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Student Researchers' Society Topics

Co-supervisor: Dr. ZSIDÓ, Balázs Zoltán

GFR is an essential clinical parameter describing kidney function. The present topic involves a comparative literature survey of the methods of determination of GFR as creatinine clearance. In case we can find available literature and electronic healthcare records, we will apply statistical approaches to evaluate the significance of the state of art methods and will propose probable changes. Likewise, depending on the availability of data we will investigate the connection between physiological parameters (such as blood pressure) and GFR.

Co-supervisor: Dr. BÖRZSEI, Rita Judit

Computational docking is an essential tool of drug design widely used by pharmaceutical companies. The project will focus on the prediction of structure and energy of drug-target interactions by computational docking. Both capabilities and limitations of the method will be investigated on a set of drug-target systems. The set will be assembled on the basis of common interest of the student and the supervisor.

Co-supervisor: Dr. BÖRZSEI, Rita Judit

Application of pharmacoinformatics tools is essential in modern drug design. The project will focus on the development of computational tools facilitating efficient discovery of potent drug candidates. The tools work with atomic resolution structures of (protein) targets and calculate the strength of drug-target interactions. Students interested in physical chemistry with programming and/or scripting skills (interest) are good candidates for participating in this project.

Co-supervisor: Dr. GASZNERNÉ, Kormos Viktória

Clinical and experimental data indicates that chronic stress increases pain sensitivity, but the underlying mechanisms are largely unknown. The pain perception of mice exposed to chronic restraint stress is assessed with functional tests in our experiments. Neuronal activation caused by stress and pain is examined with immunohistochemistry both in the central and peripheral nervous system. The role of peripheral capsaicin-sensitive sensory neurones is explored with desensitized animals. Investigation of the stress-induced hyperalgesia may contribute to the understanding of stress-related pain syndromes (e.g.: fibromyalgia) and to the identification of new drug targets.

Co-supervisor: Dr. ZSIDÓ, Balázs Zoltán

Attacking the assembly of HIV capsid is promising strategy of fighting AIDS. Proteins of the viral capsid are good targets of drug design due to their low mutation rates. In the project, available assembly inhibitors will be collected and their mechanisms will be investigated by computational techniques. Based on the collected information and the uncovered mechanisms, new inhibitors will be also designed.

Co-supervisor: ACZÉL, Timea

Orofacial pain and primary headache disorders are among the most debilitating pain conditions. Due to several therapy-resistant patients, the therapy of migraine is far from being optimal, and it is still an unmet medical need. Therefore, understanding the pathophysiological mechanisms is crucial to identify key mediators and determine novel therapeutical targets. Thus, we investigate the role of different potential target molecules in pain models using pharmacological tools (agonists, antagonists) and gene-deficient mice. Tissue samples from our experiments are analyzed by qPCR for gene expression and immunohistochemistry for protein level analysis.

Co-supervisor: Dr. POZSGAI, Gábor

The treatment of the chronic inflammatory diseases, like allergic dermatitis and inflammatory bowel diseases (IBD) means still a problem of modern medicine. In the progression of these diseases neurogenic factors play an important role. Neuropeptides released from the capsaicin-sensitive sensory neurons, as well as inflammatory and immune cells influence the inflammatory processes, but their complex roles have not been cleared in precise details. Some of these peptides exert proinflammatory (SP, NKA, CGRP), while others exert antiinflammatory effects (opioid peptides, somatostatin, cortistatin, PACAP). Beside the classical peptide mediators of neural origin, hemokinin-1 and endokinins, expressed mainly in inflammatory and immune cells, were discovered a few years ago. All these peptide mediators are released on response to endogenous or exogenous stimuli, through the activation of Transient Receptor Potential Vanilloid 1 (TRPV1) and Ankyrin 1 (TRPA1), or independently of that. Antagonising the effect of the proinflammatory peptides, as well as the precise identification of the mechanisms of antiinflammatory mediators may enable the development of antiinflammatory drugs acting on new target structures. Therefore, our experiments aim to investigate the interactions between the neurogenic components and the immune system in animal models of dermatitis and IBD, with the help of functional, morphological, immunological, molecular biological, as well as in vivo imaging techniques.
Key words: neuro-immune interaction, neuropeptides, skin, dermatitis, bowel, IBD, proinflammatory, antiinflammatory

Co-supervisor: Dr. BÁTAI, István Zoárd

In this topic effects of hydrogen sulfide, sodium polysulfide and dimethyl trisulfide are investigated. Beside classical models of nociception and inflammation, animal modles of neuropathic pain, arthritis and pancreatitis are utilized. Mechanical and heat sensitivity, myeloperoxidase enzyme activity, oedema formation, rate of plasma extravasation as well as activation of corresponding parts of the CNS by immunohistochemistry are detected during the experiments. 
 

Co-supervisor: Dr. HORVÁTH, Ádám István

Amino-oxidases neutralise the pharmacological effects of exogenous and endogenous biogen amines. However, their reaction products (aldehyde, hydrogen-peroxide, ammonia) are biologically active, potentially toxic compounds. Although the substrate-specificity of these enzymes and their sensitivity to enzyme inhibitors is well-known, their physiological and pathophysiological role is not cleared yet. Therefore, as a continuation of our former experiments, we investigate their function in neuropathic, postoperative and inflammatory pain conditions.

Co-supervisor: ACZÉL, Timea

Orofacial pain and primary headache disorders are among the most debilitating pain conditions. Due to several therapy-resistant patients, the therapy of migraine is far from being optimal, and it is still an unmet medical need. Therefore, understanding the pathophysiological mechanisms is crucial to identify key mediators and determine novel therapeutical targets. Thus, we investigate the role of different potential target molecules in pain models using pharmacological tools (agonists, antagonists) and gene-deficient mice. In our experiments, we investigate different reactions with vascular imaging and behavioural studies, using chemical or electrical activation of the trigeminovascular system.

Co-supervisor: Dr. HORVÁTH, Ádám István

TRPA1 and TRPV4 receptors are expressed on capsaicin-sensitive sensory neurons, immune cells and keratinocytes. TRPA1 receptors are activated by pungent agents (mustard oil, cinnamaldehyde), exogenous and endogenous toxic chemicals, as well as inflammatory mediators and noxious cold (<17°C). The activation and sensitization mechanisms and interactions of TRPV4 are less known. Therefore, we aim to analyze their roles and cross-talks in inflammatory and neuropathic pain models with thermo- and mechanonociceptive testing methods using gene-deleted mice pharmacological interventions.

Measurement of the noxious heat threshold is a new concept in the investigation of heat-induced pain, i.e. thermonociception in awake animals. Conventional methods of thermonociception measure the latency (i.e. time) of pain-avoiding (nocifensive) behavioral reactions evoked by a suprathreshold heat stimulus. In contrast, with the recently developed increasing-temperature water bath it is possible to measure the noxious heat threshold of the hind paw or tail in rats or mice by determining the lowest bath temperature that can evoke a nocifensive reaction. This novel equipment has been validated in several experimental models in which heat hyperalgesia manifested itself as a decrease of the noxious heat threshold. Future work aims at investigating other paradigms associated with a drop of heat threshold and revealing their mediators as well as pharmacological modulation including testing of analgesics.

Co-supervisor: Dr. BÖRZSEI, Rita Judit

Signal transduction is a key to understanding pathomechamisms of various diseases. Signaling pathways are often based on the formation of complexes between protein partners. In many cases, experimental determination of atomic resolution structures of protein complexes (required by drug design) is difficult. In the present project, we will calculate the structure of such complexes using computational tools. We will also study their molecular dynamics to understand their role in signaling and provide starting information for drug development.

Co-supervisor: Dr. ZSIDÓ, Balázs Zoltán

Epigenetics plays an important role in the pathomechanisms of various diseases. Modifications of histone proteins of the nucleosome, the “histone code” is fundamental in understanding of diseases with epigenetic background. In this project, we will study the effect of the modifications on structure and interactions of histones focusing on their role in disease pathomechanisms. Structural bioinformatics tools will be applied in our investigations.

Co-supervisor: Dr. POZSGAI, Gábor

Among other members of the TRP receptor family, capsaicin-sensitive sensory neurons express Transient Receptor Potential Ankyrin 1 (TRPA1) ion channels. TRPA1 can be activated by several exogenous and endogenous chemical stimuli, such as pungent agents (mustard oil, cinnamaldehyde, allicin) and toxic gases (acrolein, formaldehyde) resulting in the release of inflammatory peptides (SP, CGRP). Hydrogen-sulphide (H2S) is an important gaseous mediator of the human body. In the recent years, there have been several data published, indicating that H2S may be involved in various vascular and inflammatory processes. Moreover, it has also been suggested that H2S may act on capsaicin-sensitive peptidergic neurons. The aim of our investigation is to reveal the interaction of neural and non-neural TRPA1 receptors and H2S in microcirculatory processes, in dermal, intestinal and airway inflammations, as well as in neuropathic states, with the help of in vivo and in vitro experimental methods.