Recent advances in bioanalytical techniques especially in modern mass spectrometry (MS) have made the possibility to obtain sequence information from subpicomolar quantities of fragmented ancient proteins and peptides. Our goal is to extract and identify certain peptides or proteins from human archeological skeletal remains which can be used as possible paleopathological biomarkers. The identification of the biomarkers would be performed by matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI TOF/TOF MS).
Co-supervisor: KÁLMÁN, Nikoletta
Sepsis is one of the leading causes of death in intensive care units affecting more than 18 million people worldwide. Although precise mechanisms by which sepsis leads to multiple organ dysfunction are unknown, growing evidence suggests that blocking the main inflammatory signaling pathways might be a strategy to control the pathophysiology of sepsis. Nuclear factor-κB (NF-κB) as one of the most important inflammatory transcription factors plays a crucial role in regulation of uncontrollable inflammatory processes leading to sepsis. Naturally abundant biomolecules with significant anti-inflammatory effect (e.g. polyphenols) are in the limelight of our studies. We focus on the effect of these biomolecules on enzymes and adaptor proteins in signaling pathway between the cell surface TLR4 receptor and the NF-κB transcription factor.
Monocrotaline induced pulmonary hypertension is one of the most accepted animal model for WHO I pulmonary hypertension. Beside the effect on lungs other organs are damaged as well. Kidney failure could be detected after monocrotaline injection in rats. Treatment with PARP inhibitors can reduce the injury. We detect morphological as well as biochemical changes.
Lipids form a very heterogeneous group that play an important role in the human body. They are important not only in building up membranes and as energy storage, but intensive research in recent years has highlighted the fact that they also play a key role in various signalling processes. During pregnancy, from fertilization to childbirth, very rapid and intense changes take place in the body of both the mother and the fetus, which of course also affect lipids. To better understand the biochemical background of both physiological and pathological processes, it is essential to monitor changes in lipids during pregnancy.
Supervisor: TAKÁTSY, Anikó
Co-supervisor: Dr. AVAR, Péter Ágoston
Drug residues and personal care products enter the environment and influence natural ecosystems. To monitor and to overcome this problem the compounds should be identified and quantitatively analyzed. Samples from natural waters, fish and snail tissues are extracted and analyzed for e.g. estrogenic compounds and their degradation products originated from e.g. contraceptives, to describe the biochemical changes, caused by them.
Sepsis is one of the leading causes of death in intensive care units affecting more than 18 million people worldwide. Although precise mechanisms by which sepsis leads to multiple organ dysfunction are unknown, growing evidence suggests that blocking the main inflammatory signaling pathways might be a strategy to control the pathophysiology of sepsis. Nuclear factor-κB (NF-κB) as one of the most important inflammatory transcription factors plays a crucial role in regulation of uncontrollable inflammatory processes leading to sepsis. A number of enzymes and adaptor proteins play important role in signaling pathway between the cell surface TLR4 receptor and the NF-κB transcription factor, localized in the nucleus, thereby our studies focusing on these molecules.
Supervisor: TAKÁTSY, Anikó
Co-supervisor: Dr. AVAR, Péter Ágoston
The stress, e.g. oxidative stress influences the cell fate, induces aging and can lead to apoptosis or necrosis. The metabolic changes provide complex information and new perspectives to describe these processes. The quantitative analysis of the metabolites (e.g. small acidic molecules, nucleosides? ) leads to a better understanding of biochemical changes.
Supervisor: TAKÁTSY, Anikó
The oxidative stress that induces degradative processes in the cells and can lead to apoptosis or necrosis can be decreased with the help of antioxidants. It is known already that polyphenols, like malvidin or resveratrol, stilbenes and phytoestrogens are antioxidants and have a protective role. The quantitative analysis of these molecules and the comprehensive tests can bring us closer to a better understanding of the processes and it can be used in a better medication as well.
Supervisor: NAGYNÉ, Kiss Gyöngyi
White adipose tissue is an endocrine organ producing several hormones (e.g leptin, adiponectin, resistin etc.) and cytokines (e.g TNF-α, MCP-1, IL-6 etc.) involved in the regulation of tissue insulin sensitivity. Obesity-associated decrease in tissue insulin sensitivity, also called insulin resistance, is a major risk factor for type 2 diabetes and cardiovascular diseases.
Lysophosphatidic acid (LPA) is a phospholipid mediator that regulates several physiological responses ranging from cell proliferation and differentiation to cell migration and survival, via specific cell membrane and nuclear receptors. Recent studies showed that white adipose tissue secretes a significant amount of LPA and also the key enzyme of LPA production, autotaxin. The expression of ATX is increased in the adipose tissue of obese insulin-resistant individuals and mice. Furthermore, it has been shown that LPA decreased pancreatic insulin secretion and glucose tolerance. By using isolated mouse adipocytes and LPA receptor knockout mice models we aim to investigate the effect of LPA on the production of certain hormones (leptin, adiponectin, resistin) and cytokines (TNF-α, MCP-1, IL-6) involved in the regulation of tissue insulin sensitivity, and also the LPA receptors and intracellular signaling pathways involved in this process.
Regulatory pathways involved in cardiac development may have utility in reprogramming cardiomycytes to aid in cardiac repair. As an alternative to stem cell therapy we hypothesize that small, secreted peptides or their derivatives together with other small molecules such as microRNAs are alternatives for tissue repair stimulation. These molecules are believed to modulate the activation of resident cardiac stem/progenitor cell populations. A systematic approach to understanding the signaling mechanisms actuated by such proteins will benefit the design of novel therapeutic agents to promote cardiac repair and regeneration in adults and children.
Co-supervisor: Dr. DEBRECENI, Balázs
A high variety of causes lead to cell death, however, a surprisingly moderate number of mechanisms are involved in the process itself. Central role of the mitochondrion in governing cell survival and death is well established, still the mechanisms affecting the integrity of the
mitochondria are elusive (http://www.nature.com/cdd/journal/v7/n1/full/4400645a.html). This project is aiming at identifying and elucidating the regulatory pathways of such mechanisms.
Curcumin is a hot topic in contemporary research, as it shows very interesting biological effects regarding its tumor disease related activities, beside being a well known antioxidant and radical scavenger. Carotenoids, on the other hand, are a traditional research focus in the Research Group for Carotenoids with long tradition at our university. The covalent coupling of the two mentioned molecular moieties might lead to the enhancement in the antioxidant effects and possible further advantageous synergistic interactions widening the spectra of the individual biological properties. To be able to examine this proposed combination, the organic synthesis of the conjugates is underway and provides the prospective student an insight into the organic synthesis methods in theory and in practice.
The antioxidant activity and bioavailability of hydrophilic carotenoids surpasses those of the natural parent carotenoids. As only a few such compounds are known in Nature our goal is the synthesis and pharmacological study of this kind of derivatives. Furthermore, dendrimers -already of nano size- built up from such carotenoid derivatives maybe of interest.
Supervisor: NAGY, Veronika
Carotenoids are natural antioxidants and their biological activity can be enhanced by chemical modifications. So-called kappa-carotenoids, which are mainly responsible for the red colour of paprika species, are among the best antioxidants, however, their synthetic modifications have not been studied yet. We focus on the covalent coupling of carbohydrates, fullerenes, or antibiotics to carotenoids with kappa-end group, and other naturally occuring carotenoids. The synthesized products will be studied as antioxidants in vitro and in vivo.
Co-supervisor: Dr. VERES, Balázs
A redox imbalance characterizes the pathomechanisms of various diseases. Here, we aim to assess the importance of emerging oxidative stress in the liver tissue during microbial infection. For this purpose, we use new generation sequencing (NGS) data originating from bacterial lipopolysaccharide (LPS) exposed wild type, Cyclophylin D knock-out -a key regulator of the mitochondrial permeability transition pore- and an antioxidant compound, TEMPOL pre-treated mice model. The primary focus is laid on the network-based modelling and analysis of LPS-induced gene expression alterations, and hypotheses testing on the role of oxidative stress in sepsis-related tissue damage and organ dysfunction.