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PhD topics for academic year 2021/2022

Department of Chemistry of Natural Compounds

Faculty of Food and Biochemical Technology

Identification of new psychoplastogenic compounds through structure-activity relationship studies as potential neurochemical tools for investigating human cognition

Kuchař Martin, doc. Ing. Ph.D. ( mar...@vscht.cz)
Objectives of this research project are to discover and synthetize novel chemical compounds with potential psychoplastogenic properties to be used as tools for neuroimaging studies elucidating their underlying neurobiological mechanisms.
Using structure-activity relationship investigations of already known and described psychoactive compounds primarily of the tryptamine and phenethylamine classes, this project aims to design and develop synthetic routes for their new analogues and to identify suitable substances for pharmacological and neurobiological investigations. Their biological activity will be tested within international collaboration for their interaction with monoamine receptors and transporters, cytotoxicity, and effects on growth of neuronal cells (by monitoring the BDNF factor). Selected compounds will be subjected to preclinical studies in animal models, especially with the use of behavioral tests and imaging methods such as EEG, fMRI and in the case of isotopically labeled substances also with PET.
Faculty of Food and Biochemical Technology

Novel glycomimetics as inhibitors of galectins

Parkan Kamil, Ing. Ph.D. ( par...@vscht.cz)
Carbohydrates are structurally diverse group of natural products which play an important role in numerous biological processes, including immune regulation, infection, and cancer metastasis. Unfortunately, native carbohydrates suffer from inherently weak binding affinities and poor pharmacokinetic properties. To enhance their potential as drug candidates, glycomimetics have been developed. They are more drug-like compounds, which mimic the structure and function of native carbohydrates. However, the advancement in carbohydrate research is relatively slow due to the problems associated with the complexity of carbohydrates structures and the lack of general synthetic methods. This problem could be solved using photoinduced chemistry under catalytic conditions. The use of photocatalysis is heading towards “greener” chemistry, where enhanced synthetic efficiency through the reduction of unnecessary waste is attained.
The goal of the PhD project will be the development of synthetic methodologies for the preparation of various biologically prospective glycomimetics with affinity towards galectins (Gal-1, Gal-3, Gal-7), which are involved in many physiological functions, such as inflammation, immune responses, cell migration, autophagy, and signaling.
Faculty of Food and Biochemical Technology

Study of natural biologically active substances transport through membrane systems

Kuchař Martin, doc. Ing. Ph.D. ( mar...@vscht.cz)
Jeništová Adéla, Ing. Ph.D. ( ade...@vscht.cz)
This research work will deal with studies of biological membranes (skin, cornea, blood-brain barrier) in terms of their permeability to a number of natural biologically active substances with neuropsychopharmacological potential. Emphasis will be placed on the development and preparation of formulations containing CBD, THC derivatives and neuroactive steroids with suitable transport carriers across the skin, cornea and blood-brain barrier. The quantity of permeated substances and the changes in membranes caused by the passage of active substances and their carriers will be monitored. Commercial Franc diffusion cells will be used for the in vitro model of transdermal transport. The wok will also include the development of a new diffusion cell for transcorneal transport. The permeation of substances across the blood-brain barrier will be monitored by their pharmacological studies in the animal model with Wistar rats. An advanced separation technique coupled with mass spectroscopy will be used for the pharmacological study. Vibrational spectroscopy techniques will serve as advanced tools for the investigation of structural changes and the distribution of substances in membranes. The research will be carried out in cooperation with the International Eya Bank of Prague and the National Institute of Mental Health.
Faculty of Food and Biochemical Technology

Study of the photocatalytic degradation of organic polutants from wastewater

Kuchař Martin, doc. Ing. Ph.D. ( mar...@vscht.cz)
Cihlářová Petra, PharmDr. Ph.D. ( mik...@vscht.cz)
The work is focused on the utilization of liquid chromatography coupled to mass spectrometry to measure kinetics of photocatalytic degradation of selected biologically active pollutants in wastewater. Analytical methods elaborated in frame of the project will be further utilized for the identification of ultratrace quantities of degradation products. In silico prediction will be used to determine the degradation products and correlated with experimental data. The biological activity and possible toxicity of the products resulting from the photocatalytic degradation will be assessed in collaboration with the Institute of Experimental Medicine AV ČR.
Faculty of Food and Biochemical Technology

Synthesis and application of ligands for P2X7 receptor imaging

Jurášek Michal, Ing. Ph.D. ( jur...@vscht.cz)
In pharmaceutical chemistry, the development of ligands binding biological receptors is a major way for the introduction of new diagnostic and therapeutic agents. Positron emission tomography allows minimally invasive imaging and quantification of ligand interactions with receptors in space and time. Objective: To develop P2X7 receptor ligands of various subtypes bearing radioactive elements emmiting positrons. Additional goal: To develop P2X7 receptor ligands for single photon emission tomography and autoradiography.
For the biological and medical evaluation of the newly prepared compounds, the partner institution in Austria requested the approval of the relevant ethics committee deciding on the human application of experimental radiodiagnostics for positron and single photon emission tomography.
Development principles: 1. Vyhledejte v literatuře údaje o ligandech P2X7 receptoru
2. Vyhodnoťte nalezené literární údaje
3. Syntetizujte ligandy P2X7 receptoru pro značení radiaktivními izotopy a jejich standarty
4. Připravené sloučeniny plně popište a prostudujte jejich vlastnosti
5. Optimalizujte metodiku radiochemického značení
6. Diskutujte výsledky s údaji v literatuře a dále obecnou použitelnost
Faculty of Food and Biochemical Technology

Synthesis of molecules for detection and elimination of senescent cells

Jurášek Michal, Ing. Ph.D. ( jur...@vscht.cz)
Cells lose their ability to divide during the cell senescence stage. Senescent cells thus play a key role in the aging process of the organism. Over time, senescent cells accumulate in the body and secrete a number of inflammatory cytokines, chemokines, growth factors or proteases. They increase the susceptibility to various diseases, including tumorigenesis. The aim of the work will be (1) to synthesize new fluorescent ligands for the detection of senescent cells, (3) to synthesize new selective ligands for the elimination of senescent cells and based on feedback results (3) to design and synthesize tools for mechanistic studies of functional molecules on senescent cells.
Updated: 29.11.2019 12:30, Author: Jan Kříž

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