins participate in the processes of mtDNA replication, expression and repair as well as segregation of the mitochondrial genome during division of eukaryotic cell. The nucleoids associate with mitochondrial inner membrane and several nucleoid proteins are subunits of mitochondrial enzymatic complexes, which illustrates a tight connection of mitochondrial inheritance with membrane functions and organelle metabolism. To understand the molecular principles controlling mitochondrial genome integrity and segregation it is essential to uncover functions of nucleoid proteins and mechanisms of packaging of individual mtDNA molecules into higher order structures, including their molecular architecture. This project proposal is aimed at investigation of mitochondrial genome dynamics, functions of protein components of mitochondrial nucleoids and the molecular architecture of these structures in yeast species containing topologically different forms of mtDNA molecules.
Duration: 1.5.2011 – 31.10.2014
REMOD – Remodelovanie myokardu – úloha vápnikovej signalizácie
Myocardial remodelling – the role of calcium signalling
Program: APVV
Project leader: Ing. Zahradníková Alexandra DrSc.
Annotation: Heart failure is the result of long-term pathological processes that lead to specific damage accompanied by activation of compensatory mechanisms. A common trait, likely due to convergence of many regulatory mechanisms, is the changed calcium signalling in cardiac myocytes. The subject of the project is the impairment of calcium signalling in early stages of myocardial injury with emphasis on the role of the ryanodine receptor (RYR2), a protein central for calcium signalling. The methodology is based on comparing the properties of calcium signalling and the microarchitecture of myocytes of rat myocardium exposed to stress stimuli. Myocardium adapted to spontaneous physical activity will be used as a model of physiologically remodelled myocardium. Myocardium from animals treated with a single high dose of isoproterenol (similar to infracted myocardium) and with a single high dose of streptozotocin (similar to diabetic myocardium) will be used as models of injured myocardium. The effect of stress stimuli on myocardial remodelling will be verified in each subject. The extent of physiological and pathological variability of calcium signalling parameters will be determined by comparison with myocytes from myocardia adapted to sedentary regime. The project will allow identification of molecular and cellular factors determining the function of RYR2 in remodelled myocardium and to deduce the critical sites of calcium signalling impairment.
Project web page: http://www.confolab.sav.sk/data/APVVRe.htm
Duration: 1.5.2011 – 31.10.2014
NeuroCa – Vápnikové kanály v neuronálnej excitabilite
Calcium channels in neuronal excitability
Program: APVV
Project leader: doc. RNDr. Lacinová Ľubica DrSc.
Annotation: Voltage-gated Ca2+ channels (VGCCs) mediate influx of Ca2+ ion, which controls a number of processes including neuronal development and plasticity. L-type voltage-gated Ca2+ channels represent a well-established therapeutic target. Known L-VGCC isoforms (Cav1.2, Cav1.3 and Cav1.4) possess different biophysical properties, thus differentially affecting the dynamics of Ca2+ influx and electrical excitability. This raises a question, to which extent these isoforms contribute to various cellular functions. We will use two established models of neurogenesis: PC12 cell line and primary culture of hippocampal neurons. To analyze role of specific subtypes of L-VGCC we will use method of gene silencing. First we shall optimize cell transfection by siRNA and analyze alteration of structure and function of cell membrane. To assess contribution of Cav1.2 and/or Cav1.3 channels to cellular excitability we will employ whole cell patch clamp measurements. Activity of L-VGCC is in direct relation with activity of other surface transport proteins like Na-Ca-exchanger or Na-K-ATPaze and with activity of intracellular calcium channels like IP3 receptors. We will analyze possible alterations in their expression by PCR method. Altered ratio of transport proteins may affect cell architecture. We will use electron microscopy to assess changes in cell ultrastructure.
Duration: 1.5.2011 – 31.10.2014
LEUPGLY – Zmeny v metabolizme bunky vyvolané nadexpresiou transportéra liečiv P-glykoproteínu v leukemických bunkách
Alternation in cell metabolism asocciated with drug transporter P-glycoprotein overexpression in leukemia cells
Program: APVV
Project leader: Ing. Sulová Zdena DrSc.
Annotation: Multidrug resistance (MDR) of neoplastic cells represent real obstacle in chemotherapy of cancer. Overexpression of membrane protein described as P-glycoprotein (Pgp) represents most often-observed molecular cause of MDR and take place after influence of cytotoxic agents – Pgp substrates on neoplastic cells. We applied the adaptation on vincristine (VCR) in development of L1210/VCR cell subline that exerts besides MDR phenotype several following alterations in phenotype: changes in spectrum of cell surface saccharides, changes in intracellular calcium homeostasis, changes in intracellulars levels of regulatory proteins like stress kinases or nuclear receptors for retinoids. These changes represents mostly pronounced differences between L1210 and L1210/VCR cells and could be induced by adaptation process not directly connected with Pgp expression. Another possibility is that they are directly linked with expression of Pgp in adapted cells as secondary cellular response. To resolve this question we have to compare cells, in which Pgp overexpression was induced by adaptation on drugs with cells overexpressing Pgp due to application of DNA recombination techniques. Therefore, we prepared L1210/T cell sublines that overexpress Pgp due to stable transfection with gene encoding human Pgp. Comparison of L1210/VCR and L1210/T cells from the points of described phenotype changes represent the aim of annotated project.
Duration: 1.5.2011 – 31.10.2014
EpiNeuWel – Epigenetické, fyziologické a neurobehaviorálne aspekty welfaru hydiny
Epigenetic, physiological and neurobehavioural aspects of poultry welfare
Program: APVV
Project leader: RNDr. Košťál Ľubor CSc.
Annotation:
Duration: 1.5.2011 – 30.4.2014
Fertilita – Vplyv telesnej kondície a niektorých imunologických faktorov (CD molekúl) na fertilizačný proces u hovädzieho dobytka
Effect of body condition and some immunological factors (CD molecules) on fertilization process in cattle
Program: APVV
Project leader: Ing. Simon Michal DrSc.
Annotation: The submitted projekt si based on the previous experiments of the team and follows-up the results of their previous project, which were oriented on the increase of the application of reproduction potential of farm animals using reproductive biotechnologies. The project is adequate to current needs of the practis for which the use of these approaches to reach specific breeding purposes will bring economic benefit. In the submitted proposal the mechanisms responsible for occurence of reproductive disorders in dairy cows with deteriorated body condition will be investigated. The research in frame the first of two stages will by mostly focused on the study of foliculogenesis with emphasis to solving the tasks of the influence of body conditions score on the developmental potential of oocyts, preovulatory folicles with definition the factors determining developmet of preimplantation embryos under in vitro conditions.The study of sudden changes of body condition of dairy cows can help in reveling disorders of morfological-functional characterictics, developmental competence and capacity of oocytes following fertilization, what finally might have essential influence on ovarian functions and fertility of mamals.
Duration: 1.5.2011 – 30.4.2014
Dynamika sarkolemy a membránovej iónovej vodivosti srdcových svalových buniek
Sarcolemmal and membrane conductance dynamics in cardiac myocytes
Program: VEGA
Project leader: RNDr. Zahradník Ivan CSc.
Annotation: The sarcolemma of cardiomyocytes represents a complex system, composed of lipids, proteins and membrane cytoskeleton, which forms functional clusters, caveolae, t-tubules and intercellular contacts. In contrast to nerve and secretory cells, the understanding of membrane dynamics of cardiomyocytes is missing, despite its importance in regulation of their physiological functions. Previously, we have developed an exact method for measuring electrical parameters of cardiomyocytes. Here, we utilize the Q-method to portrait the sarcolemmal dynamics in cardiomyocytes by measuring fluctuations of capacitance and conductance, and by analysis of their temporal, correlational, frequency and fractal representations. The data will be interpreted by mathematical modeling. New knowledge on sarcolemmal dynamics of cardiac myocyte will complement the existing picture of cell membrane dynamics and form the basis for studies related to the variability of excitability and contractility and to pathology of heart rhythm.
Duration: 1.1.2011 – 31.12.2013
Energetická výmena a cytoarchitektúra srdcových svalových buniek. Úloha mitochondriálneho proteínu OPA1
Energetic cross-talks and cytoarchitecture of cardiac myocytes. Role of the mitochondrial protein OPA1.
Program: APVV
Project leader: RNDr. Novotová Marta CSc.
Annotation: The objective of this collaboration is to understand the importance of the cytoarchitecture for energetic exchanges and for contractile efficiency. This project is aimed at correlating, during postnatal development in mice, the organization of cell architecture (quantified by electron microscopy) and functioning of energy cross-talks between organelles (measurement of calcium fluxes and contractility). This is a basic science study to explore relationships between cytoarchitecture, energy fluxes and contractility.A second part of the project will get further insight into the mitochondrial network organization in the adult cardiac cell and to investigate how and when its defects precipitate cardiomyocyte failure. Because mitochondrial dynamic is involved in mitochondrial biogenesis, apoptotic cell death, and mitochondrial function and autophagy, we hypothesize that the organization of the mitochondrial network participates in the high efficiency and integrity of mammalian adult cardiomyocyte and that its disruption precipitates energetic inefficiency and cardiac failure.
Duration: 1.1.2012 – 31.12.2013
Faktory determinujúce spriahnuté vrátkovanie ryanodínových receptorov v srdci
Determinants of coupled gating among cardiac ryanodine receptors
Program: VEGA
Project leader: Mgr. Gaburjáková Marta PhD.
Annotation: In the heart, the contraction occurs in response to a small influx of Ca2+ into the myocyte that causes the opening of ryanodine receptors (RyR) and the release of a much larger amount of Ca2+ from the intracellular stores. This process displays an intrinsic positive feedback of released Ca2+ on further release; therefore, a termination mechanism must exist to ensure rhythmic cardiac activity. Coupled gating of RyR channels, one candidate for a shutting mechanism, is manifested by synchronic operation of several RyR channels. The simultaneous closure of all RyR channels in a release unit would break the positive feedback loop and terminate the Ca2+ release. The objective of our work is to identify determinants of coupled gating phenomenon in order to understand the mechanism of inter-channel communication. We will employ the method of ion channel reconstitution into planar lipid membrane that provides detail information about the channel function by recording the current running via the channel pore.
Duration: 1.1.2011 – 31.12.2013
Mechanizmy komunikácie medzi iónovými kanálmi diády kardiomyocytu
Mechanisms of communication among ion channels of cardiomyocyte dyad
Program: VEGA
Project leader: RNDr. Pavelková Jana CSc.
Annotation: Robustness of excitation-contraction coupling in cardiomyocytes is locally ensured by the presence of a large number of DHPR and RyR channels in the dyad. Significant redundancy of the system allows, if necessary, to recruit more channels and thus continuously respond to the increased contractions. This project aims to study the mechanism of interaction between DHPR and RyR channels, mediated by calcium ions, in the cardiomyocytes in situ. We will use a combination of two modern experimental techniques. Voltage clamp method allows us to track response of DHPR channels to voltage stimulus and measure the calcium current value that is a stimulus activating the RyR channels. The method of confocal microscopy enables us to trace the local release of calcium via RyR channels and thereby directly measure their activity in situ. This project will help us understand better the mechanisms regulating communication between the DHPR and RyR channels, and allow us to study the changes of these mechanisms occurring in cardiomyopathies.
Duration: 1.1.2011 – 31.12.2013
Modulácia a funkcia inozitol 1,4,5-trisfosfátových receptorov (IP3R) v neuronálnych štruktúrach pri poškodení centrálneho nervového systému (CNS)
Modulation and function of inositol-1,4,5-trisphosphate receptors (IP3Rs) in neuronal structures of central nervous system (CNS) in normal and pathological conditions.
Program: VEGA
Project leader: Mgr. Pavlovičová Michaela PhD.
Annotation: Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular calcium transporters that modulate calcium level in the cell in physiological processes as well as in response to pathological stimuli. In proposed project we want to elucidate functional and regulation involvement of individual IP3Rs into process of degeneration and regeneration of neurons in CNS lesion. We will effort to define the role of IP3R-mediated calcium signaling in „inability“of injured neuron to continue its neurite outgrowth and regeneration in such pathological conditions. In pathological states of CNS fibrotic scar is created and together with cumulated growth inhibitors prevents further outgrowth and reparation of neuron. On in vitro model of CNS lesion, after stimulation and inhibition of neurite outgrowth, we want to define changes of gene expression of individual IP3Rs (mRNA, protein) in neurons as well as changes in IP3-induced calcium release related to such injury.
Duration: 1.1.2011 – 31.12.2013
Prirodzený systém odmeňovania v mozgu, jeho dopamínergické mechanizmy a welfare hydiny
Natural brain reward system, its dopaminergic mechanisms and poultry welfare
Program: VEGA
Project leader: RNDr. Košťál Ľubor CSc.
Annotation: Animal welfare science solves recently not only the practical problems of the animal „quality of life“, but it also brings new theories. Mechanisms behind several of these concepts have the same denominator – natural brain reward system and mesolimbic dopaminergic system as a part of it. These concepts are for example a concept of welfare based on reward evaluating mechanisms in the brain, using anticipatory behaviour as an indicator for the state of reward systems (SPRUIJT et al., 2001), a concept of affective state induced cognitive bias (HARDING et al., 2004), or a concept of cognitive enrichment (MANTEUFFEL et al., 2009). All these concepts are based on mammalian models and avian or poultry data related to these concepts are scarce. The aim of the project is to contribute to the development of the welfare concepts based on natural brain reward system and to the understanding of their dopaminergic mechanisms in poultry.
Duration: 1.1.2011 – 31.12.2013
VK11 – Štúdium kanálových vlastností
Study of channel properties of novel crown ethers containing polymers in lipid membranes
Program: APVV
Project leader: RNDr. Ondriaš Karol DrSc.
Duration: 1.1.2012 – 31.12.2013
Transport a turnover lipidov: príspevok k poznaniu mechanizmov rezistencie kvasiniek na antifungálne látky a stres
Lipid transport and turnover: contribution to the understanding of yeast resistance to antifungals and stress
Program: VEGA
Project leader: RNDr. Griač Peter CSc.
Annotation:
Duration: 1.1.2010 – 31.12.2013
DNA-DG – Diagnostika spoločensky závažných ochorení na Slovensku, založená na moderných biotechnológiách
Diagnostics of socially important disorders in Slovakia, based on modern biotechnologies
Program: Štrukturálne fondy EÚ Výskum a vývoj
Project leader: prof. RNDr. Kádaši Ľudevít DrSc.
Annotation:
Duration: 1.11.2010 – 31.10.2013
YEASTLIPID – Homeostáza mitochondriálnych lipidov: kvasinka Saccharomyces cerevisiae ako modelový organizmus
Mitochondrial lipid homeostasis: the yeast Saccharomyces cerevisiae as a model organism
Program: APVV
Project leader: RNDr. Griač Peter CSc.
Annotation: Major goal is to study mechanisms regulating optimal membrane lipid composition of eukaryotic cells. Project is focused on the elucidation of the regulatory role of degradation processes in the cardiolipin biosynthetic pathway. Specific items: 1. study of PG degradation, 2. determination of intracellular localization of Pgc1p, 3. study of the physiological role of Pgc1p degradation pathway, 4. possibilities to functionally replace PG for CL, 5. structure-function studies of Pgc1p.
Duration: 1.9.2009 – 30.9.2013
Komplexná mutačná analýza génu zodpovedného za neurofibromatózu typ I
Mutation scanning of the gene responsible for neurofibromatosis type 1
Program: VEGA
Project leader: prof. RNDr. Kádaši Ľudevít DrSc.
Annotation: Neurofibromatosis type 1 (NF1, 1:3500), belongs to the most frequent hereditary diseases frequently leading into a life threatening malignant complications. There is long time need for diagnostics of NF1 in Slovakia. In our project we plan to introduce molecular diagnostic of this disease based on the analysis of complete coding region of NF1 mRNA. After introducing this diagnostics we will screen RNA samples of the available patients (also retrospectively). Suggested screening protocol enables 95% mutation detection rate [1]. In this package we will also investigate collected tumours, first of all imunohistochemically, as well as for the presence of „second-hit“mutation. In order to do this we will also introduce the selective cultivation of the Schwann cells from tumours. Complex mutation analysis of the responsible gene, that has not been routinely available in Slovakia yet, is inevitable for an elaboration of accurate and early diagnosis of NF1 as well as for following genotype-phenotype correlations.
Duration: 1.1.2010 – 31.12.2012
Mechanizmus regulácie jednotlivých typov IP3 receptorov a ich funkcia
Program: VEGA
Project leader: prof. Ing. Križanová Oľga DrSc.
Duration: 1.1.2010 – 31.12.2012
Mechanizmy regulácie diastolickej aktivity ryanodínového receptora
Mechanisms of regulation of the diastolic activity of the ryanodine receptor
Program: VEGA
Project leader: Ing. Zahradníková Alexandra DrSc.
Annotation: Defects of myocardial diastolic function that occur in failing heart or due to mutations in the calcium release channel RyR may result in reduced calcium contents of the intracellular stores. At the same time they may, however, induce spontaneous calcium release during the diastole. Spontaneous calcium release may generate action potentials by activating the Na/Ca exchange. Diastolic regulation of calcium store contents by RyRs can be observed as “calcium sparks” by means of confocal microscopy. Regulation of RyR activity at low levels of cytoplasmic Ca2+ is not clearly understood yet. In this project we propose to study modulation of RyR activity by natural regulators such as ATP, Mg2+ and luminal calcium at the level of single RyR channels and at the level of isolated cardiac myocytes. The results of the project will enable deeper understanding of control mechanisms governing RyR activity during the diastole and identification of their malfunction in cardiac diseases.
Project web page: http://www.confolab.sav.sk/data/VEGAAZ.htm
Duration: 1.1.2010 – 31.12.2012
Modulácia mitochondriálnych kanálov zo srdca potkana sírovodíkom
Modulation of rat heart mitochondrial channels by hydrogen sulfide
Program: VEGA
Project leader: RNDr. Ondriaš Karol DrSc.
Annotation: Recently, it is found that endogenously produced gas transmitter, hydrogen sulfide (H2S), regulates manyphysiological and pathological processes, for example, neuromodulation, proliferation of cells, apoptosis, heartregulation, cardioprotection, ischemia-reperfusion, hypertension, muscle relaxation, inflammation, erection andatherosclerosis. Mechanisms and involvement of mitochondria in these processes are mostly unknown. Toexplain the numerous biological effects of H2S and involvement of mitochondria in these processes, we plan tostudy influence of H2S and mixture of H2S-nitric oxide (NO) on mitochondrial channels. Isolated membranes fromrat heart mitochondria will be incorporated into bilayer lipid membrane (BLM), and effects of H2S and H2S-NO onelectrical properties of single potassium, calcium and promiscuous channels will be studied. An understanding ofthe influence of H2S and H2S-NO on these channels can potentially contribute to treat the negative phenomenain organisms, mention above.
Duration: 1.1.2010 – 31.12.2012
Regulácia vrátkovania T-typu vápnikového kanála
Regulation of the gating of the T-type calcium channel
Program: VEGA
Project leader: doc. RNDr. Lacinová Ľubica DrSc.
Annotation: Enhanced activity of low-voltage-activated (LVA) calcium channels is involved in pathology of severalneurological diseases including childhood absence epilepsy. These channels are distinguished fromhigh-voltage-activated calcium channels by low activation threshold, fast kinetics of activation and inactivationand slow deactivation. We will concentrate on identification of structural determinants of specific gating propertiesof the CaV3.1 channel, representative of LVA channels. For this aim we will construct series of channel mutantstargeting putative interaction site between the channel voltage sensor and the channel conductive pore. Further,we will analyse role of regions in which single nucleotide polymorphism for childhood absence epilepsy werereported. Based on our results functional model of the CaV3.1 channel gating will be developed.
Duration: 1.1.2010 – 31.12.2012
Štúdium vzťahu Na+/Ca2+ výmenníka a ostatných transportných systémov pre vápnik
Program: VEGA
Project leader: RNDr. Hudecová Soňa CSc.
Duration: 1.1.2010 – 31.12.2012
Úloha dopamínergického systému v neurogenéze a regenerácii mozgu vtákov
The role of dopaminergic system in neurogenesis and brain regeneration in birds
Program: VEGA
Project leader: Mgr. Niederová Ľubica PhD.
Annotation: Neurogenesis, the rise of new neurons, does not occur only in the embryonal and early postembryonal stages but it was shown and proven also the brain of adults. Since then it is in the center of attention of many studies because it gives a potential for brain regeneration after various types of damage, including neurodegenerative diseases. Our aim is to study the function of dopaminergic system in the processes of neurogenesis and brain regeneration in songbirds. Neurogenesis in songbirds in comparison with mammals is more intense and the new born neurons are incorporated into the whole telencephalon. We will focus in this project on the study of striatal regeneration. Striatum is a part of basal ganglia and it has functions in motor control as well as in learning. Results of our studies can help to understand regeneration and recovery mechanisms of damaged striatum.
Duration: 1.1.2010 – 31.12.2012
Vplyv nadexpresie P-glykoproteínu a navodenia viacliekovej rezistencie na niektoré aspekty metabolizmu
Effect of overexpression of P-glycoprotein and development of multidrug resistance on some aspects of metabolism
Program: VEGA
Project leader: Ing. Sulová Zdena DrSc.
Annotation: Expression of P-glycoprotein (P-gp) confers multidrug resistance of neoplastic cells. P-gp represents transport ATPase of plasma membrane that secures elimination of substances from intracellular space. Several studies documented that overexpression of P-gp in cells is associated with the changes in cell morphology, in composition of cell surface saccharides that induced alteration in binding of lectins on cell surface. We have described the overexpression of P-gp is associated with changes in expression of several endoplasmic reticulum proteins involved in calcium homeostasis. This was accompanied with increased sensitivity of cells to elevation in extracellular calcium concentration and depression of cell sensitivity to thapsigargin (inhibitor of endoplasmic reticulum calcium pump). The current project will be focused on the study of phenomena that are associated with P-gp overexpression in leukemia cells using biochemical methods combined with cytochemical methods using electron and confocal microscopy
Duration: 1.1.2010 – 31.12.2012
MoMRyR – Mechanizmy zlyhania funkcie ryanodínového receptora
Mechanisms of ryanodine receptor dysregulation
Program: APVV
Project leader: Ing. Zahradníková Alexandra DrSc.
Annotation: Contraction of cardiac muscle is evoked by calcium release from intracellular stores into the cytoplasm. In a healthy cardiac myocyte, massive calcium release occurs only during the systole in response to processes that follow membrane depolarization. Due to increased calcium release during the diastole that occurs in many cardiac diseases, calcium contents of the stores and systolic contraction are decreased, while the propensity to massive spontaneous calcium release, delayed afterdepolarizations and arrhythmias is increased. The scientific objective of this project is to elucidate the regulation mechanisms of diastolic calcium release via the calcium release channel (RyR), and to define the effects of changes in RyR gating on calcium handling and calcium signaling in the cardiac myocyte. These studies will enable to identify defects of calcium handling in cardiac disease.
Project web page: http://www.confolab.sav.sk/data/APVVLPP.htm
Duration: 1.9.2009 – 31.8.2012
TRANSMED 2 – Centrum excelentnosti pre translačný výskum v molekulárnej medicíne (TRANSMED 2)
Center of excellence for the translational research in molecular medicine
Program: Štrukturálne fondy EÚ Výskum a vývoj
Project leader: prof. Ing. Križanová Oľga DrSc.
Duration: 1.6.2010 – 31.5.2012
TRANSMED 2 – Centrum excelentnosti pre translačný výskum v molekulárnej medicíne 2 (TRANSMED 2)
Centre of Excellence for translational research in molecular medicine (TRANSMED 2)
Program: Štrukturálne fondy EÚ Výskum a vývoj
Project leader: RNDr. Hapala Ivan CSc.
Annotation:
Duration: 1.6.2010 – 31.5.2012
Biofyzikálne princípy regulácie napäťovo závislých iónových kanálov v zdraví a chorobe
Biophysical principles of voltage dependent ion channels regulation in health and disease
Program: Iné projekty
Project leader: doc. RNDr. Lacinová Ľubica DrSc.
Annotation: Aim of the project is to develop curicullum for new course for pharmacology students in 7th semester. In addition to lectures and seminars textbook in slovak and english language will be published and presentations for e-learning will be prepared.
Duration: 1.1.2009 – 31.12.2011
MYOPHYS – Bunková a molekulárna fyziológia kardiomyocytov
Cell and molecular physiology of cardiomyocytes
Program: APVV
Project leader: Ing. Zahradníková Alexandra DrSc.
Annotation: Understanding the mechanisms of function of cardiac myocytes and of their dysfunction in cardiovascular diseases is the basic prerequisite for targeted therapy. The aim of this project is to find the relationships between signalling and energetic functions of cardiac myocytes that are mediated by the interaction between membrane potential, cellular redox state, and diastolic calcium release, using the methods of electrophysiology, biochemistry and molecular biology. The complementary know-how of the partner institutions will bring methodological enrichment and will enable a higher level of understanding of the studied mechanisms.
Duration: 1.1.2010 – 31.12.2011
Dlhodobý pobyt prepelice japonskej v simulovanej mikrogravitácii
Long-term stay of Japanese quail in simulated microgravity
Program: VEGA
Project leader: Ing. Škrobánek Peter CSc.
Annotation: The project represents a continuation of our previous research of the development of Japanese quail reproductive ability in simulated microgravity to 63 days of age. It studies the effects of chronic hypodynamia on the adaptability, reproductive capacity and performance properties of male and female Japanese quail to 180 days of age. The differences in the selected organ and tissue features of quail exposed to hypodynamia will be studied by morphological, physiological and biochemical methods. The data obtained from study will be utilized in future experiments concerning quail ontogeny in the real weightless environment – microgravity.
Duration: 1.1.2009 – 31.12.2011
Efekt fyziologickej koncentrácie luminálneho Ca2+ na funkčné vlastnosti ryanodínového receptora zo srdca potkana
Regulation of cardiac ryanodine receptor by physiological concentration of luminal Ca2+
Program: VEGA
Project leader: Mgr. Gaburjáková Jana PhD.
Annotation: In cardiac muscle, the Ca2+ required for contraction is rapidly released from the sarcoplasmic reticulum (SR) via ryanodine receptor/Ca2+ channel type 2 (RYR2). The big cytoplasmic part of RYR2 was considered as a main regulatory domain, where the binding sites for various ligands are localized. However, there is growing evidence that Ca2+ in the lumen of the SR can also be effectively involved in the regulation of channel function. On the single channel level, it has been shown that luminal Ca2+ potentiates sensitivity of the RYR2 channel to the cytoplasmic ligands as well as slows down the gating kinetics. Up to date, effect of luminal Ca2+ was described only for high non-physiological concentrations, while estimated concentration of Ca2+ in the SR lumen is 1mM. So, we need to answer the question how luminal Ca2+ regulates the RYR2 channel function at physiological concentration. Therefore, our aim is to systematically examine effect of 1mM luminal Ca2+ on the functional properties of the RYR2 channel.
Duration: 1.1.2009 – 31.12.2011
Evolučné paradoxy mitochondrií a ich genómov (petitnosť a architektúra)
Evolutionary paradoxes of mitochondria and their genomes (petiteness and architecture)
Program: VEGA
Project leader: RNDr. Hapala Ivan CSc.
Annotation:
Duration: 1.1.2009 – 31.12.2011
BOVCD – Identifikácia a funkčná analýza CD molekúl (antigénov) na somatických a pohlavných bunkách hovädzieho dobytka
Identification and functional analysis of the CD molecules on the somatic and gametic cells of cattle
Program: VEGA
Project leader: Ing. Simon Michal DrSc.
Annotation: CD antigens are characteristic molecules of the cell membranes. These molecules have important role in different immune processes. They mediate some interactions between immunocompetent cells and communication of these cells with the components of cell matrix. The project is focused on the identification of the CD molecules of the somatic and the gamete cells of cattle using monoclonal antibodies with defined specificities. The production of new monoclonal antibodies against bovine cells will be included in the project and the analysis of cross-reactivity of the produced antibodies with pig and rabbit cells will be also studied. In the proposed project we should concentrate to the function of four molecules (CD46, CD52, CD9 and CD11/18) in the reproduction process.
Project web page: http://www.ubgz.sav.sk
Duration: 1.1.2009 – 31.12.2011
Mutačná analýza génu LRRK2 a iných vybraných génov asociovaných so vznikom Parkinsonovej choroby
Mutation analysis of LRRK2 gene and other slected genes associated with Parkinson disease development
Program: VEGA
Project leader: Mgr. Zaťková Andrea PhD.
Annotation: Proposed project maps the variability of LRRK2 gene, mutations of which are the most common amongparkinsonic patients and other genes associated with Parkinson disease (PD) on the DNA level. Accomplishmentof the project should contribute to understanding genotype-clinical phenotype relation, provides precondition forDNA diagnostics methods and prognosis estimation, and represents the first step towards effective causativetherapy. Completing the project includes creating reference DNA bank of patients with sporadic and familiar formof PD, mutation screening based on DHPLC, HRM and DNA sequencing methods, optimization of PCRconditions for amplicons covering coding regions of LRRK2 gene and other genes, development and applicationof an effective system of mutation analysis, elaboration of PCR based detection methods for DNA diagnostics ofidentified causative mutations, and linkage analysis within families with multiple occurrences of PD for newdisease genes identification purpose in Slovak population.
Duration: 1.1.2009 – 31.12.2011
Remodelácia cytoarchitektúry kardiomyocytov vo funkčne modifikovanom myokarde.
Remodeling of cytoarchitecture of cardiomyocytes in functionally modified myocardium
Program: VEGA
Project leader: RNDr. Novotová Marta CSc.
Annotation: Changes in the internal organization of cardiac myocytes may play a critical role in failing myocardium. We have shown previously that cytoarchitecture determines functional as well as energetic interactions in muscle cells and characterizes cell remodeling. The project focuses on stereologic analysis of spatial relations among organelles in cardiac myocytes of healthy mice, of mice with blocked expression of desmine (related to dilated cardiomyopathy), and of mice expressing mutated RyR2 (calcium release channel related CPVT arrhythmia in humans). The aim of the project is to understand the role of cytoarchitecture of cardiac muscle cells in excitation-contraction coupling. Stereologic analysis of changes in amount and distribution of cell organelles will provide a new insight on adaptability of microdomains to changes in calcium signaling. This study will help to estimate consequences of changed cell architecture on function of myocardium in pathological states.
Duration: 1.1.2009 – 31.12.2011
Vplyv beta-blokátorov na elektrickú aktivitu a ultraštruktúru myokardu po remodelácii navodenej izoprenalínom
Program: VEGA
Project leader: RNDr. Novotová Marta CSc.
Duration: 1.1.2010 – 31.12.2011
Vzťah iónovej homeostázy a dynamiky organel eukaryotickej bunky
Relationships between ion homeostasis and organelle dynamics in eukaryotic cells
Program: VEGA
Project leader: RNDr. Griač Peter CSc.
Annotation: Membrane compartments of the eukaryotic cell must be able of flexible adjustments to the changes in extra- andintracellular environment. The adjustments are in part manifested by changes in the organelle morphology andthe corresponding organellar physiological activities. Our proposal is based on our results of analysis of yeastmutants resistant to mitochondrial ionophores valinomycin and nigericin indicating a close relationship betweenregulation of ion homeostasis and dynamics of yeast mitochondria and vacuoles. We plan to study the cellularroles of proteins identified in our laboratories as key players in mediating the effect(s) of ionophores and tounderstand the molecular principles of regulation of mitochondrial ion homeostasis and its relationships tomitochondrial and vacuolar dynamics. The ultimate goal of the project is to employ our data for modeling anetwork of cellular components involved in coordinated response of a eukaryotic cell to the changes in theintracellular distribution of ions.
Duration: 1.1.2009 – 31.12.2011
Zmeny leukemických buniek pozorované pri rozvoji viacliekovej rezistencie spojenej s nadexpresiou P-glykoproteínu
Changes of leukemia cells associated with P-glycoprotein mediated multidrug resistance development
Program: VEGA
Project leader: doc. Ing. Breier Albert DrSc.
Annotation: We plan to find processes associated with P-glycoprotein (Pgp) mediated multidrug resistance (MDR)development in neoplastic cells. Overexpression of Pgp in neoplastic cells is often induced by adaptation of cellsto cytotoxic effects of several substances in their sublethal concentrations. Several changes of cell regulationand metabolic pathways are involved in the development of this type of MDR together with massiveoverexpression of Pgp and these changes are responsible for alteration in several cell processes like energyproduction, protein phosphorylation or entering to apoptosis etc. These alterations may be induced directly byoverexpression of Pgp or by chemical stress during cell adaptation. The aim of this project is to recognize whichone from the latter two possibilities is valid in the respective changes associated with this type of MDR. We willuse mice leukemia L1210 cells that overexpress Pgp due to adaptation to vincristine or due to stable transfectionwith human mdr1 gene encoding Pgp.
Duration: 1.1.2009 – 31.12.2011
Zmeny v ATP syntetizujúcom systéme mutantov methanoarchaea M.thermautotrophicus rezistentných k N,N-dicyclohexylkarbodiimidu, tributylcínu a diethylstilbesterolu
Alterations of the ATP synthesizing systems in N,N´-Dicyclohexylcarbodiimide, tributyltin and diethylstilbesterol resistant mutants of methanoarchaeon Methanothermobacter thermautotrophicus
Program: VEGA
Project leader: Doc. RNDr. Šmigáň Peter DrSc.
Annotation: Methanoarchaea are stictly anaerobic microorganisms producing methane . Methanogenesis drives the formation of primary electrochemical gradients of H+ and Na+ across a membrane. These gradients are coupled with ATP synthesis via ATPsynthase(s). We have suggested on the basis of inhibitory experiments the existence of two ATPases in cells of M. thermoautotrophicus . In an attempt to explain the participation of these ATPases in ATP synthesis we isolated and characterized a mutant resistant to DCCD –dicyclohexylcarbodiimide. This mutant has a lesion in ATPsynthetising machinery. The main goal of this project will be a detailed biochemical and molecular analysis of ATPases sytems of this mutant and isolation and characterization of mutants resistant to tributyltin and DES(diethylstilbesterol) –inhibitors of A1A0 ATP synthase. We will contribute to the explanation of molecular mechanisms of ATP synthesis in methanoarchaea
Duration: 1.1.2009 – 31.12.2011
Biomembrány – Biomembrány: štruktúra a dynamika membrán vo vzťahu k bunkovým štruktúram
Biomembranes: Membrane structure and dynamics in relation to cell functions
Program: APVV
Project leader: RNDr. Hapala Ivan CSc.
Annotation: Centre of excellence (CE) Biomembranes is aimed at establishing a functional network of research laboratories showing excellence in specific areas of membrane research. The study of biomembranes s a dynamic system and of membrane functions essential for the existence of cells and organisms will be the integrative aspect in the activities of CE. The activities of CE will be focused on the support of cooperation between member laboratosies in the study of membrane involvement in the etiology of cardiovascular and transmissive diseases, neurological disorders and diabetes, as well as in some biotechnologies, such as production of transgenic animals, production of biofuels, or designing of biosensors. Sharing advanced methods and equipment available in individual laboratories will represent a significant integrative aspect of CE. Center will provide a platform for joint project applications and for the integration of Slovak laboratories in international projects. An important aim of the project will be improvement of the training of PhD students and postdocs for the professional career in membrane research. To increase the attractiveness of mebrane research for young scientists, CE will provide improved social and professional conditions for this target group. Considering the important role of membranes in biomedicine and several biotechnological processes, CE will serve as an informational and methodological center open for all institutions involved in biomedical and biotechnological research.
Duration: 1.7.2008 – 31.10.2011
Biomembrány – Biomembrány: štruktúra a dynamika biologických membrán vo vzťahu k bunkovým funkciám
Biomembranes: structure and dynamics of biological membranes related to cell functions
Program: APVV
Project leader: doc. RNDr. Lacinová Ľubica DrSc.
Annotation:
Duration: 1.7.2008 – 30.6.2011
TRANSMED 1 – Centrum excelentnosti pre translačný výskum v molekulárnej medicíne (TRANSMED1)
Centre of Excellence for translational research in molecular medicine (TRANSMED1)
Program: Štrukturálne fondy EÚ Výskum a vývoj
Project leader: RNDr. Hapala Ivan CSc.
Duration: 21.5.2009 – 20.5.2011
TRANSMED – Centrum excelentnosti pre translačný výskum v molekulárnej medicíne (TRANSMED)
Center of excellence for the translational research in molecular medicine
Program: Štrukturálne fondy EÚ Výskum a vývoj
Project leader: prof. Ing. Križanová Oľga DrSc.
Duration: 19.5.2009 – 30.4.2011
CEKVY – Centrum excelentnosti pre kardiovaskulárny výskum
Center of excellence for cardiovascullar research
Program: Centrá excelentnosti SAV
Project leader: prof. Ing. Križanová Oľga DrSc.
Duration: 1.1.2007 – 31.12.2010
IP3 receptory, ich modulácia a funkcia za normálnych a patologických podmienok
Program: APVV
Project leader: prof. Ing. Križanová Oľga DrSc.
Duration: 1.6.2008 – 31.12.2010
Kvasinky ako nástroj pre produkciu biotechnologicky hodnotných steroidov: biochemický a genetický prístup
Yeast as a tool for producing biotechnologically valuable sterols: the biochemical and genetic approach
Program: APVV
Project leader: RNDr. Hapala Ivan CSc.
Annotation: Squalene and steryl glycosides are intermediates of sterol metabolism that find a broad application in food indistry, pharmacology and other biotechnologies. Considering limited natural resources of these metabolites, yeast represent an interesting alternative for their production for commercial use. The project is aimed at extending the basic knowledge about the mechanisms controlling metabolism and intracellular distribution of squalene and steryl glycosides in yeast Saccharomyces cerevisiae and Pichia pastoris. Factors enabling to increase their production in zyeast cells will be studied by microbiological, biochemical and genetic methods. Knowledge obtained in these experiments will be used for engineering of producer strains that could find application in food industry and other branches of biotechnology.
Duration: 1.6.2008 – 31.12.2010
Modulácia vápnikovej signalizácie v sarkoplazmatickom retikule pri zlyhaní srdca
Modulation of calcium signaling in the sarcoplasmic reticulum in heart failure.
Program: VEGA
Project leader: RNDr. Zahradník Ivan CSc.
Annotation: The inotropic properties of the heart cell are determined by the efficiency of excitation – contraction coupling. When this efficiency is lost, contractile dysfunction and heart failure develop – the main causes of death in the Western world. The cellular and molecular defects that cause depressed contractility of failing myocytes are not well understood but seem to culminate in abnormal uptake, storage and release of calcium by the main calcium storage organelle of the cell – sarcoplasmic reticulum. The overall goal of this project is to study changes in calcium signaling inside this delicate intracellular structure and address their importance for the defect cellular Ca handling in HF. We will use confocal microscopy, a novel advanced experimental technique for registration ofcalcium signals, together with mathematical modeling. The outcomes of our project will contribute to better understanding of aetiology of heart failure and to the improvement of prophylactic and therapeutic precedures ofthis disease.
Duration: 1.1.2008 – 31.12.2010
Molekulárna analýza závažných dedičných neuromuskulárnych a neurodegeneratívnych ochorení
Molecular analysis of severe inherited neuromuscular and neurodegenerative diseases
Program: VEGA
Project leader: prof. RNDr. Kádaši Ľudevít DrSc.
Annotation: Neurodegenerative and neuromuscular inherited diseases belong to severe clinical entities that require special management and therapy, which doesn’t have to be successful in all cases. There is no other possibility today to diagnose the preclinical phase of these diseases than by genetic tests. DNA diagnostics enable the identification of “affected” patients in preclinical stage; moreover for example in the case of DM1 it enables identification of asymptomatic carriers and utilization of prenatal diagnosis in at risk families. For the introduction of DNA analysis of DM1, CMT1A and HNPP in clinical practice, establishment of new methodic approaches is essential, but it also requires the detailed knowledge of the mutational status of these genes in the Slovakpopulation, which enables the optimization of the methodic approaches and their utilization in clinical practice.
Duration: 1.1.2008 – 31.12.2010
Molekulárne mechanizmy regenerácie bazálnych ganglií u spevavcov
Molecular Mechanisms of Basal Ganglia Regeneration in Songbirds
Program: Podpora MVTS z prostriedkov SAV
Project leader: Mgr. Niederová Ľubica PhD.
Annotation:
Duration: 1.1.2008 – 31.12.2010
Monitorovanie welfaru hydiny s využitím behaviorálnych a rádiotelemetrických metód
Monitoring of poultry welfare using behavioural and radiotelemetric methods
Program: VEGA
Project leader: RNDr. Bilčík Boris PhD.
Annotation: Intensive breeding technologies together with genetic selecion aimed at maximization of production often contribute to poor welfare of farm animals. Consequence is the occurrence of abnormal behaviours and changes in physiological parameters and health. The study of abnormal behaviours, knowledge of causal factors andpossibilities of prevention are important both for animal production and ethics. Poultry welfare is getting more attention due to EU legislation which bans the use of cages and replaces them with alternative breeding systems. To evaluate welfare objectively it is necessary to measure and analyse behaviour as well as a wide range of physiological functions. Radiotelemetry enables obtaining data in freely moving animals. The aim of this proposal is to develop the application of radiotelemetry for measuring physiological parameters in poultry and together with behavioural methods to characterise the effects of various conditions relevant to the welfare oflaying hens and meat type chickens.
Duration: 1.1.2008 – 31.12.2010
Nadexpresia P-glykoproteínu a s ňou spojené zmeny v spektre a v hladinách bunkových oligo- a polysacharidov
Overexpression of P-glycoprotein and associated changes in spectrum and levels oligo- and polysaccharides
Program: APVV
Project leader: Ing. Sulová Zdena DrSc.
Duration: 1.6.2008 – 31.12.2010
NANOBIOSENS – Nanoštruktúry pre vývoj biosenzorov
Nanostructures for development of biosensors
Program: APVV
Project leader: Ing. Šnejdárková Maja CSc.
Duration: 1.9.2008 – 31.12.2010
Neurobiologické mechanizmy regulácie ozobávania peria u nosníc
Neurobiological control mechanisms of the feather pecking in laying hens
Program: VEGA
Project leader: RNDr. Košťál Ľubor CSc.
Annotation: Feather pecking, pecking directed to and damaging the feathers of other birds, is a behavioural disorder occurring in laying hens and other poultry species and breeds. Feather pecking is both a welfare and economic problem. Council Directive 1999/74/EC of 19 July 1999 laying down minimum standards for the protection of laying hens approved banning of conventional battery cages from 2012 in order to improve their welfare. Thus in the next few years major changes to the housing of laying hens in Europe will occur. An increased risk of feather pecking is a main obstruction to the wide adoption of alternative housing systems, such as free range, aviaries or percheries. The proposed project is focused at the study of neurobiological bases of this abnormal behaviour, especially at the use of immediate early genes expression for the identification of the brain regions underlyingthis behaviour and the role of the dopaminergic system in ithese mechanisms.
Duration: 1.1.2008 – 31.12.2010
cleanergy – Využitie komplexných prírodných organických materiálov (KPOM) na energetické účely s použitím netradičných mikroorganizmov
Exploitations of complex organic materials by means of non-traditional micro-organisms for energetic purposes
Program: APVV
Project leader: Doc. RNDr. Šmigáň Peter DrSc.
Annotation: Microbial degradation of complex materials, including waste products of biotechnology as a potential source of clean energy carriers such as. hydrogen and metán.Microbial degradation of these materials that takes place in nature under uncontrolled conditions, in the laboratory has been studying for decades. The project aims to initiate research on the biological production of hydrogen from complex organic materials and develop new approaches for the biodegradation of these materials using non-traditional anaerobic fungi with the possibility of using hydrogen in methanogenesis and develop more efficient methods for degradation of lignin by filamentous bacteria.
Duration: 1.9.2008 – 31.12.2010
– – Antimykotiká ako nástroj pri štúdiu biogenézy membránových lipidov u kvasiniek
Antimycotics as a tool for the study of membrane lipid biogenesis in yeast
Program: VEGA
Project leader: RNDr. Hapala Ivan CSc.
Annotation: Project is aimed at the the analysis of the antimycotic substances that affect various processes linked to functions and biogenesis of membrane lipids in the yeast Saccharomyces cerevisiae: terbinafine (inhibitor of ergosterol synthesis on the level of squalene epoxidation), amphotericin B (memrane active substance forming complexes with ergosterol) and cerulenin (inhibitor of fatty acid synthesis). The general emphasis is given to the effects of specific processes influenced by the antimycotics on general lipid homeostasis in yeast cell and on functions of cell membranes. Particular problems studied in the project are the biogenesis of lipid particles (e.g. squalene accumulation after terbinafine treatment, regulation of triglyceride synthesis in cerulenin-treated cells) and the dynamics of membrane domains (rafts) in cells treated with amphotericin B. The specific effects of terbinafine, amphotericin B and cerulenin on membrane biogenesis are studied with the focus on the antimycotic effect of these substances.
Duration: 1.1.2007 – 31.12.2009
Bunkový objem a sekrécia inzulínu
Cell volume and insulin secretion
Program: APVV
Project leader: RNDr. Hapala Ivan CSc.
Annotation: Cell volume regulation is considered to be integrated into a signal transduction network regulating cell fuction. Cell swelling evokes endocytosis of proteins and peptides stored in secretory vesicles from various cell types. Dynamics of this type of hormone secretion is indistinguishable from that induced by natural secretagogue. Hyposmotic stimulation of insulin secretion is independent from the extra- and intracellular Ca2+, does not involve protein kinase C and other intracellular mediators of glucose stimulation, and could not be inhibited by noradrenaline. These data indicate a novel signalling pathway for stimulation of insulin secretion exploited by cell swelling. Recently we have compared rat pancreatic cell lines and found that while both INS-1 and INS-1E cell lines release insulin in response to glucose, only INS-1 cells release insulin in response to cell swelling. Comparison of gene expression by DNA microarray and properties of plasma membranes could be a key to discovery of the transduction pathway of the swelling-induced exocytosis.
Duration: 1.1.2007 – 31.12.2009
Neurobiológia vokálnej komunikácie u vtákov
Neurobiology of vocal communication in birds
Program: VEGA
Project leader: Mgr. Niederová Ľubica PhD.
Annotation: The aim of this project is to study the function of the vocal basal ganglia loop for the vocal communication in songbirds and parrots. Here we propose to use a unique approach by combining different species selected according to their song variability. The function of the basal ganglia loop was previously studied in zebra finches that learn the song as juveniles but do not change it as adults and are therefore considered ‚close-ended learners‘ with a very stereotyped song. Our preliminary studies suggest that it is critical to study these mechanisms in species that learn or modulate the song as adults. Therefore our study combines three species: the ‚close-ended learner‘ zebra finch with stereotyped song, canary with seasonal changes of song (adding new syllables before and after the breeding season), and budgerigar that maintains the song plasticity and is therefore considered an ‚open-ended‘ learner, similarly as humans. At the end of the experiment we will assess the molecular consequences of the changed motor output. The understanding of behavioral and molecular consequences of basal ganglia damage for the learned vocal communication is potentially valuable for understanding of pathogenesis of the related human diseases and for development of their successful therapies.
Duration: 1.1.2007 – 31.12.2009
Nanobiosens – Štúdium afinitných interakcií na nanoštruktúrnych substrátoch dendriméroch pomocou kremenných mikrováh
Study of the affinity interaction on the nanostructured substrates dendrimers via quarz crystal microbalances
Program: VEGA
Project leader: Ing. Šnejdárková Maja CSc.
Annotation: We focused on the optimalization of the immobilization of monoclonal antibody PRI308(mAb-PRI308)on the gold crystal.The oriented immobilization onto surface of QCM crystal involves thiol, nanostructure dendrimer PAMAM G4, neutravidin and protein-A modified by biotin. The last step of the immobilization process was captured of the mAb-PRI308 in quantities 2 000ng/ml . This step caused the decrease of change frequency about -49 Hz. The interaction between mAb-PRI308 and PrP-pure prion proteins were measured by the quartz crystal microbalance (QCM)as changes of the frequency in the interval 10-5000 ng/ml of PrP-pure prion proteins.
Project web page: UBGZ_SAV
Duration: 1.1.2007 – 31.12.2009
Štúdium interaktívneho miesta P-glykoproteínu s derivátmi pentoxifylínu
Study of the interactive binding site of P-glycoprotein with pentoxifylline derivatives
Program: VEGA
Project leader: Ing. Dočolomanský Peter CSc.
Annotation:
Duration: 1.1.2007 – 31.12.2009
Transgeneračný prenos hormónov a následné adaptácie počas postnatálneho vývinu živočíchov
Transgeneration transfer of hormones and subsequent control mechanisms
Program: VEGA
Project leader: Ing. Výboh Pavel CSc.
Annotation: Project investigates environmental conditions influencing physiological systems via maternal hormones and behaviour of precocial Japanese quail and rats. We focus on transgenerational transfer of steroids (testosterone, corticosterone) and leptin, which can represent a signal mediating information about nutritional conditions of females during egg formation period to embryos. Effects of leptin will be determined on chorioallantoic membrane of developing quail embryos under both in vitro and in vivo conditions. Development of circadian system in chicken during perinatal development will be assessed on the basis of clock gene expression in the master (the pineal gland) and peripheral oscillators. Functional consequences on entire organism will be studied using cardiovascular system activity and changed plasma melatonin concentrations and melatonin receptor activity in peripheral tissues.
Duration: 1.1.2007 – 31.12.2009
Transport a trunover fosfolipidov ako regulačné mechanizmy lipidového zloženia membrán u kvasinky Saccharomyces cerevisae
Transport and turnover of phospholipidis as regulatory mechanism of membrane lipid composition in yeast Saccharomyces cerevisae
Program: VEGA
Project leader: RNDr. Griač Peter CSc.
Annotation: The proposed project is oriented toward the elucidation of mechanisms how a model unicellular eukaryotic microorganism, yeast Saccharomyces cerevisie, maintains optimal lipid composition of its membranes. It is focused on two aspects of membrane lipid homeostasis: turnover of phospholipids and their intracellular transport. The specific goals of the project are to understand the role of phosphatidylinositol transfer proteins (PITP) in metabolism of phospholipids and the study of degradation processes in the biosynthetic pathway leading to the formation of the major mitochondrial anionic phospholipid, cardiolipin. The major yeast PITP, Sec14p, has an important role in regulation of the intracellular transport and together with other PITPs of this microorganism regulates the optimal lipid membrane composition. Understanding the molecular mechanisms how Sec14p fulfills its role at the interface of lipid metabolism with the membrane trafficking could contribute to the understanding of neurodegenerative and metabolic malfunctions associated with defects in PITP functions in mammals. Similarly, knowledge of the mechanisms how eukaryotic cells regulate their anionic phospholipids metabolism could help in understanding the role of phosphatidylglycerol and cardiolipin in cellular physiology.
Duration: 1.1.2007 – 31.12.2009
Zmeny v metabolizme neoplastických buniek sprevádzajúce navodenie „multidrug“ rezistencie sprostredkovanej P-glykoproteínom postupnou adaptáciou senzitívnych buniek na cytostatiká
Changes of neoplastic cell metabolism associated with development of p-glycoprotein mediated miltidrug resistance induced by adaptation of sensitive cells to drugs
Program: VEGA
Project leader: Ing. Sulová Zdena DrSc.
Annotation: The development of multidrug resistance in neoplastic cells results frequently from overexpression of the transport ATPase of the plasma membrane – P-glycoprotein (P-gp), which ensures an effective removal of hydrophobic substances from the intracellular space. P-gp is a product of mdr1 gene and is a member of ABC (ATP binding cassette) transporters. Several studies have shown that P-gp overexpression is accompanied by structural changes in the cellular architecture (increase in cell volume, cell surface corrugation, higher formation of caveolae, higher occurrence of intracellular vesicles, etc.). Structural changes at the level of plasma membrane are often associated with changes in surface saccharides as expressed in altered intensity and characteristics of lectin binding, of ruthenium red staining or binding of antibodies. P-gp overexpression is accompanied by increased production of a calcium binding protein – sorcin. Calnexin – a molecular chaperon of endoplasmic reticulum plays probably an important role in P-gp orientation and insertion during its maturation process. The present project will aim at the study of these phenomena by means of electron microscopy, immunochemistry and immunocytochemistry.
Duration: 1.1.2007 – 31.12.2009
Regulácia Na+/Ca2+ výmenníka za normálnych a patologických podmienok v srdci a mozgu cicavcov
Regulation of the Na+/Ca2+ exchanger under normal and pathophysiological conditions in the heart and brain of mammals
Program: VEGA
Project leader: RNDr. Hudecová Soňa CSc.
Annotation:
Duration: 1.1.2007 – 1.12.2009
Štruktúra, funkcia a regulácia neuronálnych vápnikových kanálov
Structure, function and regulation of neuronal calcium channels
Program: VEGA
Project leader: doc. RNDr. Lacinová Ľubica DrSc.
Annotation: Structure and function of neuronal calcium channels will be studied with emphasis on the T-type calcium channel. Mechanism of their regulations by transmembrane voltage and/or by intracellular signaling pathways still remains partly unknown. We will characterise their ion selectivity and permeability, kinetics of activation, inactivation and deactivation and the influence, which have on these parameters charged residues in transmembrane segments S4, which form putative voltage sensors. Furthermore, contribution of cysteine residues to stabilisation of tertiary channel structure will be investigated. For these experiments we will construct series of point mutants of the Cav3.1 channel. We will also investigate regulation of neuronal calcium channels by phoshorylation. Most of experiments will employ HEK 293 cell line transiently transfected with various channel constructs.
Duration: 1.1.2007 – 1.12.2009
DNA diagnostika závažných dedičných ochorení, častých v populácii Slovenska
DNA diagnostics of serious genetic disorders, frequent in the Slovak population
Program: Iné projekty
Project leader: prof. RNDr. Kádaši Ľudevít DrSc.
Annotation: Genetic disorders represent a serious burden, both in medical and social terms, for their high contribution to human morbidity and mortality. Due to new achievements in the research of human genome, possibilities of etiopathogenic diagnosis and genetic prognosis (genetic counselling, pre-symptomatic screening, prenatal diagnosis) of these disorders have dramatically improved. In this process identification of disease causing mutation is of decisive significance. This project is aimed at developing sensitive, reliable, rapid, and cost effective methods for mutation identification for early clinical and prenatal diagnosis of serious genetic disorders as cystic fibrosis, phenylketonuria and degenerative neuro-muscular disorders, frequent in the population of Slovakia
Duration: 1.1.2008 – 31.12.2008
Spriahnuté vrátkovanie RYR2 kanálov izolovaných zo srdca potkana
Coupled gating of RYR2 channels from rat heart
Program: VEGA
Project leader: Mgr. Gaburjáková Marta PhD.
Annotation: The rhythmic activity of the heart is connected to periodically repeating Ca2+ influx and Ca2+ efflux into and from sacoplasmic reticulum (SR) of muscle cells. In cardiac muscle, massive Ca2+ release from the SR is mediated by ryanodine receptor / Ca2+ channel type 2 (RYR2). This global process is the result of summation of brief and local Ca2+ release events that are intrinsically self-regenerative. This property requires existence of a strong termination mechanism what stops Ca2+ release and allows muscle to relax. Till now several models for Ca2+ release termination have been suggested, however no one has been experimentally proved and widely accepted by scientific community. One of the latest models is the mechanism of coupled gating of RYR2 channels. Two or more RYR2 channels open and close simultaneously giving the visual impression of one ion channel with double or multiple conductance. This model considers allosteric interactions among several ion channels resulting in induced synchronous gating. Although the existence of coupled RYR2 channels has been proved on experimental level, the molecular nature of this phenomenon remains to be elucidated. The main aim of our work is to contribute to the deeper understanding of this important phenomenon. We will employ the method of reconstitution of RYR2 channels into artificial lipid membrane. This method provides detail information about functional properties of ion channels by observing electrical current (~pA) flowing through these channels.
Duration: 1.1.2006 – 31.12.2008
Kam siahajú naše genetické korene: Fylogeografická analýza variability mitochondriálnej a Y-chromozómovej DNA v slovenskej populácii
Tracing our genetic roots: A fylogeography of mitochondrial and Y-chromosomal DNA variability in Slovak population
Program: VEGA
Project leader: prof. RNDr. Kádaši Ľudevít DrSc.
Annotation: Specific and very advantageous features of haploid DNA markers from the human mitochondriel DNA (mtDNA) and Y-chromosomal DNA (Y-DNA) make it possible to reconstruct the peopling of different geographic areas as wellas to trace past population migrations and other population movements, making use of the present-day distribution of these markers in the populations concerned. Most important of these specific features are uniparental inheritance of these DNA moleculesm their lack of genetic recombination, and relevant mutation rates. In the course of last 10 years, the analysis of the mtDNA and Y-DNA variability was performed in a number of different poulations of all continents, and often brought new and unexpected information on their population histories. The proposed project aims at performing a detailed analysis of mtDNA and Y-DN variability in Slovak population (including Slovak Roms) and at contributing in this way to the knowledge of history and pre-history of peopling of this part of Central Europe
Duration: 1.1.2006 – 12.12.2008
Fenotyp "multidrug" rezistencie spojený s overexpresiou mdr 1 – p-glykoproteínu v neoplastických bunkáchp
Phenotype of multidrug resistance associated with overexpresion of mdr 1 – p-glycoprotein in neoplastic cells
Program: VEGA
Project leader: doc. Ing. Breier Albert DrSc.
Duration: 1.1.2006 – 1.12.2008
Komplex I a dýchací reťazec trypanozomatíd
Complex I and respiratory chain of trypanosomatides
Program: VEGA
Project leader: Mgr. Valachovič Martin PhD.
Annotation: The project is aimed at the the analysis of the antimycotic substances that affect various processes linked to functions and biogenesis of membrane lipids in the yeast Saccharomyces cerevisiae: terbinafine (inhibitor of ergosterol synthesis on the level of squalene epoxidation), amphotericin B (memrane active substance forming complexes with ergosterol) and cerulenin (inhibitor of fatty acid synthesis). The general emphasis is given to the effects of specific processes influenced by the antimycotics on general lipid homeostasis in yeast cell and on functions of cell membranes. Particular problems studied in the project are the biogenesis of lipid particles (e.g. squalene accumulation after terbinafine treatment, regulation of triglyceride synthesis in cerulenin-treated cells) and the dynamics of membrane domains (rafts) in cells treated with amphotericin B. The specific effects of terbinafine, amphotericin B and cerulenin on membrane biogenesis are studied with the focus on the antimycotic effect of these substances.
Duration: 1.1.2006 – 1.12.2008
– – Mitochondriálne interakcie v evolúcii, speciácii, starnutí a eukaryotickej harmónii. (Mitofylogenomika a mitochondriálne inžinierstvo)
Mitochondrial interactions in the evolution, speciation, ageing and eukaryotic harmony /mitophylogenomics and mitochondrial engineering/
Program: VEGA
Project leader: RNDr. Hapala Ivan CSc.
Duration: 1.1.2006 – 1.12.2008
Molekulárne a funkčné aspekty modulácie inozitol 1,4,5- trisfosfátových receptorov v normálnych a patologických podmienkach
Program: VEGA
Project leader: prof. Ing. Križanová Oľga DrSc.
Duration: 1.1.2006 – 1.12.2008
Produkcia a využitie monoklonových protilátok pri biochemickej, histochemickej a funkčnej analýze niektorých CD molekúl (antigénov) bunkových membrán hovädzieho dobytka
Production and application of monoclonal antibodies in biochemical, histochemical and functional analysis of some CD molecules (antigens) of bovine cell membranes
Program: VEGA
Project leader: Ing. Simon Michal DrSc.
Annotation: Cell membrane molecules (CD antigens) represent an important part of immune mechanism of organism. It has been shown that the monoclonal antibodies are a useful tool in recognition, and biochemical and functional characterization of these molecules. Suggested project is focused on the production, cytometrical, biochemical and histochemical analysis of monoclonal antibodies (mAbs) specific for leukocyte (CD antigens) and sperm antigens of cattle. Monoclonal antibodies specific for leukocyte antigens will be used to study local immunity of mammary gland of dairy cows. The antigens of bull spermatozoa will be analysed by mAbs specific for sperm antigens.
Duration: 1.1.2006 – 1.12.2008
Reakcia cytoarchitektúry svalových buniek na zablokovanie expresie špecifických proteínov
Respons of the cytoarchitecture of muscle cells to invalidation of the specific proteins expresion
Program: VEGA
Project leader: RNDr. Novotová Marta CSc.
Annotation: By applying a new stereological approach to quantification of cytoarchitecture we have characterized the plasticity of muscle cells in specific animal models. Analyses of the effects of blocking the expression of selected proteins on the ultrastructure of myocytes provided a new view on the relationship between cytoarchitecture and function. We have shown that blocking the expression of different muscle proteins leads to profound changes in the cytoarchitecture that, together with molecular adaptation mechanisms, participate on the overall changes in cell function. Comparison of changes in the cytoarchitecture with those of energy transport, electrical and contractile activity of myocytes points to a close relation between cytoarchitecture, energetics, and contractility of the cell. Quantification of cell ultrastructure produced a large amount of data that asked for development of software for creation of geometric models of myocytes to improve communication of the findings and to test structural hypotheses.
Duration: 1.1.2006 – 1.12.2008
Štúdium modulácie chloridových a vápnikových kanálov v mitochondriálnych membránach srdca potkana
Study of modulation of chloride and calcium channels mitochondrial membrane of rat heart
Program: VEGA
Project leader: RNDr. Ondriaš Karol DrSc.
Duration: 1.1.2006 – 1.12.2008
Štúdium transformácie energie u methanoarchaea Methanothermobacter thermoautotrophicus: izolácia a charakterizácia mutantov rezistentných k amiloridu, NO3, DCCD a bafilomycínu A1
Study of energy transformation in methanoarchaea Methanothermobacter thermoautotrophicus: Isolation and characterization of amiloride, NO3, DC CD and bafilomycín A1- resistant mutants
Program: VEGA
Project leader: Doc. RNDr. Šmigáň Peter DrSc.
Annotation: The methanogenic archaea are a group of strictly anaerobic microorganisms producing methane. The bioenergetics of methanogenesis has unique features. In the process of methanogenesis , its redox reactions are coupled with formation of H+and Na+ electrochemical gradients which drive ATP synthesis in these cells. In spite of many studies over the past decade these processes have not yet been satisfactorily elucidated.To better understand the function and relationship of H+ and Na+ energetic subsystems, in 1997 , a project to use biochemical mutants in the study of energy conservation in methanoarchaea was outlined This approach was suggested since efficient genetic manipulation systems is missing for thermophilic methanoarchea.This approach has resulted in the isolation and characterization of several mutants resistant to the relevant inhibitors of energy machinery. Spontaneous mutants of M.thermautotrophicus resistant to amiloride ( Na+/H+ antiporter inhibitor- an important molecular device responsible for coupling of proton and sodium ions cycles)with a defect in Na+/H+ antiporter and NO3- resistant mutant ( A1A0 ATP synthase inhibitor) were isolated and partly characterised. An additional study of amiloride resistant mutant can contribute to the understanding of a function of this antiporter in energetics of methaoarchaea. So far, ion specifity for A1A0 ATP synthase was not in methanoarchaea settled. The physiology and bioenergetics of methanoarchaea indicate that both ions – H+ or Na+ might be coupling ions.In silico analyses suggest that A1A0 ATP synthase most likely use Na+ as coupling ions. The study of NO3- resistant mutant could contribute to the elucidation of this complex situation . Besides, in this project we shall try to isolate and characterize new mutants resistant to DCCD and bafilomycin A1 which are inhibitors of membrane part A0 of A1A0 ATP synthase . Such an outlined project could contribute to the elucidation of Na+/H+ antiporter function in energetics of methanogens and to the understanding of molecular mechanisms of the energy coupling in methanoarchaeaThe results were published as the 5 research articles in international scientific journals, and presented as 13 lectures and posters at national and international scientific conferences.
Duration: 1.1.2006 – 1.12.2008
Vývin reprodukčnej schopnosti prepelice japonskej v simulovanej mikrogravitácii
Development of reproductive ability in Japanese quail exposed to simulated microgravity
Program: VEGA
Project leader: Ing. Škrobánek Peter CSc.
Annotation: The project represents a continuation of our recent research of postnatal development of Japanese quail in conditions of simulated microgravity – hypodynamia.The objective of this project is to studey the effects of chronic hypodynamia on the sexual development of male and female Japanese quail from hatch to 70 days of age. The developmental differences of reproductive ability between the quail exposed do hypodynamia and control birds reared in standard conditions will by studied by morphometrical and physiological methods. The obtained data will be utilized in future experiments concerning quail ontogeny in the real weightless environment – microgravity.
Duration: 1.1.2006 – 1.12.2008
CalSigHF – Zmeny cytozolickej a luminálnej vápnikovej koncentrácie pri zlyhaní srdca
Abnormal cytosolic and luminal calcium signalling in heart failure
Program: APVV
Project leader: Ing. Zahradníková Alexandra DrSc.
Annotation: Heart failure (HF) is a leading cause of morbidity and mortality and a major health care problem in the Western world. In HF a progressive weakening of cardiac contractile performance leaves the heart unable to pump blood through the body. The cellular and molecular defects that cause depressed contractility of failing myocytes are not well understood but seem to culminate in abnormal sarcoplasmic reticulum uptake, storage and release. The overall goal of this proposal is to understand the mechanism responsible for abnormalities of Ca handling by the main Ca storage organelle, the sarcoplasmic reticulum, in HF. Specifically, the project will focus on Ca signaling inside this delicate membrane-bound intracellular structure and address its importance for the defective cytosolic Ca handling in HF. To accomplish this goal a combination of confocal imaging and electrophysiological approaches to simultaneously monitor luminal and cytosolic levels of Ca will be used together with the biochemical technique of Western blot. The studies will be performed in three different animal models of HF. These studies will contribute to better understanding of the underlying causes of HF and facilitate the development of rational strategies to treat this disease.
Duration: 1.1.2007 – 30.11.2008
BIOMEMBRÁNY: Prierezový program vzdelávania doktorandov a mladých vedeckých pracovníkov v biologických a biomedicínskych odboroch
BIOMEMBRANES: cross-sectional educational program for graduate students and young scientists in life sciences
Program: Európsky sociálny fond /ESF/ (MŠ SR, MPSVR SR)
Project leader: RNDr. Hapala Ivan CSc.
Project web page: http://www.ubgz.sav.sk/biomembrany/index.htm
Duration: 1.2.2006 – 31.10.2008
Vzdelávanie a podpora postdoktorandov – mladých vedeckých pracovníkov v oblasti vied o materiálovom inžinierstve, v chemických vedách a v oblasti molekulárnej biológie a genetiky, vrátane biotechnológií
Education and support of postdoctoral students – young researchers in field of material engineering science, chemical science and molecular biology and genetics, including biotechnologies
Program: Európsky sociálny fond /ESF/ (MŠ SR, MPSVR SR)
Project leader: Mgr. Niederová Ľubica PhD.
Annotation:
Duration: 1.7.2007 – 30.9.2008
– – Súčasné trendy vo fyziologickom a behaviorálnom výskume – rozširovaním praktických zručností k vyššej efektivite doktorandského štúdia
Current trends in physiological and behavioural research – higher effectiveness of doctoral studies by widening the practical skills
Program: Európsky sociálny fond /ESF/ (MŠ SR, MPSVR SR)
Project leader: RNDr. Košťál Ľubor CSc.
Duration: 1.11.2006 – 31.7.2008
Kvasinky ako model patologických porúch lipidovej homeostázy eukaryotických buniek
Yeast as a model of pathological disturbances of eukaryotic lipid homeostasis
Program: APVV
Project leader: Mgr. Valachovič Martin PhD.
Duration: 1.2.2005 – 31.12.2007
Mechanizmus väzby excitácie s kontrakciou v normálnom a zlyhávajúcom myokarde cicavcov
Mechanism of excitation-contraction coupling in normal and failing mammalian myocardium
Program: APVV
Project leader: RNDr. Zahradník Ivan CSc.
Annotation: Excitation-contraction coupling in cardiac myocytes is mediated by calcium signalling in the tubulo-reticular junction, which includes calcium influx from the extracellular environment, calcium release from the sarcoplasmic reticulum, and inactivation of both processes. In failing heart, contractility of myocytes is impaired due to a decrease in calcium release. The aim of this proposal is to define the relationship between the organization of the tubulo-reticular junction and calcium signalling in normal and failing heart. We will employ our well-established methodological and theoretical approaches (measurement of pure calcium currents and local calcium signals, stereological analysis of the environment of organelles, modelling of reaction-diffusion processes, simulation of calcium channel activity in the tubulo-reticular junction, and geometrical modelling) that make possible to characterize the organization of the tubulo-reticular junction and calcium signalling among calcium channels.
Duration: 1.2.2005 – 31.12.2007
molgen – Molekulárno genetické princípy membránovo viazaných procesov buniek v normálnej a patologickej fyziológii živočíchov
Molecular genetic principles of membrane bound processes in normal and pathological animal physiology
Program: APVV
Project leader: Doc. RNDr. Šmigáň Peter DrSc.
Annotation: Proposed project represents a continuation of the preceding APVT project. Partial goals of the project can be summarised as follows: a/ the study of the energy transformation in Methanoarchaea using a set of specific mutants; b/ the study of the membrane homeostatic mechanisms from the point of view of biogenesis and turnover control of membrane phospholipids and sterols and the study of the protective effects of the natural antioxidants during membrane damage; c/ the study of the involvement of selected signal molecules (leptin, dopamine) and their membrane receptors in control mechanisms important from the point of view of poultry production and welfare; d/ the study of the CD molecules of the cell membranes in blood cells and spermatozoa of cattle using monoclonal antibodies.
Duration: 1.2.2005 – 31.12.2007
Signalizačné a transportné funkcie biologických membrán za normálnych a patologických podmienok
Program: APVV
Project leader: RNDr. Ondriaš Karol DrSc.
Duration: 1.2.2005 – 31.12.2007
Fyziológia správania hydiny vo vzťahu k produkčným vlastnostiam a welfaru
Behavioural physiology of poultry related to production traits and welfare
Program: VEGA
Project leader: RNDr. Bilčík Boris PhD.
Annotation: The aim of the project is to study the problems of behavioural physiology related to current welfare problems in poultry kept for meat and egg production. Following models will be studied: the effects of food restriction on physiology and behaviour of broiler breeder hens, the relation between aggressive behaviour, sexual behaviour and dopaminergic neurotransmission in broiler breeder males and the neurophysiological control of feather pecking in laying hens. Another aim of the project is the validation of the radiotelemetric measurement of blood pressure, heart rate, body temperature and biopotentials from the point of view of the potential use for the measuring and monitoring of poultry welfare.
Duration: 1.1.2005 – 1.12.2007
Vápniková homeostáza a signalizácia v bunke – vzájomné vzťahy a štruktúry, funkcie a metabolizmu pri rozvoji patologickej zmeny
Calcium homeostasis and signalization in cells – structural, functional and metabolic relations during developmentof patologic changers
Program: APVV
Project leader: MUDr. Uhrík Branislav CSc.
Duration: 1.1.2005 – 1.12.2007
Transportné a signalizačné mechanizmy biologických membrán za normálnych a patologických podmienok
Program: APVV
Project leader: RNDr. Ondriaš Karol DrSc.
Duration: 1.10.2002 – 31.12.2006
Membrproc – Membránovo viazané procesy a ich úloha v normálnej a patologickej fyziológii hospodárskych zvierat a ich symbiotických mikroorganizmov
Membrane-associated processes and their role in normal and pathological physiology of farm animals and their symbiotic microorganisms
Program: APVV
Project leader: Doc. RNDr. Šmigáň Peter DrSc.
Annotation: Project proposal is aimed at the understanding of the roles of selected membrane-associated processes in the physiology and pathophysiology of farm animals and their symbiotic microorganisms To contribute to the understanding of structural and functional interactions of membrane-bound processes effective on various levels of biological organization in the physiology of economically important animals and their symbiotic microorganisms
Duration: 1.10.2002 – 31.12.2005
RyR – Štúdium modulácie vlastností vnútrobunkových kanálov v mitochondriách a v endoplazmatickom retikule buniek
Study of modulation of intracellular channels from mitochondria and endoplasmic reticulum
Program: VEGA
Project leader: RNDr. Ondriaš Karol DrSc.
Duration: 1.1.2003 – 31.12.2005
RyR – Štúdium modulácie vlastností vnútrobunkových vápnikových kanálov z buniek kardiomyocytov a trachey
Study of modulation of intracellular calcium channels from cardiocytes and trachea
Program: VEGA
Project leader: RNDr. Ondriaš Karol DrSc.
Duration: 1.1.2000 – 31.12.2002
IP3R – Vplyv farmakologicky aktívnych látok na vlastnosti inozitol 1,4,5-trifosfátom riadeného jednotlivého vápnikového kanálu.
Influence of pharmacologically active drugs on properties single IP3R channels
Program: VEGA
Project leader: RNDr. Ondriaš Karol DrSc.
Duration: 1.1.1997 – 31.12.1999
Obranné mechanizmy neoplastických buniek proti chemickému stresu
Defense mechanisms of neoplastic cells against chemical stress
Program: APVV
Project leader: Ing. Sulová Zdena DrSc.
Annotation: Animal cells are disposing with large spectrum of defense mechanisms against damage induced by cytotoxic agents. These mechanisms are based on: i) ability of detoxification enzymes to modify the structure of cytotoxic agents; ii) ability of plasma membrane specialized transporters to eliminate the drugs from cell\’s intracellular space; iii| changes in expression of cytotoxic agents target proteins; iv| changes in regulatory pathways responsible for initiation of programed cell death mechanisms as response of cell damage induced by cytotoxic agents. Initiation of these mechanisms in neoplastically altered tissue leads to multidrug resistance (MDR) development. Reduced cell sensitivity to large group of structurally unrelated anticancer drugs with different mechanisms of pharmacological action is feature typical for MDR. If MDR is developed in cancer tissue, it represents real obstacle of effective chemotherapy. MDR could develop in cells of alla types of solid malignant tumors and also in blood malignancies. MDR development could be considered as adaptation of neoplastic cells on previously applied chemotherapy cycles. However, MDR could be present in neoplastic cells of patients that were not treated by anticancer drugs. MDR in this case represents specific phenotype of neoplasticaly altered cells. Targeted research on this topic represents aim of this project.
Duration: 1.7.2016 – 0.0.0000