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A Szentágothai János Kutatóközpont a PTE korszerű, nemzetközi tudományszervezési és menedzsment normák szerint kialakított új intézménye, amely az élettudományi, élettelen természettudományi, valamint környezettudományi oktatás...

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Research portfolio

R&D results

Research concept

Temporal lobe epilepsy (TLE) is one of the most common neurological disorders.  A significant portion of cases do not respond to drug therapy, constituting a major decrease in quality of life for patients.  During seizures, certain parts of the brain produce recurrent, over-synchronized brain rhythms, and typically the more the pathological oscillation spreads throughout the brain, the more severe the symptoms are. In temporal lobe epilepsy, seizures start in a brain region that is responsible for memory and navigation. Therefore, TLE patients also suffer from memory and navigation deficits, further emphasizing the need for new treatment strategies.

While much research on genetic and cellular factors underlying epilepsy is currently underway, fewer studies have investigated how the timing of activity in certain building blocks—the neurons—of the brain change in epileptic patients, especially before and during seizures.  The scope of our research is to learn how individual neurons change their rhythmic activities in epilepsy and importantly, how their connectivity is altered compared to healthy neuronal networks. Until recently, technical limitations prevented the collection of these data without disrupting the activity of individual cells with invasive measurements. It is critical to understand both the normal activity of these brain areas and how certain neuronal cell types may suddenly convert these normal rhythms into an uncontrollable synchronous discharge pattern.
In vivo juxtacellular/ in vitro patch-clamp/optogenetic methods are used in the laboratory in order to interrogate the roles of diverse neuronal types in seizure generation. The outcome of our research will potentially help to develop novel epilepsy treatment paradigms which intervene in seizure generation time specifically rather continuously like an oral medication, helping to decrease long lasting effects of medication on normal brain function.

more at www.vargalab.com

Laboratories, instruments

please visit www.vargalab.com

Services

R&D results

Research concept

Despite the advances in the treatment of heart failure over the past decades, this condition represents an enormous public health burden. Considering this unmet clinical need, the elucidation of novel mechanisms involved in heart failure pathogenesis holds the promise of developing new therapies for this prevalent and deadly disease. We focus on protection and regeneration of the diseased heart utilizing multidisciplinary approaches. We envision to translate the findings obtained in preclinical studies (in vitro and ex vivo models, in vivo preclinical small-animal models and clinically relevant large-animal models) toward clinical application or vice versa, from clinical observations back to mechanistic insights. The primary interests of our research group are in the following areas:

Preclinical studies:

  • Identification of novel cardiokine systems regulating cardiac homeostasis (e.g. cardiac function, metabolism, and cell survival) under physiological conditions.
  • Elucidation of cross-talk between cardiac non-myocytes (e.g. fibroblasts) and cardiomyocytes regulating cardiac growth and cell survival during cardiac remodeling.
  • Development of novel small-animal models of heart failure.
  • Establishment of novel large-animal models of heart failure.
  • Establishment of cardiac PET-MRI in large-animal models of heart failure to measure simultaneously left ventricular function, structure, and metabolism (in cooperation with the University of Kaposvár).
  • Proof of concept studies on the beneficial therapeutic effects of intramyocardial delivery of cardiokines in combination with miRNAs and lncRNAs (e.g. impact on cardiac hypertrophy, cell survival, cardiac regeneration, metabolism, angiogenesis, interstitial fibrosis, underlying signaling mechanisms [e.g. epigenetic changes, chromatin remodeling, etc]) in small- and large-animal models of heart failure.

Clinical studies:

  • Identification of novel tissue-specific biomarkers (cardiokines, microRNAs, lncRNAs) for improved prediction of outcome in acute myocardial infarction.
  • Identification of new tissue-specific biomarkers (cardiokines, microRNAs, lncRNAs) to improve risk stratification for cardiac resynchronization therapy in heart failure.

Laboratories, instruments

  • Langendorff-type isolated heart perfusion system (MDE Research) for ex vivo evaluation of rat/mouse cardiac function.
  • EPIQ7 Live 3D echocardiograph (Philips) for small- and large-animal models of heart failure.
  • NOGA® system (Biosense Webster, Cordis, Johnson & Johnson) for electromechanical mapping and transendocardial injections in large-animal models of heart failure.
  • Magnetom Avanto 1,5T cardiac MRI (Siemens), and Biograph 3T cardiac PET-MRI (Siemens) for large-animal models of heart failure (in cooperation with the University of Kaposvár).

Services

  • Development of novel small- and large-animal models of heart failure.
  • Cardiac PET-MRI studies in large-animal models of heart failure (in cooperation with the University of Kaposvár).
  • Testing novel lead compounds in small- and large-animal models of heart failure.

R&D results

Research concept

The limbic system plays pivotal role in the maintenance of homeostasis and regulation of motivation, emotion, learning and memory processes. Our investigations aim to unravel new limbic forebrain neuronal and neurohumoral mechanisms of the central homeostatic control in healthy and disease state conditions using multidisciplinary approaches such as in vivo microelectrophysiology, combined behavioral-neurochemical paradigms, molecular biology, transgenic technology, immunohistochemistry and single molecule imaging. In addition to elucidate new regulatory processes and so far unknown pathomechanisms, we believe that our research approach enables us to identify new molecular targets in the brain and opens new avenue in development of novel lead compounds. We place particular emphasis on investigations exploring the effect of steroid hormones in the basal forebrain in physiological and neurodegenerative processes. In these experiments, we study the neuroprotective effect of estrogen in basal forebrain cholinergic neurons in Alzheimer’s disease using single molecule detection microscopy and transgenic technology.

Laboratories, instruments

Olympus fiber total internal reflection fluorescence microscope for single molecule detection.

Services

  • Development of novel in vivo microelectrophysiological and neurochemical examination techniques
  • Development of single molecule detection microscopy systems

R&D results

1. Patents:

Waczek F, Helyes Zs, Őrfi L, Kéri G, Szűts T, Pintér E, Szolcsányi J, Szőke É. New agents for treating neurogenic inflammation and neuropathic hyperalgesia related disorders. 2014. Hungarian and USA PCT P1400432 (University of Pécs and Vichem Ltd.)

Helyes Zs, Matyus P, Tekus V, Scheich B. Semicarbazide-sensitive amine-oxidase inhibitors, as analgesics in traumatic neuropathy and neurogenic inflammation. 2014. Hungarian and USA PCT P1400205 (University of Pécs).

G. Pozsgai, E. Pintér, M. Boros, L. Nagy, G. Nagy: H2S sensor for in vivo measurements. 2013. Reg. No.: U1200173 (University of Pécs)

 

2. Industrial Collaborations:

  • Pharmnovo Ltd. – Bengt von Mentzer, migraine, pain
  • Soft Flow Hungary – microcirculation
  • Varga Herb Manufactory – inflammation models
  • Richter Gedeon Plc.-Establishing and validating model systems for the investigation of the trigeminovascular activation

Research concept

Complex analysis of the role of capsaicin-sensitive afferents, the released neuropeptides and their receptors, as well as the pathophysiological importance of neuro-immune interactions in complex animal models of pain, inflammation, and tumor development. Identification of new pharmacological targets and preclinical investigation of analgesic and anti-inflammatory drug candidates in these systems.

  • Acute and chronic joint inflammation: Mouse/rat models of arthritis (kaoline, carrageenan-induced acute monoarthritis, complete Freund’s adjuvant-induced chronic polyarthritis, autoantibody-transfer and proteoglycane-induced polyarthritis, iodoacetate-induced osteoarthritis).
  • Acute and chronic airway inflammation: Mouse models (endotoxin-induced non-allergic and dust mite antigen-induced allergic lung inflammation, ovalbumine-induced asthma, cigarette smoke-evoked chronic bronchitis).
  • Acute and chronic cutaneous inflammation: mouse/rat models (irritant-induced acute inflammation, oxazolone-evoked allergic contact dermatitis, murine psoriasis models, bleomycine-induced scleroderma-model).
  • Chronic gastric and bowel inflammation: Mouse models of inflammatory gastrointestinal conditions (gastritis, autoimmune colon inflammation, Crohn-disease models).
  • Migraine and chronic neuropathy: Mouse/rat models of traumatic mononeuropathy, diabetic polyneuropathy, toxic polyneuropathy, and bone metastasis-induced neuropathic pain.

Laboratories, instruments

Intravital and surgical videomicroscope with camera and image analysis software: With the aid of ex vivo or in vivo labeling techniques vascular responses and the movement of labeled immune cells can be visualized, quantified, and monitored in real time. The technique is suitable to examine the surface of organs in situ.

Further informations about the instrument:

 

Pericam PSI laser speckle imager, PIM-II laser Doppler scanner, Periflux 5000 laser Doppler perfusion monitor (Perimed): Continous visual monitoring and precise quantification of skin, joint, and brain microcirculation. Suitable for both preclinical models and clinical studies.

Further informations about the instruments:

 

Micro-Computer Tomograph (Bruker): High resolution CT-imaging of anesthetized rodents (inbuilt cardiac and respiratory monitoring), excised organs, and tissue samples. Structural examination of various organic/inorganic materials is also possible. Enables long term follow-up of disease models in the same set of subjects. Particulary suitable for in vivo structural imaging studies (bone remodeling, lung architecture).

Further informations about the instrument:

 

Luminescent-fluorescent imaging workstation (Perkin-Elmer): Bioluminescent/fluorescent in vivoimaging enables the examination of the expression of proteins, receptors, and enzymes, production of free radicals in murine models. Luminescent imaging utilises either free radical-specific chemiluminescent substrates, or light emitted during the luciferase-luciferin enzyme reaction. During fluorescence imaging studies specific dyes and fluorescent probes are used. The instrument is capable of imaging in vivo(mice/rats), ex vivo (organ and tissue samples), or in vitro (e.g. cell cultures) samples.

Further informations about the instrument:

 

Fluorescence Molecular Tomograph (Perkin-Elmer): The instrument is capable of monitoring diverse mouse disease models using dedicated fluorescent near-infrared contrast agents (excitation at 680 or 750 nm wavelengths). Possible areas of use are: inflammatory/tumor-induced vascular leakage, receptor expression pattern, inflammatory enzyme activity, bone remodeling, etc. The same set of mice can be examined repeatedly in a noninvasive manner. The instrument is capable of 3D reconstruction of fluorophore distribution, and absolute (picomolar) quantification of the amount of fluorescent probes. Combination of fluorescent tomographic and structural CT-scans (multimodal image reconstruction) is also possible.

Further informations about the instrument:

Services

Complex pharmacological investigations in acute or chronic mouse models of painful/inflammatory conditions using functional, morphological, immunological, and imaging techniques. Examination of complex pathophysiological processes and integrative analysis of the effects of drug candidates in vivo and in vitro.

 

1.) Fluorescent and luminescent functional imaging of living, anesthetized mice/rats, excised tissue samples, and cell cultures

Analysis of the expression and distribution of various biological markers (enzyme activity, receptors, structural components, free radicals) using fluorescent contrast agents, and bioluminescent/chemiluminescent substrates.

Instruments:

  • PerkinElmer FMT 2000 – Fluroescent molecular tomography system
  • PerkinElmer Lumina II - Luminescent/fluorescent imaging system

Earlier contract/cooperation: Scientific collaborations with the Institute of Physiology, Semmelweis University, and the Institute of Experimental Medicine, Hungarian Academy of Sciences

Contact: Prof. Dr. Zsuzsanna Helyes, zsuzsanna.helyes@aok.pte.hu, +36 72/501-500/35591 or +36 72/501-500/29043

 

2.) Intravital microscopy examinations

Real time monitoring of vasodilation, plasma protein extravastion, leukocyte accumulation, etc. in murine inflammation models. Imaging and quantitative analysis of these parameters in the skin, brain surface, joints, and internal organs.

Instruments:

  • NIKON intravital microscope with camera and image analysis software

Contact: Prof. Dr. Zsuzsanna Helyes, zsuzsanna.helyes@aok.pte.hu, +36 72/501-500/35591 or +36 72/501-500/29043

 

3.) In vivo imaging of microcirculation in mice/rats, large animals and humans (skin, mucous membrane)

Measurement of microcirculation in animal models of inflammation, vasoregulatory disorders, and migraine. Noninvasive investigation of local skin blood flow in human subjects.

Instruments:

  • PeriScan PIM II laser Doppler imager with inbuilt blood flow sensor
  • PeriFlux 5000 Laser Doppler Flowmeter – monitoring of microcirculation and PO2/PCO2. Optional application of temperature and pressure stimuli.
  • PeriCam laser speckle imager – Capable of monitoring rapid/transient changes of microcirculation

Earlier contract/cooperation:

  • Soft-Flow Ltd.,
  • Richter Gedeon Plc.,
  • University of Szeged, Dept. of Neurology

Contact: Prof. Dr. Zsuzsanna Helyes, zsuzsanna.helyes@aok.pte.hu, +36 72/501-500/35591 or +36 72/501-500/29043

R&D results

Research concept

Laboratories, instruments

Services

R&D results

Research concept

1. Retinal signalization team: Dr. Róbert Gábriel, Andrea Kovács-Valasek

Our research focus is to expand our knowledge on the mechanisms of metabolic retinal degenerations by exploiting experimental work with animal models. We explore how metabolic mechanisms that mediate human retinal degenerations induce retinal cell loss, and which biochemical signaling pathways are involved in mechanisms that eventually impair vision. Our results will reveal the potential rescue mechanisms to avoid retinal degeneration by blocking the degeneration pathways or by enhancing mechanisms that serve neuronal protection. The knowledge on this latter issue will allow us to test and design new pharmacological compounds. Throughout these experiments we will also gain information on the mechanisms of retinal information processing, neuronal degeneration and neuronal protection.

2. Retinal electrical synapses team: Dr. Béla Völgyi, Dr. Tamás Kovács-Öller, Gábor Debertin, Alma Ganczer, Ádám Tengölics, Márton Balogh, László Albert

Over 85% of the information perceived by our nervous system is processed by the retina, thus it is essential to understand how the retinal neuronal hyper-network works. Electrical synapses have been known for some 40 years, however their crucial role in visual information processing has only become obvious in recent years. Our team performs experiments to show that electrically coupled retinal neuronal networks play important roles in higher visual functions. We examine the expressional changes of the gap junction forming connexin proteins during the postnatal development and/or induced by changes in the environment. Our work particularly focuses on those inner retinal gap junctions that are formed by ganglion and amacrine cells (ganglion-ganglion, amacrine-amacrine and amacrine-ganglion) and participate in the synchronization of ganglion cell action potentials. We study how such ganglion cell population activity encodes certain visual patterns or visual cues. We also study how the function of electrical and chemical synapses affect each other and if they interfere and/or cooperate to serve signaling. Results of our research will contribute to algorithms for the stimulation of retinal prostheses and/or to provide data to design high performance bionic eyes for robotics.

Laboratories, instruments

  • Molecular neurobiology laboratory (Western-blot, RT-PCR, qPCR)
  • Histology lab (microtomes for light- and electron-microscopy, dissecting microscopes, digital photomicroscope)
  • Electrophysiology lab (3 electrophysiology setups; amplifiers (patch-clamp, extracellular AC, multielectrode MEA, horizontal electrode puller, micromanipulators, ant-vibration table, analog-digital converters, signal synchronization module etc.)
  • Ca++- imaging laboratory (2 TILL photonics system setups, Polychrome 5 monochromator light stimulators, Retiga2000 CCD camera, Andor895 camera, Nikon CCD camera)

Services

  • Histological, molecular biological and light- and electronmicroscopical examination of transmitters and their receptors
  • Histological and molecular biological examination of apoptotic mechanisms
  • Imaging experiments (Ca++- imaging)
  • Extracellular electrophysiological recordings
  • Multielectrode extracellular recordings
  • Patch-clamp electrophysiological recordings

R&D results

Research concept

Studying stress-induced structural and functional alterations in animal models for neuropsychiatric disorders

The physiological stress response is essential for our daily survival and helps us to adapt to the ever changing environment. However, sustained uncontrollable stress can induce various dysfunctions and pathological alterations in our body. Our key interest is the structural plasticity of the brain in relation to stress.

We focus on stress-induced changes in neuronal plasticity affecting neuronal networks, adult neurogenesis as well as glial changes in the hippocampus and neocortex. We hypothesize that such stress-induced structural changes contribute to the pathophysiology of psychiatric disorders like depression or schizophrenia, but medications like antidepressant, antipsychotic treatment can also have influence. 

We aim for translational research using multidisciplinary methods ranging from molecular biology to in vitro and in vivo imaging.

Laboratories, instruments

MicroBrightField System (StereoInvestigator and Neurolucida) for post mortem quantitative histopathologica analysis. Nikon Eclipse Ti-U fluorescent microscope. Beckman CEQ 8000 genetic analysis system / DNA sequencer, QIA Cube for fully automated purification of DNA, RNA, or proteins, Liquid chromatography tandem mass spectrometry (LC/MS/MS), electrophoreses/blotting.

Services

Analysis of neurobiological changes related to depressive disorders in an animal model based on chronic behavioral stress and also clinal samples. We use of in vivo and post mortem imaging, and laboratory diagnostic tools searching for potential biomarkers.

R&D results

http://www.neurobio.pte.hu/kutatas/index.html

  • Development of tools and equipment for microelectrophysiology (from 1995).
  • Microelectrode development and testing (from 2000)
  • Software development for electrophysiology (from 2006)
  • Behavioral testing apparatus for measurement of thermal pain threshold (2007-2009)

Research concept

Cellularis neurophysiology:

Recording in vivo neuronal activity with microelectrodes int he rodent brain, iontophoretic application of neurochemicals, voltammetric detection of monoamine neurotransmitters.

Small animal behavioral physiology and psychopharmacology:

Psychopharmacology of the brain reward systems in rodents. Implementation of the delayed reward choice paradigm in computer controlled formal (operant) behavioral apparatus.

Human psychophysiology:

Psychophysiological and cognitive behavioral assessment of higher order brain functions such as perception, anticipation, reward devaluation, decision making. Recording behavioral and neurophysiological (EEG) correlates of somatosensory, auditory and visual stimulus identification and selection .

Laboratories, instruments

  • In vivo cellular laboratory: extracellular unit recording, stereotaxic apparaus, biollogical signal conditioning (amplifiers,filters, ADCs, measurement of voltage and current), constant current ganerators (for microiontophoresis).
  • Small animal behavior laboratory: general activity, open field test, elevated plus maze test, forced swim test, food-choice tests, computer controlled operant behavioral chambers, neurotoxic brain lesions, reversible brain inactivation, central/systemic administration of bioactive agents.
  • Human psychophysiology laboratory: high performance 32 channel biological amplifier (EEG, EMG, ECG, EOG), computer controlled behavioral apparatus. Current research 1) basic: neurophysiology of face perception; 2) applied: neurocognitve effects of non-ionising environmental electromagnetic fields.

Services

Applied systems neuroscience, drug development and validation

  • Development of novel testing techniques and methodology.
  • Development of novel equipment for testing.
  • Neurophysiological testing of bioactive environmental (chemical and electromagnetc) agents.
  • Research and development and formal education within the scope of the laboratory.

R&D results

  • Biobanking and Biomolecular Resources Research Infrastructure (BBMRI; www.bbmri.eu)
  • Ataxia Study Group (ASG), ERare3, EU7 network
  • Neuromix

Research concept

As a precursor of personalized medicine (P4 medicine) the research of pharmacogenetically relevant genes, and the practical implementation of the results is one of the most important elements of drug choice based on genetic variability. Within the SB project we hope to provide a background for pharmacology, drug research and drug development projects, but at the same time would like to be present with our own research field. The research of the pharmacogenomic group isn’t limited solely to enzymes and carriers associated with metabolism, but also plans on including all aspects of genetics behind drug side effects, the optimization of drug dosage. The ethnical differences behind drug effects are well-known and the optimal dosages varies according to the given population. It is well known that the Roma can be found all over the world, but their genetic profile is less known. The Roma differ from the populations where they live due to their different origin. There is considerable evidence which suggests that the Roma originate from India, thus they have a different genetic structure then the Caucasian population. Currently, the majority of research concentrates on SNP-based variations, however we can assume that in this area, more variations in relation to copy number variations with pharmacogenetic relevance are to be expected, this is also part of our future plans.

Background research of rare genetically strongly determined diseases with the help of new molecular genetic technology (next generation sequencing, array CGH). Our department plays a critical role in the research of Rare Diseases in our country. During our research we look for mutations, genotype-phenotype variants, which cause certain diseases and help us with a definite diagnosis; hopefully within the SB project more emphasis will be placed on the gene mutation-phenotype axis. Also part of the package is the research of mitochondrial DNA related diseases. These diseases are most commonly inherited metabolic diseases, which most often affect the muscular, cardiac and central nervous system. Examining the differences within the mitochondrial DNA help significantly in determining the cause of the disease.

As the coordinating department of the National Biobank Network, we have a serious Biobank collection of diseases affecting large populations. In this context diseases which appear rare, but are actually common diseases (stroke, heart attack, metabolic syndrome, etc) and show a Mendelian inheritance pattern, exhibit strong research potential: with the help of this it is possible to search for new genes, which could greatly contribute to the understanding of the disease.

Laboratories, instruments

  • ABIPRISM 3500 DNA Sequencer
  • Agilent Microarray Scanner
  • Micromass Quattro Ultima QQ massspectrometer
  • Bio-Rad Chromo4 real-time machine
  • Roche Lightcycler real-time machine

Services

  • Diagnostics
  • DNA sequencing
  • CGH array
  • Carnitine-esther profile analysis
  • mass spectrometry

R&D results

  • Richter Gedeon zRt., mass spectrometry proteomic studies, development of protein database (2009)
  • Ngene, mass spectrometry proteomic studies, protein database, conference lectures, publications
  • Bionorica (Germany), LC-MS analytical studies, publications (2008)
  • Polgár Bor Kft., LC-MS analytical and biochemical studies, conference lectures, publications
  • Bock Kft. LC-MS analytical and biochemical studies, conference lectures, publications

Research concept

The role of PARP-1 in MPK-1 expression and MAPK pathway activation in oxidative stress. Although PARP-1 is an enzyme found in the nucleus, it affects pathways originating from the cytoplasm, and mitochondria. The length of strands made up of ADP-ribose units catalyzed by PARP-1 can consist of only a few units up to 200 units, which can be disassembled quickly by poly(ADP-ribose) glycohydrolyze (PARG). ADP-ribose units are able to enter the cytoplasm and initiate mitochondrial depolarization, which induces the emission of apoptosis induction factor (AIF) as a result of oxidative stress. Studies show that nuclear PARP-1 induced ADP-riboslation and ADP-ribose units form contact with the nucleus, cytoplasm, mitochondria and cell receptors, however there is little information regarding the mechanisms behind this. During our research we inhibited PARP-1 enzyme with specific inhibitors, with the help of PARP1 siRNA technology, which resulted in the inhibition of MAP kinase. Our results proved that PARP-1 activated by free radicals regulate the activation of JNK and p38 MAP kinase. The inhibition of JNK and p38 MAP kinase was affected by the elevated levels of cytoplasmic MKP-1, which was induced byPARP-1 inhibition as a result of oxidative stress. Further results showed that as a result of the inhibition of MPK-1, the inhibition of the protective effect of PARP-1 disappeared, which shows the importance of JNK and p38MAP kinase in oxidative stress induced cell death, and furthermore the protective effect of the elevated levels of MPK-1on PARP-1 inhibition. Our results suggest that through the regulation of proteins, nuclear PARP-1 can directly affect mechanisms transmitted towards the cytoplasm.

The role of poly-ADP-ribose polymerase (PARP-1) in cardiovascular regeneration.

The activation of PI3K-Akt pathway has an important role in myocardial regeneration, earlier data shows that the inhibition of PARP enzyme activates PI3K-Akt pathway, and protects the cells from the induction of mitochondrial cell death, thus these processes play an important roles in regeneration.

As a model for chronic heart damage we used hypertensive rats, we examined the effect of PARP inhibitor compounds on heart function and regenerative processes.

Laboratories, instruments

  • HPLC, nanoLC, UHPLC, MALDI-TOF/TOF, ESI(APCI)-IT MS, ESI(Chip)-QQQ MS, NMR/µMRI
  • Cell culture laboratory
  • Fluorescence microscope
  • Flow cytometry studies
  • Proteomic studies

Services

  • Patents, protocols, collaboration research
  • Mass spectrometry and chromatography readings
  • Proteomic methods

R&D results

Research concept

The goal of this long-term program is to promote the development of non-invasive diagnostic devices for the clinical care. Clinical diagnostics has entered a new era of miniaturization. Functional micro-laboratories have been developed on a microchip platform performing a broad range of analytical assays. Special interest is focused on devices for point-of-care analysis and life science (cell analysis), with future prospects towards personalized medicine.

One of our main scientific orientations is the non-invasive search for the molecular viability markers of in vitro fertilized embryos using the culture medium. In addition to the currently used morphological embryo viability assessment new parameters are required since embryos selected for transfer using visual diagnosis does not lead to successful delivery in the expected rate. The theoretical background of the patented technology is the measurement of a quantitative protein marker allowing the selection of the morphologically fit, however, functionally non-viable embryos. Our further goal is to develop a diagnostic POCT tool for clinical purposes. Similar to that, in a non-invasive way we successfully detected embryonic DNA, chromosomal abnormalities, and the presence of the “Y” gene specific DYS14 gene in the spent culture medium.

In the case of serious systematic inflammation processes (sepsis) the use of personalized medicine is of vital importance to reliably evaluate the severity of the disease using biomarkers. Actin and gelsolin present in serum, the elevated level of orosomucoid in urine, or the quantification of serum total and free cortisol are all correlating with the severity of the patient’s condition. We also proved that the prognosis of the sepsis can be estimated by monitoring cortisol level during hospitalization.

In tumor diseases the in vitro invasivity of circulating tumor cells correlates with the severity of the disease and the metastatic potential of the tumor. The use of PoCT devices to detect and quantify circulating tumor cells helps to construct a personalized therapeutic strategy. Also the technology of 3D cell culturing is a potential model of cell-cell interactions, allowing the culturing of tumorous and healthy cells in the same matrix modeling in vivo circumstances. The technology is capable of examining the behavior and chemotherapic sensitivity of tumorous cells under circumstances similar to the human body.

Laboratories, instruments

  • Flow cytometry
  • Liquid chromatography tandem mass spectrometry (LC/MS/MS)
  • Clean-room
  • microfluidic
  • AFM (atomic force microscop)
  • Confocal microscopy

Services

  • Performing ELISA assays
  • Viability-toxicity tests on cell cultures using plate readers
  • Antioxidant capacity measurements in biological samples on plate readers
  • Detection of circulating tumor cells from peripheral blood using microfluidic chip technology
  • Western-blot analysis with quantitative chemiluminescence method
  • Quantitative HPLC measurements
  • HPLC coupled mass spectrometric analysis
  • Fluorescence spectroscopy and polarization measurements
  • DNA sequencing, PCR

R&D results

Kitti Csepregi, Andrea Valasek, Ágota Pénzes, Zsuzsanna Tóth, Éva Írisz Kiss, Ildikó Kerepesi, Balázs Horváth, István Nagy and Csaba Fekete (2012): Draft Genome Sequence of an Efficient Antibiotics Producing Industrial Strain (SZMC 14600) of Saccharomonospora azurea. J. Bacteriol. 194, No. 5, in press. IF.: 3.72.

Balázs Horváth, Judit Hunyadkürti, Andrea Vörös, Csaba Fekete, Edit Urbán, Lajos Kemény, and István Nagy (2012): Genome Sequence of Propionibacterium acnes Type II Strain ATCC 11828. J. Bacteriol. 194:202-203. IF.: 3.72.

Juhász, Á., Pénzes, Á., Peteri, Z, A., Pallos, J., P., Seffer, D., Feiszt, P., Pesti, M., Fekete, C., Vágvölgyi, C., gazdag, Z., Papp, G. (2011): Process for producing primycin, primycin conponent(s), precursors and metabolites thereof via fermentation by the use of bacterial species Saccharomonospora azurea. WO/2011/051741, 1-21. International Application No.: PCT/HU2010/000116.

Research concept

Popular views classify microbes either as a good or bad guys, however these phenomenon imply very complex processes in reality. It is no exaggeration to say that to understand host-microbe-environment interactions at the level of biological complexity is one of the greatest challenges in biology. Recently genomics, proteomics, high-throughput microarray and next-generation sequencing (NGS) technologies have extended our ability to provide new insight into the molecular basis of these fundamental questions.

As the problem of antimicrobial resistance becomes more widespread, the need for new anti-infective agents is more urgent than ever. As a part of these efforts, massively parallel NGS technologies provide a tremendous ability to typify microbes, not only on the basis of readily observable characteristics, but also upon their genetic (biosynthetic) potential.

In respect of the clinical needs, on the bases of our ongoing microbial whole genome shotgun sequencing (WGS) project, we designed strategy and workflow to isolate new microbial natural products (e.g. antimicrobials) and screening for potential producing microorganisms. It is important to highlight the fact that the lack of genome sequence information in non-model species often limits the downstream scientific activities, such as engineering microbial metabolic pathways. We hope that our structural genomics efforts will form a foundation for the subsequent research steps, like intelligent drug design, identification of new pathogenicity factors and target discovery etc.

State of art genomics approaches provides revolutionary tools with numerous applications, which can address different questions in almost all aspects of biological research. Nevertheless, one of the major challenges biologists are facing today is to understand and be able to interpret the functional complement (transcriptome, proteome) of the genome, which is a dynamic link between genotype and complex phenotype. Based on the assumption of one technology being able to standalone does not suffice for gaining a comprehensive understanding of any complex biological process. Therefore we intend to use complementary approaches i.e. transcriptomics (RNA-seq, microarray) and proteomics (2D PAGE) for developing molecular diagnostic methods to identify drug-, toxicant- and disease-related biomarkers.

Due to the broad range of microbial model systems formally used, and extensive research experience in the fields of traditional and molecular-microbiology, the Microbial Biotechnology Group is ready to face challenges in health, industry and agriculture sectors of biotechnology.

Laboratories, instruments

  • BIOSTAT Q plus new generation Fermentor-Bioreactor system
  • Next-generation and capillary sequencing platforms
  • epMotion 5070 automated pipetting system
  • FluorChem Q system for quantitative Western blot imaging
  • Two-dimensional gel electrophoresis system
  • Microfluidics-based Agilent 2100 Bioanalyzer platform for sizing, quantification and quality control of DNA, RNA, proteins
  • Ultra-fast endpoint, gradient and real-time PCR
  • Denaturing Gradient Gel Electrophoresis (DDGE) to detect single-strand conformation polymorphism (SSCP), heteroduplex analysis (HA), and protein truncation tests (PTT)

Services

Health, industrial and agricultural sectors of biotechnology. Structural- functional- and, comparative.genomics.

  • Polyphasic taxonomical characterization of microbes
  • Development of nucleic acid based diagnostic tools
  • Improvement of microbial strains and fermentation processes for the overproduction of industrial products
  • De novo whole genome shotgun sequencing
  • NGS-based transcriptome profiling

R&D results

http://aok.pte.hu/biofizika

Gabor Hild, Beata Bugyi and Miklos Nyitrai. Conformational Dynamics of Actin: Effectors and Implications for Biological Function. Invited review. 2010. Cytoskeleton, 67(10), 609-29.

Szilvia Barkó, Beáta Bugyi, Marie-France Carlier, Rita Gombos, Tamás Matusek, József Mihály and Miklós Nyitrai. Characterization of the Biochemical Properties and Biological Function of the Formin Homology Domains of Drosophila DAAM. 2010. J. Biol. Chem., 285(17),13154-69.

Research concept

The design and development of the Unit was manifested in collaboration with other related research groups in the Szentágothai Research Centre. The most important aim of the Unit is to provide modern, efficient and versatile research environment for the scientists and other corresponding investigators, so that they have excellent facilities for the engineering and preparation of biological samples of various organisation levels. Thanks to the functional multiplicity of the instrumentation available in this Unit, samples of peptides, proteins, cells and tissues can effectively be processed in the laboratory. Modern and powerful systems and applications are available for the extraction and modification, and also for the expression and purification of proteins. Fluorescent protein modifications are also possible. The conditions are provided for the use of numerous commercial preparation kits, and thus the investigation of cells and cell populations can also be manifested in this research environment. If the appropriate corresponding preliminary preparations are provided, the Unit will also provide appropriate conditions for the research with more complex biological systems, such as tissues. Based on these advances and the expected future applications the optimisation of the current set-up of the Unit is constantly in progress.
According to the current strategy the research group carries out investigations in collaboration with other groups and core facilities of the Science Building. As the optimal use of the available infrastructure assumes the application of various biophysical methods, the Bio-Imaging Center and the Spectroscopy Laboratory are considered to be the most important from these facilities.
The studies of the Biophysics Research Group are focused on the description and understanding of cellular processes essential in the function and reproduction of living cells. These processes are tightly connected to the cytoskeleton of these cells. The cytoskeleton is composed of microtubules, intermediate filaments, and actin based microfilaments. From these subsystems our research is dealing with the function and regulation of the microfilament system, and the more than 60 protein families associated to these filaments. The aim of these investigations is to characterise the molecular mechanisms underlying the function of the microfilaments, to understand the corresponding protein-protein interactions, and to describe the related changes I cell morphology.
We aim furthermore to investigate the constituents of the bacterial cytoskeleton at molecular level. Among the several types of the bacterial cytoskeleton we focus on the structure and function of the actin ortholog MreB protein. The cytoskeleton was discovered recently in prokaryotes and seems to be crucial for their survival and reproduction. Therefore, understanding the organization of this skeletal system in detail can provide essential information from an epidemiological point of view as well as can contribute to better coping with the increasing antibiotics resistance of bacteria.

Laboratories, instruments

  • Zeiss, LSM 710 laser scanning confocal micorscope,
  • Zeiss Elyra S1 structured illumination microscope, 
  • Jobin Yon Nanolog, Thermo Science DXR Raman microscope

Services

Instrumentation for the preparation of peptides, proteins, cells and tissues.

Sample preparation and approaches for fluorescence spectroscopy and microscopy invetigations
The Unit performes steady state and time resolved fluorescence spectroscopy measurements for applicants. The applied Jobin Yvon instrument is capable of fluorescence detection not only in the UV and the visible range but also in the infrared region. One can perform time resovelved fluorescence experiments with couple of hundred picosecond resolution (depends on the applied wavelength). We can provide for the external users help and assistance with their experiments, choosing their fluorophores or the experimental method for example.

Besides spectroscopic investigations the Unit provides confocal and super-resolution light microscopy approaches for the users. The Zeiss LSM 710 laser scanning confocal microscope is equipped with 6 laser lines, and can provide resolution of 200 nm. The Zeiss Elyra S1 structured illumination microscope is equipped with one laser line (488 nm) and can provide resolution around 100 nm.

The unit can provide advice for sample preparation (preparation of live and fixed cells samples, expression and purification of cytoskeleton-associated proteins), as well as for sample labeling and optimal choice of the approaches.

Instruments:

  • Jobin Yvon Nanolog
  • Zeiss LSM 710 laser scanning confocal micorscope
  • Zeiss Elyra S1 structured illumination microscope
  • Thermo Science DXR Raman microscope

Related organizations:

  • Rutherford Appleton Laboratory
  • Central Laser Facility

Contact: Dr. András Lukács, andras.lukacs@aok.pte.hu

R&D results

Research concept

The main profile of our research group is the research of viral zoonoses (diseases that are spread from animals to humans caused by viruses). Due to global warming and the expansion of human living-space, animal viruses pose a growing threat for human - and veterinary health. Pathogens causing severe epidemics are emerging more frequently thanks to global activities. One of our research aim is to identify well known and new pathogens in samples originating from Hungary and from foreign countries, thanks to our extensive international collaboration network. We intend to monitor their prevalence, characterize their genetic background and describe the mechanism of viral infection. Predominantly, we examine rodent and bat populations, but we also study mosquitoes, ticks and other arthropod vectors, too. We have established well functioning collaborations with stakeholders in public health, animal health and industry, thus we also contribute to the development of diverse diagnostic methods for the pathogens characterized in our lab.
 
Examination of pathomechanism and mechanism of action of  antivirals
On account of urbanization, people more often get into contact with infections spreading from animals to human. The spreading of diseases is almost unhindered in the population, primarily because of the emerging number of international travels. Global viral epidemics affecting whole societies do receive growing attention (Ebola, Influenza, Human infecting coronaviruses, etc.). The discovery of a new viral infection thathas the potential to cause global pandemics is setting a huge challenge for researchers and necessitates the development of new antiviral drugs. The lack of antiviral active agents can lead to the inefficient treatment of viral infections. Specific treatment is available for some viruses, but their capacity for fast mutation ensures them advantage in the competition of developing new therapeutic agents.
 
In our research we examine two effective methods differing in target points to eliminate viral infection:
  1. On the one hand, we target the replication cycle of the virus with RNA interference gene silencing. This method has been successfully applied for many viral infections. The primary goal of RNA interference is the evolutional protection against exogenous pathogens and harmful, endogenous nucleic acids. The RNA interference is generated by double-stranded RNA molecules, which can specifically attach to complement mRNA sequences, and by that leading to gene-specific translational silencing. Synthetic siRNA molecules designed by our group are evoking posttranscriptional silencing, when endonucleases degrade the target mRNAs.
  2. The other in-cell approach aims to hinder the assembly of the viral capsid with the application of specific, synthetic peptides. The interfacial attachment of low molecular weight peptides are blocking one or more “hotspots” on the surface of the given protein, thus confounds the viral capsid assembly through competitive interactions with other viral proteins.
 
Study of bat-borne viral pathogens
Bats represent a unique group of mammals due to their flying and special orientation capabilities. They are the second most diverse group among mammals with a high number of species and wide geographic distribution. They can be found in almost every continent except the Antarctica. Approximately 1600 species have been described so far, but the numbers of new species are increasing continually. Bats are highly socialized creatures, living in colonies which size can vary from small families to huge colonies with millions of specimens. They are responsible for numerous ecosystem services, for example the pollination of flowers on the tropics, pest control, and last but not least bat guano counts as a very valuable fertilizer.
Since the global SARS Coronavirus pandemic in 2002-2003, high number of viruses has been identified in bats. Some of them are able to cross species boundaries, thus able to infect other animals and human, too. Ebola viruses in Africa or Rabies virus in the Americas are good example to the risk that bats might mean. However, this risk is not limited only to the tropical regions. Lyssaviruses found in bats have been well-known in Europe for decades, but new viruses have been described recently thanks to ongoing researches. The investigation of  pathogenicity and infectious properties are the key to prevent human infection and also to protect vulnerable bat communities.
 
Besides identifying new viruses, we aim to test their pathogenicity and to estimate the risk they pose in the aspect of human and animal health care and to bat conversation.
The main directions of our research are the following:
  1. Whilst many studies are focusing on this subject in Europe, data on the situation in Central-Eastern Europe and in Hungary is rarely available. Regular monitoring of bats can give us information on the distribution of viruses in time and space. Furthermore it enables the examination of the most common genetic variants.
  2. The successfulness of virus isolation from different animal and human cell lines can give us information about their zoonotic potential.
  3. The results of virus isolation experiments from primary cell lines and immortalized cell lines are highly important, because it enables us to establish an applied laboratory model and it also gives an opportunity to study the chiroptera-borne viruses virus-host interactions. These data could give an essential insight to further investigate pathomechanisms and lay ground for clinical studies.
 
Hantaviruses research
Hantaviruses are primarily borne by rodents ( rats, mice, voles), shrews and by bats, according to the most recent studies. The virus does not sicken animals, but infected animals excrete the potentially infectious pathogen for their whole life span. The virus can enter the human body by inhaling dust contaminated with dry urine from infected animal. Many type of Hantaviruses found in Hungary can cause severe, sometimes life-threatening infections. The most common manifestation is the hemorrhagic fever with renal syndrome, which causes severe kidney and liver malignancies. Most of the patients require hospitalization due to emerging renal failure. The viruses is spread by rodents living in the woods, but due to human expansion the living habitat of these rodents are intersecting human living space. Hantaviruses mean cumulative burden for public health. Mostly people doing fieldwork in agriculture and forestry are affected, but soldiers, trail runners and hikers are also jeopardized.
 
Our research group aim to assess the presence of viruses in animals known to spread Hantaviruses. Furthermore, we aim to genetically characterize these pathogens, examine the dynamics of infection between specimens and areas. Finally, in collaboration with the clinics of the University of Pécs, investigation of patient cases that require hospitalisation, monitor the course of the disease and develop the diagnostics of hantaviruses is also comprised in our activity.
 
Ecology and epizootiology of zoonoses
Drastic acceleration of globalization and urbanization resulted in the change of natural habitat globally, that led to the alteration of ecological systems and the structure of animal communities. Cohabitation between animals and human became more close, the contact events are increasing rapidly.
The above mentioned processes affect the prevalency of animal-borne infectious diseases (zoonoses) both directly and indirectly, as the risk of human infection is emerging. The risk of diseases is relevant on all continents, most commonly among rodents living in cities (Rodentia), different thick species (Ixodidae), mosquitos (Culicidae), horse-flies (Ceratopogonidae). Although studies on zoonoses are multifaceted, the ecological aspects of spreading pathogens (seasonality, distribution, sensibility, impact of collateral occurrence, risk of urbanization) are not well-described. For this reason, our research group has set a new, interdisciplinary direction, called “Diseases Ecology”. We intend to investigate the ecological relevance and background of infectious diseases, beside detecting zoonoses in urban areas (viruses, bacteria, protozoon and vermins). Thus we intend to collectively study vector and host organisms, their distribution in time and space, and the affecting environmental circumstances.
In our research we apply the methodology of different fields, such as Microbiology, Molecular Biology, Epidemiology and Ecology.  Laboratory work is well complemented with the investigation and modelling of ecological influencing factors with complex statistical analysis.
 
Research of insect-specific  flaviviruses
Several single-stranded RNA viruses belong to the Flaviviridae genus that is highly significant in public health, for example Dengue-virus, Yellow fever virus or West-Nile virus. However, flaviviruses are arthropod-borne, it can spread between vertebrates and arthropod vectors by horizontal transmission. Some of the flaviviruses are also transmitted horizontally and infect vertebrates, but their vector is unknown. A new, small group of flaviviruses has been discovered in the last decade, namely the group of insect-specific flaviviruses. After their discovery, it has been observed that insect specific flaviviruses can only replicate in mosquito hosts, and they lack the capability to replicate in vertebrate hosts. Beside this, they are globally widespread, and their subsistence is ensured by vertical transmission.
In contrast with other group of flaviviruses, the role of insect-specific flaviviruses in nature are not well known, although many in vitro studies focus on the investigation of this problem. It is likely that insect-specific flaviviruses are able to suppress the reproduction of human pathogen flaviviruses. Even though, according to recent studies insect specific flaviviruses are not capable to cause human disease, this matter need to be further investigated in order to certify that they are not able to develop into human pathogenic viruses. Answering this question, could also give us a broader picture on why certain flaviviruses can become considerable human pathogenic viruses, whereas others can not replicate in vertebrates.

Laboratories, instruments

Services

R&D results

  • Water management optimization of the headquarter of Pannon Power Zrt.
  • Qualifying analysis of the air technology ventilation elements of the Pécs Conference Centre
  • PTE Science Building 7000 m2 international research centre energy design
  • Positive energy production and office unit for RATI Ltd. at Sikonda, creation of its climate concept.

Research concept

Smart City Energy – Energy design

Dr. Bálint Bachmann, associate professor
Dr. István Kistelegdi Jr., associate professor
Dr. András Reith, assistant professor
Mihály Baumann, assistant professor

Joining the EU Smart cities and communities initiative, we would like to focus our research on identifying the technological solutions needed for middle sized cities of EU’s convergence regions to efficiently reach EU climate change and carbon reduction targets. The main focus of our research:

  • Low energy consumption building, energy efficiency through refurbishing.
  • Efficiency development of city energy grids

Smart City ICT – Info-Communication Technology

Dr. Péter Iványi, associate professor
Dr. Barry Topping, professor
Dr. Frederick Magoules, professor
Dr. Géza Várady, associate professor

  • We are seeking ICT solutions for our smart city energy efficiency initiatives. Fields of research: intelligent building management, intelligent utility networks, traffic management and planning.
  • Low carbon public transport and sustainable mobility

Smart City LCA – Life-Cycle Assessment

Dr. Anita Dolgosné Kovács, associate professor
Dr. Csaba Leitol, PhD Student, researcher
Csaba Vér, PhD Student, researcher

  • Product LCA (ISO 14040-44, product footprint)
  • Process LCA (waste management option analysis, organization footprint)

Smart City EBA – Resource efficient adaptation

Dr. Tibor Kiss, senior researcher
Dr. Ágnes Lindenbach, professor
Ernő Dittrich, assistant professor
Dr. László Bajnai, assistant professor

Our research field is to enhance adaptation to climate change, and test local application of global models through integrating green infrastructure management practices into city development (water management, green space management, flood protection), climate model simulation in supercomputer environment, comparing results with empirical data.

Laboratories, instruments

  • AAS, ICP-OES, portable gas chromatograph, water quality analyzing and measuring system, measuring equipment for analysing the emission of diffuse air pollution sources, digital sieve shaker machine, emission measuring laboratory, gas analysers (SO2-CO-NOx-O3), noise technology laboratory
  • RELUX, Solar computer, Shell solar path, Meteonorm, Ecotecht, Wis, 3D studiomax, Archicad

Services

Construction, energy, ICT, utility services, sustainable production

  • Efficient city maintenance services
  • Development of ICT solutions for city management
  • LCA evaluation systems for production and organizations
  • Energy and climate concept development, complex planning and construction supervision for private and public zero and positive energy housing

R&D results

Patents

  • 2009. Pulmonary tissue model – Hungarian patent (No.: P0900278) International patent pending (PCT/IB2010/051978)
  • 2010. Pulmonary adenocarcinoma model – patent pending

Research concept

Our research group focuses on the involvement of Wnt signaling in the ageing process of the lungs and the thymus. Wnt signaling plays a pivotal role in physiological aging as well as in age-associated diseases including cancer formation and inflammation.

Laboratories, instruments

Laboratories

  • molecular biology laboratory
  • tissue culture laboratory suitable for murine or human tissue processing

Instruments

  • Biobot 3D bioprinter
  • Nanostring high content screening platform
  • 3D high accuracy qPCR platform
  • LAS4000 laser protein analyser
  • Nanodrop / Qubit spectrophotometers

Services

Our research group is specialized on providing services in the field of biotechnology and pharmaceutical research. The applied methodology includes: 3D bioprinting for educational and research purposes, recombinant viruses, transgenic cells and tissues, gene cloning and modification, inducible vectors, complex tissue models (lung, thymus, liver etc).

R&D results

Research concept

Laboratories, instruments

Services

R&D results

  • examination of urinary steroid profiles: Hungarian clinics and hospitals (Pécs, Szombathely, Kaposvár, Veszprém, Debrecen, Budapest)
  • statistical data evaluation: several clinics at the University of Pécs
  • qualitative and quantitative analyses of pharmaceutical samples: PannonPharma Ltd., University of Pécs, Dep. of Laboratory Medicine
  • Public Limited Company for Radioactive Waste Management (PURAM), MECSEKÉRC Environmental Protection Public Limited Company

Research concept

  • Liquid chromatography, gas chromatography, capillary and microchip electrophoresis, mass spectrometry, sample preparation
  • Study of environmental contaminants and microorganisms interactions. Biosorption and biodegradation. Bioanalysis
  • Geomicrobiology and Biogeochemistry
  • Environmental Geology, Sedimentology
  • Sedimentary petrography
  • Permo-Mesozoic and Pliocene-Quaternary stratigraphy
  • Tectonics and morphotectonics of South Transdanubia

Laboratories, instruments

  • Agilent 1290 UHPLC – Agilent 6530 Q-TOF MS: liquid chromatograph and mass spectrometer
  • Agilent 1100 liquid chromatograph: autosampler, thermostat, diode array and refractive index detector
  • Agilent LC/MSD Trap XCT Plus mass spectrometer
  • Shimadzu Prominence liquid chromatograph: degasser, autosampler, binary pump, diode array detector
  • Agilent 6890N gas chromatograph, 5975 mass spectrometer detector, 7683 injector and autosampler
  • Biofocus 3000 capillary electrophoresis system, Agilent 3D capillary electrophoresis system, Agilent 2100 Bioanalyser, Kapillarelectrophorese ZKI 02-A (ITP instrument), Unicam CE - Picometrics LIF capillary electrophoresis system
  • Perkin-Elmer 2380 Atomic Absorption Spectrophotometer
  • Thermo Scientific Genesys 10S double beam UV/Vis spectrophotometer
  • Malvern Mastersizer 2000 – particle size analyzer
  • Malvern Zetasizer Nano Z – Zeta potential measurement in aqueous and non-aqueous dispersions
  • photoreactor
  • Nikon Eclipse polarizing microscope
  • Malvern Mastersizer 3000 - particle size analyzer
  • X-ray powder diffractometer (XRD)

Services

Pharmaceutical, health, food, environmental, and chemical industry, mining and natural resources

  • Method development for the qualitative and quantitative analyses of biological, environmental, and pharmaceutical samples by high performance liquid chromatography, gas chromatography, capillary and microchip electrophoresis and LC-MS, GC-MS, CE-MS methods.
  • Determination of urinary steroid profiles for medical diagnostic purposes from 24-hours urine of outpatient or inpatient.
  • Development of novel, environmental-friendly biosorbents, biocomposites for environmetal technology. Development of a novel environmental technology based on biosorption and biodegradation. Analysis and assorting of organic contant of wastewater and contaminated surface water. Biodegradation and photocatalytic degradation of organic contaminants in water and soil. Completion of expert opinion, expert’s report, experimental analysis.
  • Analysis of the surface properties of biosorbents
  • Practice in environmental geology, expert report
  • Physical charctheristics of sediments and soils
  • Phase analysis of solids (bulk + clay minerals)

R&D results

  • 210 publications (in international journals, cumulative impact ca. 460); 1900 independent citations
  • 9 basic patents in pharmaceutical and pesticide chemistry (announced in more than 30 countries).
  • 25 years cooperation with Gedeon Richter Pharmaceutical Works Ltd. (steroid chemistry group). Synthesis of novel, diphenyl ether-based pesticides (Budapest Chemical Works). Investigation of the copigmentation in red wines (Vylyan Viticulture).

Research concept

Preliminaries

The dendrimers are one of the most important nanosize building blocks. Their technological and practical applications are also remarkable. Beside the industrial use of the dendrimers gain wide application also in pharmacology. The efforts aiming at the development of dendrimers, among them our present research, are focused on the synthesis of those ones able to form inclusion derivatives with the target compunds.

The first poly(amido)amidoamine (’PAMAM’) dendrimers were followed by more complicated structures containing further heteroatoms, cross-linkings and graphite-like substructures.

Our target compounds are the so-called host dendrimers which may gain application both in pharmacology and analytical chemistry.

The topics to be investigated

  • One of our goals is the synthesis of dendrimers containing either novel trisubstituted core or tetravinyl/tetraallylsilanes. Homogeneous catalysts of high chemo- and regioselectivities will be used. The preparation of higher generation dendrimers will be carried out by divergent methodologies, i.e., methodologies starting from the core unit.
  • The homogeneous catalysts will be exploited in the synthesis of amide-functionalised dendrimers, i.e., the synthesis of conventional structures will be carried out by novel reactions of high selectivity. On the other side, transition metal catalysed cross-coupling reactions will be used for the synthesis of novel dendritic structures.
  • Our basic compounds, serving as core derivatives, are 1,3,5-triiodobenzene, 2,4,6-triiodoaniline and silanes containing alkene functionalities. The iodoarene-type substrates and the silane derivatives are promising substrates in high-yielding carbonylation, coupling and hydroformylation reactions, respectively.

Laboratories, instruments

  • Laboratory devices necessary to carry out synthesis of dendrimers (inert Schlenk-technique, high-pressure autoclaves)
  • Analytical methods (400 MHz NMR, FT-IR-Raman, MS, fluorimetric methods)

Services

Chemical industry, pharmaceutical industry

  • Development of carbonylation catalysts of high selectivity.
  • Synthesis of iodo-containing and silane substrates able to form dendritic cores.
  • Structural determination of first- (second-, third-) generation dendrimers.
  • Investigation of the practical application of dendrimers.

R&D results

  • THz beam source based on optical rectification – Hungarian announcement nr.: P1000514; International announcement nr. : PCT/HU2011/000081
  • Optical device for broadband nonlinear optical processes – Hungarian announcement nr.: P1000179; International announcement nr. : PCT/HU2011/000031
  • Set-up and method for manipulation of electrically charged particles – Hungarian announcement nr.: 107592-13373d
  • Method and device for generation of high voltage and large current fast electric pulses in plasma channel – Hungarian announcement nr.: P1000368; International announcement nr. : PCT/HU2011/000069
  • Undulator with short period – Hungarian announcement nr.: P1100452

Research concept

Generation and application of terahertz (THz) pulses with high pulse energy, and with extremely high electric field strength that is sufficient for nonlinear THz spectroscopy applications. Searching for new application possibilities in the fields of material-, medical-, and life sciences.

Manipulation, acceleration, focusing and temporal shaping of electrically charged particle bunches (electrons, protons, ions) with THz pulses having extremely large electric field strength. Elaboration of the theory of a possible table-top proton accelerator making possible the use of protons having low energy for hadron therapy applications. Generation of single cycle UV and X-ray radiation with Thomson scattering.

In the frame of ELI (Extreme Light Infrastructure) generation of attosecond light pulses with the method of THz assisted high harmonic generation.

Our results as far as here: Presentation of optimal parameters for design of tilted pulse-front based THz generator scheme. It was shown that in case of using longer wavelength than the typical 800 nm in a tilted pulse-front excitation scheme semiconductors (like ZnTe, GaP) are competitive with LiNbO3 from the point of view of efficiency. It was shown, that in case of LiNbO3 the peak THz electric field strength can be increased by more than one order of magnitude using ~500 fs pump pulse length, and cryogenic temperature. With this technique it is possible to generate single cycle THz pulses with pulse energy exceeding 10 mJ, and with peak electric field strength of 100 MV/cm with central frequency about 1 THz.

Laboratories, instruments

  • Clean room environment and controllable temperature conditions is available, where a THz source with milliwatt average power operates presently.
  • Time Domain THz spectrometer with 3 THz bandwidth. Near infrared pulsed lasers, with characterized beam parameters.
  • Optical equipments and diagnostic instrumentation from the visible to the far infrared frequency range.

Services

Scientific research, semiconductor industry, medicine industry, security-technique

  • Time Domain terahertz Spectroscopy (TDTS)
  • THz pump – probe measurements

 

Nagy intenzitású, különleges hullámhosszú ultrarövid impulzusú lézerek - Külső felhasználók részére szolgáló felhasználási szabályzat nyilvános elérhetősége

Application Form

R&D results

Research concept

Spectrofluorimetry characterization of fluorescent materials useful in several fields of biology and biomedicine. Developing of nanoprobes of high stability and high fluorescence intensity.

Study of: (1) Cavitands; (2) Luminescent quantum dots; (3) Single-wall carbon nanotubes (SWCN); (4)

Lanthanide complexes capable of two-photon NIR-to-VIS conversion.

Intra- and intermolecular energy transfer in lanthanide complexes.

Nano- and picosecond study of protein dynamics.

Dielectric relaxation of small fluorophores in the time range of femto- and picoseconds.

Numerical spectral analysis and data mining in complex samples

Time-resolved and steady-state fluorescence spectroscopy analysis of different liquid and solid samples.

Developing of integrating spheres for determination of real spectra and exact concentration of scattering and/or low concentration solutions.

Laboratories, instruments

  • Jobin-Yvon Nanolog spectrofluorometer. Spectral range: 200-1600 nm (UV-VIS-NIR), Time range: 50 ps – 100 ns;
  • Jobin-Yvon Fluorolog Tau3 spectrofluorometer. Spectral range: 200-1000 nm. Time range: 0,1 ns – 100 ns;
  • Perkin-Elmer LS50B luminescence spectrometer for steady-state and phosphorescence studies;
  • Spectrophotometers for absorption and transmission measurements.

Services

Engineering Sciences, Natural Sciences

  • Determination of real spectra and exact concentration of scattering and/or low concentration solutions.
  • Spectral measurements for material studies, light source checking etc. In the 200 – 1600 nm spectral range. Measurements of excitation, emission, synchronous excitation spectra and decay curves. Vary fast analysis of complex samples using Matrix Isopotential Synchronous Fluorimetry (MISF).
  • Optical planning of indoor and outdoor displays of very high contrast and good visibility for environment of high luminosity using LED sources.

R&D results

IBL rat monoclonal antibody series

Developmental Biology of Peripheral Lymphoid Organs

Research concept

Laboratories, instruments

  • Tissue culture laboratory
  • immunoserology equipment
  • multiparameter flow cytometry
  • fluorescence microscopy

Services

Biotechnology

  • Production and characterization of monoclonal antibodies in cellular and molecular immune assays
  • Phenotypic analysis of human and mouse lymphoid cells, establishment and characterization of chimeric and transgenic animals.

R&D results

Research concept

Laboratories, instruments

Services

R&D results

Research concept

Laboratories, instruments

Services

R&D results

Kooperációk külső intézetekkel:

dr. Gábriel Róber, PTE TTK, Biológiai Intézet, Kísérletes Állattani és Neurobiológiai Tanszék, ill. SZKK, Neurobiológia Kutatócsoport: Különféle rágcsáló fajokból származó, és alkalmanként humán retina funkcionális morfológiai, immunfluoreszcens vizsgálata lézer pásztázó, konfokális mikroszkópiával

dr. Atlasz Tamás, PTE TTK, Sportbiológia Tanszék, Testnevelés- és Sporttudományi Intézet, ill. SZKK, Neurobiológia Kutatócsoport: Urokortin jelátviteli hatásának vizsgálata patkány feokromocitóma (PC12) sejtekben

dr. Tóth Márton, PTE ÁOK, Neurológiai Klinika: Antiepileptikumok jelátvitelre kifejtett hatásának vizsgálata humán cortexben (jelenleg a mintagyűjtés fázisában)

dr. Ács Péter PTE ÁOK, Neurológiai Klinika: Cuprizone lehetséges idegrendszeri terápiás hatásainak vizsgálata modell rendszerekben.

Research concept

Onkolítikus virus indukált génexpressziós változások

Az onkolítikus vírusok szelektív citotoxicitást mutatnak tumorsejtekkel szemben, így a daganatok elleni küzdelem ígéretes eszközei. Egyik részletesen tanulmányozott típusuk a madarakban patogén, de emberre ártalmatlan Newcastle betegség vírusa (NBV). Kutatócsoportunk egy attenuált NBV-törzs (MTH-68/H) citotoxikus hatásának mechanizmusát tanulmányozza. Az MTH-68/H minden általunk vizsgált humán és rágcsáló tumor sejtvonalra citotoxikus hatású, míg normális fibroblasztok rezisztensek a vírussal szemben. PC12 patkány phaeochromocytoma sejteket használva modellrendszerként megállapítottuk, hogy az MTH-68/H (I) replikálódik ezekben a sejtekben, ezáltal (II) apoptotikus pusztulásukat okozza; (III) a vírusindukált sejthalál nem igényli a p53 fehérje részvételét; (IV) a folyamat során a stresszkináz utak (JNK és p38 MAPK) elnyújtott aktivációja figyelhető meg; (V) a vírus-indukált sejthalálban az endoplazmatikus retikulum stressz valószínűleg fontos szerepet játszik. Mivel a vizsgált tumor-sejtvonalak MTH-68/H-érzékenysége nagyon különböző, az onkolítikus vírus-terápia hatékonyságának „megjósolásához” fontos lenne azonosítani azokat a jelátviteli fehérjéket, melyek meghatározzák a tumorsejtek NBV-érzékenységét. Erre a célra PC12 sejtek mutagenizálásával olyan szubklónokat izoláltunk, melyek teljes rezisztenciát mutatnak MTH-68/H vírussal szemben. Ezekben az NBV-rezisztens sejtvonalakban vizsgáljuk a vírus-fertőzés különböző fázisait (vírus-adszorpció és –internalizáció, a MAPK-utak aktiválása, interferon-szekréció, endoplazmatikus retikulum stressz, apoptózis). Az NBV-érzékenységet meghatározó fehérjék azonosítását megkönnyíti az NBV-fertőzött PC12 sejtekben elvégzett génexpressziós profil vizsgálat. A fertőzést követően többszáz gén indukálódott, míg sok más gén expressziója csökkent. Ezek jelentőségének vizsgálata folyamatban van.

 

2. A differenciáció jelátvitelének tanulmányozása

Munkacsoportunkkal mitogén-aktivált protein kináz kaszkádok enzimeinek aktivációját és lokalizációját vizsgáljuk idegsejt prekurzor (patkány feokromocitóma / PC12) tenyészetekben, hagyományos (idegi növekedési faktor / NGF-fel) kiváltott, illetve alternatív (pl. proteaszóma gátló, vagy urokortin) kezelést követő stimuláció / differenciáció során. Vad típusú és mutáns sejtvonalak segítségével keressük az egyes szerek által kiváltott differenciációhoz szükséges, illetve elégséges enzim aktivációs és sejten belüli eloszlási mintázatokat. Alkalmazott módszereink közt meghatározó a Western-immunoblot, immunprecipitáció és konfokális lézer pásztázó fluoreszcencia mikroszkópia.

 

3. Endoplazmatikus stressz vizsgálata glioblastoma multiforme sejtekben

A glioblastoma multiforme (GBM) a központi idegrendszer leggyakoribb agydaganata, igen agresszív növekedése miatt klinikai prognózisa rossz. A GBM genetikai háttere meglehetősen heterogén a tumor képződésben szerepet játszó számos jelátviteli út miatt, ami jelentősen megnehezíti általános kezelések alkalmazását gyógyításában. Az ubikviter módon expresszálódó endoplazmatikus retikulum (ER) stressz indukálta GRP78/BiP fehérje gátlása potenciális célpontként szolgálhat a glioblastoma kezelésében, mivel ez a fehérje az esetek nagy részében overexpresszálódik és ezzel hozzájárul a tumorsejtek fokozott túléléséhez, a metasztázis kialakulásához, az angiogenezishez és a drog rezisztencia kialakulásához. Célkitűzésünk, hogy a GRP78/BiP fehérje shRNS-el történő gátlásának hatását vizsgáljuk az ER stresszt indukáló tunikamicin és a hagyományos kemoterápiában alkalmazott temozolomiddal kombinációban. Kísérleteinkhez különböző glioblastoma sejtvonalakat és primer tumor sejtkultúrákat használunk fel, amelyeket monolayerként, egy síkban vagy többsejtes tumor szferoidként fogunk tenyészteni. Meghatározzuk és összehasonlítjuk a kombinációs kezelések hatásait a sejtek proliferációjára és túlélésére, génexpressziós profiljára, különböző jelátviteli utak aktivitására és a drog érzékenységre. Ezen kívül, miRNS-eket izolálunk a primer sejtkultúrákból és a betegek vér exoszómáiból és megpróbálunk korrelációt találni a kezelés kimenetele és a GBM betegek miRNS profilja között. A kutatás várható eredményei lehetőséget nyújtanak egy új terápiás stratégia kidolgozására és prognosztikus biomarkerek felderítésére ebben a meglehetősen rosszindulatú és gyógyíthatatlan betegségben.

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  • Konfokális lézer pásztázó fluoreszcencia mikroszkóp

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