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Biochemistry and Bioorganic Chemistry
Doctoral Programme,
Faculty of Food and Biochemical Technology
The aim of this programme is to prepare highly qualified professionals capable of independent scientific work, who will be involved in the implementation of new visions and methods in practice or will continue their scientific work at universities and scientific institutes and thus contribute to clarifying the functional principles of living organisms. The programme Biochemistry and Bioorganic Chemistry was created by merging two fields of chemistry. In this way, it will educate specialists preferentially oriented either to biochemistry or to bioorganic chemistry. The common denominator of both fields is to identify the chemical nature of important processes in living organisms, to study the relationship between the structure and biological activity of biopolymers, as well as natural organic compounds or their synthetic analogues. CareersGraduates of this programme are able to apply their knowledge in various fields such as biochemistry, cell biology and molecular genetics, microbiology, organic chemistry and chemistry of natural compounds (in relation to the dissertation topic). Based on the acquired knowledge, the student is able to plan the research project independently, critically assess the risks of the proposed procedures and apply innovative research methods. Another acquired competency of the graduate is the pedagogical and managerial experience due to involvment in teaching of bachelor and master programs, primarily in the role of assistants in laboratory courses and consultations of bachelor and master theses. Theoretical, experimental, pedagogical and managerial experience predispose the graduates to creative scientific and research activities, which is increasingly sought at various institutions of the institutes of the Academy of Sciences of the Czech Republic, universities, medical facilities, pharmaceutical companies and state and private research laboratories in the Czech Republic and abroad, dealing with problems in the field of biochemistry and bioorganic chemistry. Programme Details
Ph.D. topics for study year 2026/27Aktivně cílené samouspořádané systémy
AnnotationThe present dissertation deals with the synthesis, characterization, and in vitro testing of self-ordered molecules forming nanoparticles (micelles/liposomes) with a hydrophobic core and hydrophilic parts of the molecule. The hydrophilic part of the molecule will be functionalized with functional groups affecting the surface charge of the nanoparticle and functional groups actively targeting e.g., tumors. The core of the nanoparticle will contain therapeutic drugs which will be delivered directly into the intracellular compartments. In this work, the low molecular weight agents prepared in this way with different functionalities on the hydrophilic part of the chains will be combined to achieve the best therapeutic effect. The scope of the thesis will be organic synthesis, and physicochemical characterization. The thesis involves the use of animal/human cell lines in performing basic in vitro techniques with which the student will be familiar. Pokročilé funkční polyelektrolytové filmy pro antibakteriální aplikace
AnnotationAntibacterial surfaces are increasingly important for reducing microbial contamination and infection risks in healthcare, food processing, and related industries. With the growing challenge of antimicrobial resistance and persistent surface contamination, there is a strong demand for durable, biocompatible, and environmentally safe antibacterial coatings. Current technologies include passive surfaces that prevent adhesion and active surfaces that kill microbes on contact, though achieving long-lasting, biocompatible, and environmentally safe performance remains a challenge. This PhD project focuses on the development of advanced polycation-based polyelectrolyte antibacterial surfaces using the layer-by-layer (LbL) assembly technique, which enables precise control over film thickness, composition, and functionality. The project will investigate various types of positive charges in polycation layers and their influence on film structure, stability, and antibacterial performance. In addition, the integration of biologically active agents such as enzymes and antimicrobial peptides into LbL films will be explore to create the coatings with long-term, synergistic anti-adhesive and active antibacterial functionality. Bioaktivní povlaky na bázi vícevrstevnatých polyelektrolytických filmů syntetických polykationtů s nestálým nábojem pro uvolňování terapeutických proteinů.
AnnotationIn biomedical applications, the release of growth factors (proteins) promoting vascularization from biomaterial surfaces is a key factor that supports the integration of biomaterials with the recipient tissue. An effective technique for the preparation of ultrathin coatings is the layer-by-layer technique ("LbL"), which is mainly used in engineering applications. The project aims to develop bioactive LbL films consisting of “charge-shifting” polycations based on poly(dimethylaminoethyl acrylate) (PDMAEA) and the polyanion heparin, which will release the growth factors VEGF and FGF-2 that stimulate vascular cell growth. The gradual change in charge on the PDMAEA polymer will allow tuned decomposition of LbL films and thus controlled release of immobilized growth factors. Doctoral studies will include: 1. Study of the synthesis of PDMAEA and its statistic copolymers by RAFT polymerization, with the aim to obtain polycations with different charge content and hydrolytic stability. 2. Study of the dynamics of film formation and characterization of physicochemical and morphological film properties using advanced instrumental techniques such as surface plasmon resonance (SPR), quartz crystal microbalance (QCM-D), AFM, or CLSM. 3. Preparation of real LbL films using an automated coater for layer deposition and study of in vitro protein release as a function of composition and stability of LbL films. 4. Evaluation of the cytocompatibility of LbL films and the bioactivity of released proteins in collaboration with biologists. The interdisciplinary topic focuses on polymer chemistry and biomedical applications and is suitable for graduates of chemical disciplines, such as macromolecular chemistry, physical chemistry, biochemistry, etc. Biokatalytická příprava konjugovaných polyfenolů
Annotation"The regioselective conjugation of biologically active polyphenols is a key process in their metabolism in plants and in the human body, but it remains insufficiently researched. For a detailed study of biotransformation pathways, precisely defined conjugated phenolic derivatives are necessary, which serve as analytical standards and as models for evaluating their biological activity. Many of these conjugates are not commercially available, and their chemical synthesis is complicated due to the structural complexity of the starting natural substances. Enzymatic methods therefore represent an attractive, simple, and selective tool for their preparation. Currently, however, only a limited set of bacterial or fungal enzymes are known, while the enzymatic synthesis of many types of glycosides or glucuronides has been minimally explored. The aim of the doctoral thesis is to identify, heterologously express, and characterize new enzymes suitable for regioselective conjugation of polyphenolic compounds. Candidate enzymes will be selected based on literature data and bioinformatic analysis of nucleotide sequences (GenBank) and subsequently expressed in Escherichia coli or Pichia pastoris microbial systems. Purified enzymes derived from bacterial, fungal, or plant sources will be studied for substrate specificity and synthetic capabilities. For selected enzymes with promising synthetic potential, rational design variants with increased synthetic activity towards selected natural substances (flavonoids, cannabinoids, phenolic acids) will be proposed using molecular modeling and implemented using targeted PCR mutagenesis methods. The enzymes obtained in this way will be applied to the preparation of defined glucuronides and other glycosides (e.g., rhamnosides, rutinosides, xylosides) from natural polyphenols and their polyhydroxylated metabolites. Biochemická regulace složení mateřského mléka u gestačního diabetu
AnnotationThis PhD project focuses on understanding how maternal metabolism and gestational diabetes mellitus (GDM) influence the biochemistry of human milk production. The student will study the physiological and metabolic mechanisms underlying lactation, with an emphasis on lipid synthesis, transport, and secretion in the mammary gland. Experimental work will involve comprehensive analysis of human milk samples using liquid and gas chromatography coupled with mass spectrometry (LC-MS and GC-MS) to characterize lipid and metabolite composition. Metabolic tracing with non-radioactive deuterated water (2H2O) will be used to assess de novo lipogenesis and identify tissue sources contributing to milk lipids. Comparative analyses of saliva will explore its potential as a non-invasive marker of maternal metabolic status. Through integration of biochemical data with clinical and physiological parameters, the project will reveal how metabolic control during pregnancy shapes milk composition and lactational function. Biomimetické fibrinové povlaky obohacené glykosaminoglykany a peptidy pro podporu endotelizace a hemokompatibility vaskulárních implantátů
AnnotationThe long-term success of vascular implants, particularly coronary and neurovascular stents, critically depends on rapid restoration of a functional endothelial layer on their surface. Insufficient or delayed endothelialization substantially increases the risk of thrombosis, inflammation, and restenosis, representing one of the primary clinical challenges associated with current endovascular interventions. The aim of this PhD thesis is to develop a new generation of bioactive, hemocompatible coatings that mimic natural vascular healing processes and provide a unique combination of low thrombogenicity, anti-inflammatory properties, and active stimulation of endothelial growth. The research will focus on fibrin coatings produced through controlled polymerization directly on implant surfaces, which will be subsequently functionalized with sulfated glycosaminoglycans (e.g., heparin, fucoidan, hyaluronic acid) and synthetic peptides promoting wound healing. Fibrin serves as a biomimetic matrix capable of binding, stabilizing, and presenting bioactive molecules in a form similar to that found in the early phases of vascular wound healing. The PhD candidate will optimize fibrin polymerization parameters, tune coating morphology and thickness, and introduce bioactive motifs via specific covalent conjugation strategies, including modern bio-orthogonal click chemistries. The work will involve comprehensive structural and chemical characterization using AFM, SEM, confocal microscopy, FTIR-ATR, and SPR. Coatings will be evaluated using hemocompatibility assays (coagulation activation, platelet and complement activation), anti-inflammatory assessments (macrophage adhesion, M1/M2 polarization, cytokine release), and detailed endothelialization studies. These will include static and dynamic endothelial cell seeding, migration assays, proliferation analyses, and characterization of endothelial markers such as CD31, VE-cadherin, vWF, and eNOS. The expected outcome of the PhD thesis is a fully characterized multifunctional coating that accelerates endothelial regeneration while suppressing thrombosis and inflammation, thereby addressing key limitations of current vascular implant technologies. The candidate will obtain extensive expertise across macromolecular chemistry, surface biofunctionalization, materials characterization, cell–material interactions, hemocompatibility, and advanced microscopy, providing a strong foundation for future research or industrial careers in biomaterials and regenerative medicine. Funkční a strukturní analýza enzymů zapojených do biosyntézy terpenoidů u hmyzu
AnnotationTerpenoids are the most abundant and diverse class of natural products. In many species, terpenoid secondary metabolites are vital in communication and defense. They have also been widely exploited as pharmaceuticals, cosmetics, and in the food and flavour industries, which has been driving the research on terpenoid biosynthesis in plants and microorganisms. Among animals, terpenoids are present predominantly in insects, which generally lack homologous terpene synthases. Instead, several cases of terpene synthase activity arising from duplicated isoprenyl diphosphate synthase genes have been reported. Within this PhD project, the student will search genomic and transcriptomic datasets of selected economically important insect species for candidate terpene synthase genes. The student will employ heterologous expression in various expression systems for functional characterization of the candidates, and will identify structural features linked with enzymatic activities in the characterized enzymes. The PhD project will be carried out as a part of a wider research project funded by the Ministry of Education, Youth, and Sports (INTER COST, 2024-2027). Glycinové alkoxyaminy pro nove metodiky biokonjugace
AnnotationWe just accomplished approaches to glycine alkoxyamines, which hold large promise in bioconjugation. With this project the potential of these non-natural amino acid derivatives for approaching new peptide architectures will be explored. Inovativní povlaky biomateriálů se simultánním antimikrobiálním a regeneračním účinkem
AnnotationOne of the key problems in modern medicine is tissue damage caused by acute and chronic diseases, injuries, and developmental defects. This issue is often addressed using biomaterials in the form of implants, wound dressings, and other medical devices. Therefore, a crucial task is to develop a material that resists colonization by microorganisms and inhibits biofilm formation while actively promoting integration into the surrounding tissue and accelerating healing. To achieve this dual effect, we will use two basic strategies: (1) releasing bioactive substances and (2) creating specific material topographies. Regarding bioactive substances, our study will focus on relatively simple, long-known silver ions in a new, unexplored topographical arrangement. Preliminary results suggest that when silver nanoparticles are anchored in microdomains on a polymer surface, human cells can colonize the material while the surface exhibits an antibacterial effect comparable to or greater than that of surfaces with continuous silver coverage. We will optimize the size, shape, and spacing of these microdomains to maximize the antimicrobial effect while ensuring the highest possible adhesion, viability, metabolic activity, proliferation, differentiation, and phenotypic maturation of bone, skin, and mucosal tissue cells. We plan to use this technology to modify the surfaces of orthopedic and dental implants, devices, and wound dressings. Other promising materials with great potential are MXenes, particularly titanium carbides. Preliminary results indicate that these coatings can control the degree of osseointegration and osteogenic differentiation of cells through relatively simple surface functionalization with carboxyl or amino groups. We will apply MXenes to titanium and its alloys, which are used in orthopedics and dentistry, in both planar and 3D-printed forms, and we will study their osteogenic, vasculogenic and antimicrobial potential. Spojení hmotnostní spektrometrie a separačních technik pro komplexní charakterizaci metabolomu a lipidomu v experimentálních a klinických studiích
AnnotationOver the last decade, mass spectrometry-based metabolomics and lipidomics have become central platforms for the comprehensive profiling of polar metabolites, volatile and semi-volatile compounds, and complex lipids in biological samples, including plasma, serum, urine, and tissues. The combination of chromatographic separation techniques with mass spectrometry, particularly liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS), enables complementary coverage of chemically diverse metabolite and lipid classes and remains essential for high-confidence metabolome and lipidome characterization. Despite major methodological advances, comprehensive and systematically organized metabolomic and lipidomic datasets from biofluids and tissues that are readily accessible and reusable across studies remain limited. This Ph.D. project aims to develop and apply integrated LC-MS- and GC-MS-based strategies for comprehensive characterization of the metabolome and lipidome in biological samples. The project will focus on (i) combining targeted and untargeted analytical workflows, (ii) expanding and curating mass spectral libraries to improve metabolite and lipid annotation, and (iii) applying bioinformatics and visualization tools for robust interpretation of metabolomics and lipidomics data in experimental and clinical contexts. The work will be conducted at the Institute of Physiology of the Czech Academy of Sciences and financially supported by grants from the Ministry of Education, Youth and Sports (MŠMT), the Czech Health Research Council (AZV), and the European Union’s Horizon Europe program. Interakce mezi glykomimetiky a receptory Siglec v terapii rakoviny
AnnotationAbnormal glycosylation is a characteristic feature of tumor cells that allows tumors to escape the immune surveillance. One of the key immune checkpoints in this process are Siglec lectin receptors on immune cells, which recognize hypersialylated surface glycans on tumor cells. A promising therapeutic strategy is to inhibit this process using targeted multivalent glycomimetics that bind to Siglec receptors, thereby preventing the immunosuppressive response to the tumor. This strategy may be used, for example, in patients who currently do not respond to existing immunotherapies. In the frame of this thesis, complex oligosaccharide ligands of Siglec receptors will be prepared by sequential chemoenzymatic synthesis using selective glycosyltransferases. They will be tested for affinity to recombinant receptors and subsequently in studies with immune and tumor cells and, if applicable, with tumor spheroids. This work at the intersection of glycobiology, biochemistry, and immunooncology combines methods of chemoenzymatic synthesis and characterization of oligosaccharides, production of recombinant proteins in both E. coli and mammalian cells, immunochemical methods, and, if the work proceeds well, biological methods. Světlo konvertující paramagnetické nanočástice pro detekci beta buněk pankreatu a magnetickou rezonancí in vivo
AnnotationAccurate methods to detect pancreatic ?-cell mass and functionality in vivo are essential to better understand the pathogenesis of diabetes associated with pancreatic ?-cell deficiency and to develop new treatment options. Therefore, we will develop polymer-coated paramagnetic core-shell upconversion nanoparticles (UCNPs) conjugated with small GLP-1 receptor ligands (GLP-1 peptide, liraglutide or agonist 3) to target and monitor pancreatic ?-cell mass using magnetic resonance imaging (MRI) and luminescence. The newly developed UCNPs will be optimized in size to penetrate blood capillaries of the native and transplanted pancreatic islets and modified for long-term monitoring. Ultrasmall UCNPs (5 nm) will serve as a contrast agent for electron microscopy to visualize and count mtDNA nucleoids in ?-cells, which are typically reduced in diabetes. The specificity, safety and efficacy of all developed UCNPs will be validated in in vitro and in vivo models using multimodal imaging including luminescence, MRI and electron microscopy. See Ref. doi: 10.1021/acsami.2c04274. Methakrylamidové a akrylamidové kopolymery citlivé na vnější podněty: pokročilé systémy pro dopravu léčiv a diagnostik
AnnotationPolymeric micelles and nanoparticles are studied in the field of drug delivery and targeted drug release, especially in anticancer therapy. Thanks to their size (20-1000 nm), they accumulate in tumors due to the enhanced permeation and accumulation (EPR) effect. They protect incorporated drugs during transport and help to solubilize poorly soluble drugs. The potential thermoresponsive behaviour of the polymers used avoids the complicated techniques common to the preparation of micelles and other nanoparticle-based systems. The presence of suitable hydrolytically labile groups in the structure of the polymers can be exploited to ensure the gradual degradation of the nanoparticles and to ensure excretion of the polymer from the organism. With the intention of preparing nanoparticles with thermoresponsive and pH-sensitive properties, amphiphilic diblock copolymers consisting of a fully hydrophilic block, e.g., poly[N-(1,3-dihydroxypropyl)(meth)acrylamide] and an amphiphilic block, e.g., poly[N-(2,2-dimethyl-1,3-dioxan-5-yl)(meth)acrylamide], will be prepared by controlled radical RAFT polymerization. The associative behaviour of the copolymers in aqueous solutions, the formation and disintegration of nanoparticles or micelles will be studied by various physicochemical methods, e.g. size-exclusion chromatography, dynamic light scattering, NMR and transmission electron microscopy. The proposed systems offer the possibility to transport in particular anticancer drugs. Molecular mechanism of hepatoprotective and hepatotoxic effects of common dietary supplements
AnnotationUp to 50% of adults in Europe and the US utilize herbal-based dietary supplements, a multi-billion dollar industry that continues to grow. However, the safety of these preparations is a critical concern, as many are potentially hepatotoxic and linked to Herbal and Dietary Supplement Induced Liver Injury (HDSILI). Silymarin, an extract of Milk Thistle (Silybum marianum L.), is a leading supplement frequently used by patients with the Metabolism-Associated Steatotic Liver Disease (MASLD), a condition affecting approximately 30% of the Western population. Despite its widespread use, the efficacy of silymarin in preventing liver disease progression is controversial. Recent findings by the project partners indicate that commercial extracts often suffer from low bioavailability of active substances and significant contamination with mycotoxins and tropane alkaloids. Therefore, research defining the parameters for safe and efficient silymarin products is urgently needed. The primary objective of this Ph.D. project is to investigate Endoplasmic Reticulum (ER) stress as a molecular mechanism underlying MASLD progression. Specifically, the study will analyze how ER stress is modulated by the complex interplay between silymarin components and common contaminants. Nanoparticles for radiodynamic therapy of hypoxic prostate cancer
AnnotationProject under dual supervision - cotutelle with Open University of Catalonia, Spain. Financed by HORIZON-MSCA-DN. Objectives: To develop a radiosensitizing nanosystem for external beam radiation therapy of prostate cancer under hypoxic conditions. Upon X-ray irradiation, the proposed nanoparticles will increase the intracellular reactive oxygen species concentration thus destructing the tumor cells. P-Chirální fosfiny jako asymetrické organokatalyzátory
AnnotationRecently we discovered new P-chiral ligand architectures, which were successfully applied as ligands in asymmetric gold catalysis. In general, phosphines are at the same time useful organocatalysts in a number of reactions. With this project the potential of our P-chiral phosphines in asymmetric organocatalysis will be explored such as cycloadditions, Michael additions, allylic substitution or umpolung reactions. Polyelektrolytické částice pro uvolňování růstových faktorů podporujících vaskularizaci polymerních nosičů v bioaplikacích.
AnnotationIn tissue engineering, vascularization of polymer scaffolds developed for tissue replacement is crucial for their functionality in the recipient body. Direct administration of free pro-angiogenic proteins (e.g., VEGF or FGF-2) often fails to produce effective results. Polymer-based delivery systems, such as nano- and microparticles, enabling controlled and localized release of growth factors, are therefore intensively studied. The PhD project aims to develop polyelectrolyte nano- and microparticles based on charge-shifting poly(dimethylaminoethyl acrylate) (PDMAEA) polycations for the controlled growth factor delivery. The gradual loss of charge on PDMAEA enables controlled particle degradation, sustained release of growth factors, and reduced toxicity, making these systems attractive for biomedical applications. The doctoral research will focus on i) the synthesis of PDMAEA-based block copolymers via RAFT polymerization to tune the particle charge density and corona composition, ii) the preparation of polyelectrolyte particles and characterization of their physicochemical properties (DLS, zeta potential measurements, IR spectroscopy, ITC, TEM), iii) investigation of protein loading and release behavior using ELISA, and iv) the evaluation of particle biocompatibility and protein bioactivity in collaboration with biologists. The interdisciplinary topic focuses on polymer chemistry and biomedical applications and is suitable for graduates of chemical disciplines such as macromolecular chemistry, physical chemistry, biochemistry, etc. Polymerní nosiče kationtových detergentů pro bezpečnou antibakteriální terapii
AnnotationBacterial infections, particularly those of the biofilm type, represent an increasing challenge for modern medicine, primarily due to rising antibiotic resistance. Cationic amphiphiles are highly effective local bactericides; however, for practical use on wounds, mucosal surfaces, or technical materials, it is often more advantageous to apply them not as concentrated solutions but in the form of controlled-release systems. Such formulations enable the long-term maintenance of lower, yet still bactericidal, concentrations of these agents, which are no longer harmful to human tissues. The aim of this doctoral dissertation is to prepare amphiphilic polyanions with varying structures and charge densities designed for the encapsulation and controlled release of micelles of cationic bactericides. The work will focus on elucidating the relationships between the structure of the polyanion and the bactericide, the efficiency of supramolecular encapsulation based on Coulombic interactions, the structure of the resulting polyplexes, and the release kinetics of the active component as influenced by temperature, ionic strength, and pH, as well as the associated bactericidal effects. A broad range of physicochemical methods will be employed to characterize these systems, including scattering techniques, fluorescence spectroscopy, isothermal titration calorimetry, and biological assays of antibacterial activity. Polymerní koloidy jako speciální nosiče pro transport biologicky aktivních látek nosní dutinou
AnnotationThe project is focused on the development, synthesis and characterization of novel polymer particles in colloidal form for therapeutic and diagnostic purposes via intranasal administration. The particles will be prepared by heterogeneous polymerisation techniques (dispersion or precipitation) and the main polymerisation reaction will be based on an aromatic substitution mechanism. Bioanalogic substances derived from aromatic structures of plant and animal origin will be used as monomers. The influence of reaction conditions on the morphology and composition of polymer particles and other physicochemical parameters determining the behaviour of polymer particles in biological environments will be studied. Subsequently, the particles will be derivatized for their detection using preclinical imaging methods so that their biodistribution and pharmacokinetics can be monitored after intranasal administration. Biological testing of the particles will be performed at the collaborating departments of the UEM CAS and the 1st Faculty of Medicine of the Charles University. The aim of this collaboration is to describe how the composition and morphology of the particles from the new polymer types affects the mechanism of each type of intranasal delivery further into the body. The researcher will be based in the laboratories of the Institute of Macromolecular Chemistry at the BIOCEV Biotechnology Centre. Polymerní teranostické systémy pro zobrazování inzulin-produkujících buněk a léčbu diabetu
AnnotationType 2 diabetes is a serious metabolic disorder characterized by insulin resistance and the gradual failure of pancreatic ?-cells, leading to chronic hyperglycemia and the subsequent development of severe vascular, metabolic, and hormonal complications. Modern therapies employing GLP-1 agonists (e.g., liraglutide, semaglutide, or dulaglutide), which activate GLP-1 receptors on the surface of ?-cells, significantly improve glycemic control. However, their efficacy is limited by a short circulation half-life, rapid proteolytic degradation, and suboptimal receptor interaction, necessitating frequent dosing. The aim of this project is to develop innovative conjugates of GLP-1 peptide agonists with biocompatible polymeric carriers that provide prolonged therapeutic action, enhanced stability, and more efficient interaction with GLP-1 receptors on target cells. The project also includes the integration of imaging-enabled structural motifs to allow monitoring of conjugate biodistribution and quantification of labeled ?-cells using magnetic resonance or fluorescence-based techniques. Key emphasis will be placed on the rational design, synthesis, and detailed physicochemical characterization of water-soluble polymers based on phospho- and fluorinated polymer platforms, as well as their selective conjugation to GLP-1 agonists. The resulting conjugates will be evaluated in collaboration with domestic research partners (IKEM, FGÚ AV ČR) through both in vitro and in vivo studies, with the aim of monitoring pancreatic ?-cell populations and assessing the conjugates’ ability to effectively stimulate insulin production. Radioaktivní a fluorescenční značení polymerů a nanočástic pro medicínu a preklinické testování.
AnnotationThis doctoral thesis focuses on the development and optimization of labeling techniques for polymers and nanoparticles in the field of medicine. The labeling allows for tracking and provides valuable information for therapy and next biological testing. The main objective of this work is to develop methods for radioactive and fluorescent labeling of polymers and nanoparticles. Redox mechanisms of insulin secretion
AnnotationThe central role of pancreatic beta cell, insulin secretion, is still not fully understood, concerning molecular mechanisms. We have revealed that redox (H2O2) signal is essential for glucose-stimulated insulin secretion (GSIS, the source is NADPH oxidase 4, NOX4) and fatty acid-stimulated insulin secretion (FASIS, the source are mitochondria). The concomitant metabolic pathways are not yet completely characterized for all insulin secretagogoues, e.g. for branched-chain amino acids and others. Therefore, we will develop mitochondria-specific metabolomics and proteomics after rapid magnetic separation of mitochondria having HLA antigen expressed on the surface of their outer membrane. Islets will be isolated from the respective transgenic mice. Using 13C-metabolites, we will study the respective metabolic pathways as well as redox homeostasis in physiological and simulated diabetic (pathological) conditions. We will also judge conditions for lipotoxicity and role of lipid metabolism. See Ref. doi: 10.1016/j.redox.2024.103283 and doi: 10.2337/db19-1130. Výzkum cílených radiomodulátorů a buněčné odpovědi na radiaci
AnnotationThe aim of this Ph.D. project is to develop a new generation of radiosensitizers and radioprotectants (targeted polymer conjugates as well as small molecules) with applications in modern oncology and in extreme conditions, such as interplanetary expeditions. The student will address a complex, interdisciplinary topic at the interface of organic/polymer chemistry and tumor biology. The project is best suited for candidates interested in organic/polymer synthesis who are not afraid to cross into biology, who have strong analytical thinking skills, and who are eager to learn modern tissue-culture techniques. Synthesis and design: Preparation of new bioactive compounds and polymer carriers, optimization of structure–activity relationships (SAR), and advanced characterization (NMR, LC–MS/HPLC). Radiobiology and 3D models: Testing of compounds in relevant models, with an emphasis on 3D tumor spheroids that mimic the real tumor microenvironment, including hypoxia and nutrient gradients. Mechanistic studies: Quantitative assessment of viability, visualization of compound penetration and cell death using confocal microscopy, and analysis of key pathways (DNA repair, senescence, mitochondrial stress). Self-cleaning anti-biofilm polymer surfaces
AnnotationThe formation of bacterial biofilms is a one of the major issues in the current biomedical research. In the body, such biofilms are created on the surface of the medical devices, e.g., joint prostheses or heart valves, where they cause inflammation and chronic infections. The aim of this Ph.D. project is to develop a novel class of smart self-cleaning antibiofilm polymer surfaces, based on poly(2-alkyl-2-oxazoline)s, that are both anti-fouling and able to catalytically prevent the biofilm formation in the very long-term period. The project work includes polymer synthesis, the surfaces preparation and the study of their physicochemical properties. Moreover, the selected surfaces will be subjected to comprehensive in vitro and in vivo testing in the collaboration with biologists. Stabilní dusíkaté heterocyklické radikály pro syntézu inhibitorů vápníkových iontových kanálů
AnnotationThe efficient and versatile synthesis of nitrogen-rich scaffolds requires continuous development, given their relevance to medicinal chemistry and chemical biology. In this project, we explore the synthetic utility of stable N-heterocyclic radicals to uncover a novel chemical space. The pharmacological profile of the synthesized molecules will be assessed using patch-clamp electrophysiology of calcium ion channels to develop new molecules with analgesic properties. Supramolekulární polymerní systémy citlivé na vnější podněty pro biomedicínské aplikace
AnnotationSelf-assembly of (macro)molecules is of crucial importance in the architecture of living organisms. Supramolecular systems have their key properties critically dependent on self-assembly and find use in the area of biomedical applications especially if they are able to reversibly react to external stimuli (changes in pH, light, redox potential, ultrasound, temperature, concentration of certain substances). The doctoral thesis will be based on chemical and/or physicochemical preparation and study of self-assembly of such multi-stimuli-responsive nanoparticles with external environment (pH, redox potential and temperature responsiveness); the exact topic will take into account the student´s interests. The studied nanoparticles and injectable depot systems will be designed for diagnostics and personalized immunoradiotherapy and immunochemotherapy of cancer and autoimmune diseases. Optimized nanoparticles will be then provided to collaborating biological workplaces for in vivo testing. Synthesis and Application of Silica-Coated Quantum Dots in Bioengineering
AnnotationQuantum dots (QDs) are semiconductor nanoparticles with outstanding optoelectronic properties. More specifically, QDs are highly bright and exhibit wide absorption spectra, narrow light bands, and excellent photovoltaic stability, which make them useful in bioscience and medicine, particularly for sensing, optical imaging, cell separation, and diagnosis. In general, QDs are stabilized using a hydrophobic ligand during synthesis, and thus their hydrophobic surfaces must undergo hydrophilic modification if the QDs are to be used in bioapplications. Silica-coating is one of the most effective methods for overcoming the disadvantages of QDs, owing to silica’s physicochemical stability, nontoxicity, and excellent bioavailability. Micro and nano-particles of SiO2 will be covered by polydopamine, or by mixture of citric acid and urea, or by melamine. The covered layer will be carbonized in the presence of conducting metal ionically connected to the covered layer. The entire SiO2 can be dissolved. Rest hollow charged particles will be examined by electrochemical, fluorescent methods and other techniques needed for characterization of quantum dots. Synthesis of glycomimetics for targeted therapeutic applications
AnnotationCarbohydrates are essential biomolecules that play a crucial role in various biological processes, such as cell signaling, adhesion, recognition, and intercellular communication. In the context of biomedicine, carbohydrates and their derivatives represent important targets for the development of new therapeutic agents. Glycomimetics are synthetic analogs of carbohydrates that mimic their biological functions; however, unlike natural carbohydrates, they are stable against chemical and enzymatic hydrolysis, enhancing their therapeutic potential and applicability. The aim of this doctoral project is to design, synthesize, and characterize new glycomimetic structures with potential applications in targeted therapy and diagnostics. The focus will be on developing compounds with high specificity and affinity for receptors involved in pathological processes, such as inflammation, infections, and tumor growth. The final glycomimetics will undergo biological testing to evaluate their therapeutic and diagnostic potential. This topic is primarily intended for graduates of chemistry or pharmaceutical fields. Throughout the project, the student will acquire in-depth knowledge of organic synthesis, separation and purification techniques, and modern structural analysis methods (NMR, MS, HPLC). The project will also include basic biological evaluation of the synthesized compounds. Syntéza a aplikace polymerních lapačů interagujících s kationtovými amfifilními peptidy kompenzací náboje.
AnnotationBiocompatible polymer ions have been intensively studied as promising materials in the therapeutical and diagnostical fields of nanomedicine. Recently, it was demonstrated that polyanions with a high charge density are able to suppress the biological effects of the cationic amphiphilic peptide (CAMP) melittin from bee venom by binding it to the polyplex complex. In the future bio-inspirited nanostructures loaded by toxic drug inside release the drug in the needed place. Drug will be honey bee poison melittin. Needed place will be cancer. The cathelicidin is an element of innate immunity, that plays an important role in the development of the pathogenic process in psoriasis. Both cathelicidin and defensins are CAMPs are expected to behave similar to mellitin from the point of view of interaction with polyanions such as polyacrylic acid. Thus, scavenging these peptides by locally administered polyanions should break the cytokine storm cycle, leading to the induction of psoriasis, and thus suppress it. The series of nanogels acids will be prepared using microemulsion polymerization technique. In vitro testing (hemolysis on mouse erythrocytes) of obtained materials will be performed. Chemical, physical and biomedical investigation will be performed. Syntéza a charakterizace vysoce citlivých bimodálních senzorů rozpuštěného kyslíku pro EPR/FLIM oxymetrii
AnnotationThe project aims to the preparation and characterization of water-soluble trivalent carbon-centered radicals equipped with additional fluorescence groups for direct, noninvasive and repeatable dissolved molecular quantification, enabling also measurement in cells and vessels. The quantification of oxygen levels in-vitro and in-vivo is important not only for the understanding of physiological processes, but also in the assessment and therapy of pathological conditions such as cancer, peripheral vascular disease, inflammatory and wounds. It is extremally challenging to obtain exact oxygenation values in cells or in tissues at microscopic scale. In this project we are combining two of the best suited techniques for this purpose by creating a single bimodal molecular detector. The first oxygen detection method is based on EPR line broadening caused by paramagnetic O2 molecules tumbling in proximity of the radical and the second method is based on fluorescence quenching or fluorescence lifetime shortening due to interactions with oxygen. The two types of equipment will be used for the detection - electron paramagnetic resonance spectrometer and confocal microscopy equipped with fluorescence lifetime imaging (FLIM). The molecules will also be tested on 3D cell cultures (spheroids). Příprava a studium azadienů pro aplikaci v bioortogonálních reakcích
AnnotationThe project aims to design and synthesize diverse heterodienes, such as tetrazines, and triazium salts, and to study their reactivity with unactivated and strained dienophiles. The effect of different substituents on reaction kinetics and the compounds' potential for fluorogenic properties will be examined. The most promising candidates will be tested on model biological systems, including proteins (or other biomolecules) and cell cultures. Syntetické polymery jako alternativa proteinů pro biochemické aplikace
AnnotationSociety is increasingly seeking ways to reduce the use of animal-derived products, including proteins used in medical diagnostics. This creates many opportunities for modern synthetic macromolecules, which can replace or supplement biological proteins in various applications. As part of your dissertation, you will contribute to the development of these "artificial proteins" based on synthetic hydrophilic polymers. We are looking for motivated students interested in combining modern polymer chemistry with biochemistry to develop sustainable alternatives to natural proteins. Using advanced controlled polymerization techniques like Photo-RAFT and CuRDRP, you will design and synthesize sequence-defined polymers based on methacrylamides and (meth)acrylates. Your work will involve synthesizing polymers with controlled chain architectures and optimizing polymerization processes. You will perform detailed characterization of the materials using state-of-the-art analytical techniques (SEC, FFFF, LC MS, NMR, etc.). Additionally, you will engage in organic synthesis of new monomers and their functional derivatives. The materials you create will be tested in real biochemical applications in collaboration with both domestic and international partners, including industry. We are seeking an enthusiastic candidate passionate about macromolecular and/or organic chemistry, eager to learn across disciplines, especially biochemistry and biology. We offer exciting and diverse work within a young, dynamic team at a cutting-edge academic facility, with opportunities for internships abroad at partner institutions. Cílená radioterapie pro léćbu hypoxických nádorů
AnnotationTreatment of hypoxic tumors is complicated due to higher radio/chemo resistance resulting in the subsequently lower clinical outcome of the treatment. We propose to explore a new concept of self-assembled polymer radiosensitizers to overcome the problem low hypoxic tumor radiosensitivity. The proposed approach is based on restoration of radiosensitivity of hypoxic cancer tissue by actively hypoxia-targeted delivery of reactive oxygen species (ROS)-precursors as well as on selective decomposition of hydrogen peroxide in hypoxic tissue influencing the HIF-1 alpha system. The proposed concept utilizes hydrophilic biocompatible polymer-based carriers with hypoxia-targeting nitroaromatics systems. The doctoral thesis will be based on synthesis, chemical and/or physicochemical characterization and study of self-assembly properties of such multi-stimuli-responsive nanoparticles with external environment; the exact topic will take into account the student´s interests. The studied nanoparticles and injectable depot systems will be designed for diagnostics and personalized immunoradiotherapy and immunochemotherapy of cancer and autoimmune diseases. Optimized nanoparticles will be then provided to collaborating biological workplaces for in vivo testing. 3D tisk poly(glycerol-sebakátu) pro aplikace v tkáňovém inženýrství.
AnnotationPoly(glycerol sebacate) (PGS) is a biocompatible, biodegradable polyester with tunable mechanical properties, representing a promising alternative to non-degradable biomaterials—particularly for soft tissue regeneration and other applications requiring flexible elastomeric scaffolds. This PhD project aims to address current challenges in the 3D printing of PGS, which include optimizing the composition and viscosity of printable “inks,” developing efficient cross-linking methods, whether photo-induced or enzyme-mediated, and improving the biocompatibility of highly hydrophobic PGS through 3D printing of blended inks with biopolymers such as collagen. The student will gain experience in various synthesis techniques, 3D printing methods, and material characterization procedures using modern instrumentation (GPC, ?H and ??C NMR, UV/VIS and fluorescence spectroscopy, Cellink BioX 3D printer, electron and optical microscopy, rheological measurements). A background in polymer chemistry, organic chemistry, or biomaterials is an advantage but not a requirement — what matters most is a willingness to learn and explore new areas in these fields. 3D superrezoluční mikroskopie ultramorfologie mitochondrií
Annotation3D nanoscopy has not yet assessed mitochondrial cristae morphology, nor the internal structure of mitochondrial DNA (mtDNA) & protein complexes, termed nucleoids. Hence, we’ll survey 3D-redistribution of cristae and their shaping proteins or nucleois employing our prototype Vutara 3D superresolution microscope for stochastic techniques such a PALM and dSTORM. We will conduct studies under physiological situations vs. pathology (type-2 diabetes, cancer) using dSTORM with nanobodies or FRET excited PALM/dSTORM. Thus nm changes will be reflected by novel 3D nanoscopy methods. Also mtDNA nucleoids will be studied at increased and diminished mitochondrial biogenesis, while applying own mitoFISH nanoscopy for D-loop counting. Artificial manipulations of nucleoid size and mtDNA content will be studied as well as nucleoid division. Results will be translated into specific protocols for 3D nanoscopy, specifically developing novel relevant 3D image analyses based upon the Ripley’s K-function and Delaunay algorithm. Molecular cell biology will thus be combined with up-to-date 3D nanoscopy. Note, the molecular biology techniques will be conducted and be ready for the applicants by the coworkers of the Department No.75. See Ref. doi: 10.1089/ars.2022.0173. |
Updated: 20.1.2022 16:26, Author: Jan Kříž