čas: 7.6.2020 11:45:45
Obnovit | RAW
Institute of Macromolecular Chemistry CAS
List of available PhD theses
Advanced plasmonic biosensors: towards the next-generation biomolecular interaction analysis
Life is associated with myriad of interactions that occur among a large variety of biomolecules. Hence, the understanding of biomolecular interactions and their roles in diseases represents a research goal of paramount importance. This project aims to develop a new plasmonic biosensor-based technology that will enable investigation of biomolecular interactions in complex real-world biological environments, which will advance the field of biomolecular interaction analysis beyond the current state of the art. This project focuses on the development of advanced coating technologies for plasmonic (nano)structure-based biosensors. This relies on precise covalent immobilization of biomolecules in combination with suppression of non-specific interactions from biological media, using state of the art controlled (surface) polymerization techniques and ligation reactions. The resulting biosensor technology will provide new insights into interaction of biomolecules involved in onco-hematological diseases, such as myelodysplastic syndrome and other frequently occurring hematological malignancies. The research will be conducted in collaboration with the Institute of Photonics and Electronics, and the Institute of Heamatology and Blood Transfusion in Prague.
Biodegradable polymer systems for medical applications
Biodegradable and biocompatible polymer systems show numerous applications in both human and veterinary medicine. We have recently developed and patented multiphase polymer systems based on thermoplasticized starch (TPS), polycaprolactone (PCL), titanium dioxide based nanoparticles (TiX) and antibiotics (ATB). Morphology and properties of these systems can be adjusted by their composition and targeted phase structure modification during the processing. TPS/PCL/ATB systems can be employed in treatment of strong local infections such as osteomyelitis. The project comprises preparation of the above systems (by melt mixing), optimization of their phase structure (targeted modification of processing conditions), characterization of their morphology (electron microscopy), properties (macro- and micromechanical properties), and participation in medical tests in collaboration with local hospital (FN Motol; treatment of local infects, biodegradability).
Biodegradable polyurethane foams from renewable raw-materials: synthesis and characterization
In recent years, considerable attention has been paid on polyurethanes (PU) containing structural biodegradable units of polyester-polyols. The polyols are thus often tailored with respect to a final application, while commercially available aliphatic polyisocyanates are often used as the second raw material for polyaddition. This approach enables to prepare biodegradable linear and thermoplastic PU (TPU), whereas the more-demanded crosslinked PU, biodegradable PU foams, cannot be produced due to low reactivity of aliphatic isocynates and/or ecotoxicity of their aromatic analogs. The PhD topic is focused on alternative synthetic routes of PU foams utilizing renewable (bio-based) raw-materials for synthesis of polyols and isocyanates and non-isocyanate preparation of PU foams (NIPU). The experimental work will include a synthesis of new types of monomers and PU foams and their structure-related characterization. Degradation behavior of the produced PU foams will be studied with respect to foams’ composition and structure. Biodegradation tests will be carried out in cooperation with Institute for Environmental Studies, Charles University in Prague. The PhD theme is suitable for graduates in Chemistry, especially macromolecular and organic chemistry.
Crosslinking of biopolymer composites for 3D printing
FDM 3D printing is currently a rapidly expanding area whose limitations are limiting number of thermoplastic (especially composite) materials suitable for 3D printing, which would have the desired electrical, thermal conductivity and mechanical properties. The aim of the project is to use a functional biopolymer as the curing component of the composite, which enables the shape fixation of the material in the final preparation step (after printing). The project deals with research of i) reaction and process conditions of crosslinking of biopolymers (keratin, chitin and chitosan), ii) preparation of nanofillers (e.g. graphene) in the presence of biopolymers and iii) rheological behavior of biopolymers / nanofillers systems.
Injectable biomimetic hydrogels for regenerative medicine
The in situ formed biomimetic hydrogels represent very attractive class of biomaterial scaffolds for regenerative medicine. Up to date, no injectable biomaterials that would allow full tissue regeneration are available. Development of biomaterials imitating ECM regeneration in the body would be useful for various types of surgical and orthopaedic procedures. The aim of the project is to design injectable, in situ formed hydrogels that could be used as an artificial ECM environment for matrix-assisted cell therapy and tissue regeneration. The dissertation will focus on design, synthesis and study of physicochemical properties of polymeric precursors based on synthetic polypeptides and natural polysaccharides. Furthermore, a gelation protocol will be developed to establish a hydrogel network, which could ensure mechanical protection of cells from shear forces and promote cell retention and engraftment. Hydrogels will be modified with biomimetic structures, e.g., cell-adhesion peptides that would promote specific interactions with cells and growth factors. Knowledge and skills in macromolecular and organic chemistry is expected as well as willingness to improve knowledge in biochemistry and biology. Student will learn various techniques and methods using modern measuring instruments.
Multifunctional hybrid metal-organic frameworks for Li-ion batteries and fuel-cell applications: synthesis, structure and ionic dynamics.
The development of hybrid and full electric vehicles raises the demand for electrical energy generation and storage devices. Metal-organic frameworks (MOFs) with its well-defined porous architecture that allow Li-ions to be reversibly inserted/extracted, predetermines MOFs to be explored as electrode as well as electrolyte materials for Li-batteries (LiBs). Many drawbacks however, still have to be overcome. The purpose of the proposed project is improvement of hybrid MOF materials. A possible way how to modify MOF toward the better performance in LiBs applications is utilization of metallacarborane compounds. Given their inherent robustness, electron-delocalized skeletal bonding, amphiphilic behavior and ability to accommodate metal atoms in the cage framework, metallacarboranes are perfect candidates. The project is thus focused on the synthesis of hybrid MOF systems modified by various Li salts (optionally combined with selected polymers) and subsequent optimization of their composition with respect to mechanical and physicochemical properties. Simultaneously the most promising candidates will be subjected to a range of physicochemical characterization techniques amongst them solid-state NMR spectroscopy will be particularly useful for probing structure and ionic dynamics.
NMR crystallography of active pharmaceutical ingredients
In the NMR Department of the IMC there is an urgent need for lowering the computational cost and at the same time increasing the robustness of the crystal structure prediction-based NMR crystallography approach to structural elucidation of powders and other forms of molecular solids. The project aims at analyses of the crystal-symmetry elements together with other geometry parameters in order to find and implement structural constraints and/or restraints into our NMR crystallography protocol. In addition, extensive database searches of the investigated structural motifs will be used.
Nanotherapeutics based on antimicrobial peptides for multiresistance bacteria species treatment
The work will be focused on the study of biodegradable polymeric nanomaterials carrying antimicrobial peptides. The studied nanomaterials will have a linear, branched or star-like structure composed from hydrophilic or amphiphilic copolymers containing stimuli-sensitive linkers. The aim of this work will be to develop an effective nanotherapeutic for the treatment of infections caused by resistant bacteria. The biological activity of these polymeric nanomaterials will be studied in dependence on the detailed structure of the whole system. The student will extend his/her knowledge in the area of ??preparation of mentioned nanomaterials, in vitro biochemical and biological testing and in vivo biological characterization of nanomaterials. The applicant's knowledge and experience in organic and / or macromolecular chemistry is an advantage, along with the desire to learn new things in other fields, such as biochemistry. The work assumes close cooperation with cooperating biological teams in the Czech Republic and abroad.
Optimization of Fused Filament Fabrication of Polymer Materials
Fused Filament Fabrication (also known as 3D printing) is a routine additive manufacturing technology widely used in industry, science and hobbies. Despite numerous advantages, FFF-made components often suffer from insufficient mechanical performance. The lower mechanical performance is typical of middle- and hobby-level FFF devices. Proposed research is aimed to the optimization of morphology, micro- and macromechanical properties of selected polymers prepared in three different ways: (i) by means of standard processing techniques (such as melt mixing and compression molding), (ii) by means of commercial FFF devices, and (iii) by means of modified FFF device, which could produce samples with improved mechanical properties. The modified FFF device will work with the melted filament in the environment of atmospheric-pressure plasma. Plasma serves as a source of highly-reactive species (excited radicals, molecular ions, and atomic ions). These species cause partial break of polymer chains, followed by cross-polymerization or co-polymerization if co-polymer is added. Prototype of dedicated equipment containing experimental printhead and RF power generator for plasma generation will be developed during the project in order to investigate feasibility for practical application.
Physicochemical and biological properties of nanoparticles made of amphiphilic copolymers with different architectures
The aim of the project is to compare physico-chemical and biological properties of nanoparticles prepared by self-organization of various amphiphilic copolymers in aqueous milieu; the thesis is expected to answer the question if we should prefer block or gradient copolymer for purposes of biomedical applications. The ability of the nanostructures to encapsulate active molecules will be assessed, for instance therapeutic compounds, imaging agents, or inorganic probes. Exploited characterization techniques include UV/VIS spectrometry, fluorescence spectroscopy or fluorescence correlation spectroscopy; finally, the biological properties of the prepared systems will be tested in vitro and in vivo in collaborating biological laboratories. The topic is multidisciplinary and might be further adjusted according to the individual interests of a student. If the student is interested in, it is possible to make part of the study at collaborating workplace in France within the program “double degree PhD”, the deadline is February 14, 2020 (see https://studium.ifp.cz/cz/doktorandi/barrande-fellowship-program/ ). If you are interested in this option, please contact the supervisor as soon as possible.
Polymer-bound reactive oxygen species precursors for cancer therapy
Radiation therapy applies ionization radiation to cancer tissue to elicit the reactive oxygen species (ROS) production to kill the cancer cells. The radiation treatment can be boosted by application of radiosensitizers. The aim of this thesis is to prepare a polymer material that is able to deliver artificial ROS into the cancer cells or deliver precursors that will trigger the ROS generation at the place of action. Moreover, specific hypoxic markers can be utilized for active targeting to hypoxic tumor tissue. The student will design and prepare polymer systems which will be releasing ROS as: superoxide, peroxides or singlet oxygen in desired cancer site. The project is highly multidisciplinary, it includes polymer and organic syntheses, characterization techniques such as FTIR, 1-H 13-C NMR, SEC, DLS, SAXS and SANS. Moreover, the student can participate on biological studies which will be performed on collaborating workplace. If the student is interested in, it is possible to make part of the study at collaborating workplace in France within the program “double degree PhD”, the deadline is February 14, 2020 (see https://studium.ifp.cz/cz/doktorandi/barrande-fellowship-program/ ). If you are interested in this option, please contact the supervisor as soon as possible.
Polymeric drug carriers for immunooncotherapy
Immunotherapy became the highly studied type of tumor treatment, either independently or in combination with efficient chemotherapy in the last decade. Polymer drug carriers can be used for the increase of synergism of both these therapeutic approaches, and thus, to increase the tumor treatment efficiency by “immunooncotherapy”. Polymer drug carriers are non-toxic, non-immunogenic and biocompatible polymer materials enabling lower drug blood-clearance and minimization of side-effects. The doctoral project theme will consist in the development of new polymer materials suitable as drug carriers enabling controlled release of active compounds in target, i.e. tumor tissue. The polymer materials will be formed by tailor-made hydrophilic or amphiphilic copolymers. The selection of proper immunomodulation agents and the type of their linkage to the carrier will be in the spotlight. The theme is suitable for graduates of chemistry, eventually pharmacy. The student will learn new skills in the synthesis and methods of characterization and can participate in biological characterization in internal or international cooperating laboratories. We offer interesting and varied work in a well-established team of Biomedical polymers, affording hi-tech equipment and material background.
Polymeric materials for advanced applications: structure, properties and processing
Nowadays new applications and processing technologies place new and bigger demands on polymeric materials. Materials for 3D printing or electrically conductive polymer composites can serve as typical examples. In most cases these systems have a heterogeneous phase structure, which influences the end-use properties of the final material to a large extent. The aim of the work is a description of relationships between structure and properties of materials relevant for practical applications. Work activities include a preparation of polymeric materials and structural investigations by means of electron microscopy. Furthermore, mechanical and flow behaviour of prepared materials will be studied in detail.
Polymeric materials with antibacterial effects
The resistance of bacteria to antibiotics and bacterial inflammation of mucosa are serious medical problems. Investigation of materials enabling to overcome protective barriers of bacteria and their plaques or protection against their adhesion to mucosa should increase the treatment efficiency of diseases and infections caused by bacteria. In advance, biocompatible polymer materials can be used either as drug carriers overcoming biological barriers or as materials protecting against the dissemination of bacterial inflammation. The project theme will consist in the preparation and study of properties of new polymer materials suitable as carriers of antibiotics aiming to bacterial infections and related symptoms. Polymer materials will be designed as polymer carriers of antibiotics, enabling their controlled activation, or intended for the prevention of adhesion of bacteria on human mucosa. The theme is suitable for graduates of chemistry, eventually pharmacy. The student will learn new skills in the synthesis and methods of characterization and can participate in biological characterization in internal or international cooperating laboratories. We offer interesting and varied work in a well-established team of Biomedical polymers, affording hi-tech equipment and material background.
Polymeric nanomaterials for neoadjuvant multimodal therapy of advanced neoplastic diseases
The main aim of this work will be the development of new multi-component biocompatible and non-immunogenic polymer-based nanotherapeutics and nanodiagnostics adapted for multimodal advanced therapy of neoplastic diseases. The dissertation will be based on the preparation of new polymeric nanomaterials that will allow the controlled delivery of active therapeutic agents or tumor visualization for fluorescently navigated surgery. These nanomaterials will serve as a tool for multimodal neoadjuvant therapy based on sequential administration of chemotherapy and immunotherapy in combination with fluorescently navigated surgery. The work will focus on tailor-made solutions using covalent binding of active molecules with several functions: targeted transport of active molecules, their protection during transport against degradation and controlled release based on site-specific stimuli. The thesis will consist in the design, synthesis and study of physico-chemical and biological properties of polymeric materials. The applicant's knowledge and experience in organic or macromolecular chemistry is an advantage, along with the desire to learn new things in other fields, such as biochemistry. The work assumes close cooperation with cooperating biological teams in the Czech Republic and abroad.
Preparation of stimuli-responsive polymer nanomedicines using microfluidic nanoprecipitation – the in vitro and in vivo performance under simulated physiological conditions
Nanomedicines gain much more relevance in biomedical applications if they are tailored to be degradable in response to certain external stimuli. Such stimulus may be enzymatic removal of protecting groups, a pH change, light or the presence of reactive oxygen species (ROS) in cancer. Herein, imbalances on the cells micro-environment (pH changes, ROS production) will be explored for the synthesis of stimuli-responsive polymers and block copolymers. Inspired by the ease and effectiveness of the self-assembly of amphiphilic block copolymers in solution, several polymer nanomedicines, i.e., micelles, nanoparticles and vesicles will be designed to display tunable stimuli degradation in the presence of physiologically relevant changes in pH, temperature or ROS concentrations and will be prepared by microfluidic nanoprecipitation. This technique allows us the production of uniform particles with controllable size, shape and surface chemistry in a reproducible manner. The produced polymer self-assemblies will be characterized using standard scattering techniques (DSL/SLS/ELS, SAXS and SANS) and by microscopy. The effectiveness of the polymer nanosystems will be evaluated in in vitro and in in vivo models simulating the physiological balanced and imbalanced of the microenvironment.
Radiation resistant polymers for dosimetry and space applications
The aim of the project is the preparation and testing of radiation-resistant organic polymers usable in water or cosmic environment. The key property of polymers resistant to ionizing and UV radiation is their ability to eliminate free radicals which are created by interactions of radiation with chemical substances. Degradation effects caused by free radicals are usually reduced by addition of low-molecular antidegradants physically admixed into the polymer matrix. The objective of the dissertation is an improvement of polymer matrixes with polymer antidegradants bearing functional groups on macromolecular chains, which enhances their ability to remain in the matrix and protect the polymer for long time (in water or vacuum). The work will be focused on preparation and testing of the stabilized polymer materials by physicochemical methods and examining possibilities of their practical use. The topic will be investigated in collaboration with an industrial partner aiming at: 1) production of polymer protective packaging for a new type of clinical dosimeters for measurement; 2) development of polymer materials with sustained light transmittance stability that can be used as external protection of photovoltaic panels on satellite systems.
Selective polymer therapeutics for eradication of cancer stem cells and monitoring therapeutic efficacy using exosomes
Polymeric drug carriers allow targeting of drugs to the target site, and also minimize the side effects of therapy. Tumor stem cells (TSC) remain resistant to conventional and also polymeric drugs therapy and are often at the origin of metastasis. Tumor eradication and targeted TSC is one of the unresolved topics of tumor therapy. Exosomes have been extensively studied to monitor the modulation of the body's response to antitumor therapy and the development of metastases. Vesicles derived from the plasma membrane of cells are important indicators of physiological and pathological processes and at the same time they can transport drugs. The aim of the project will be preparation of polymer therapeutics, selection of TSC and study of cellular response to interaction with polymer carriers and drugs, resp. intercellular communication via microparticles and exosomes, their characterization and modulation of their formation depending on the type of carrier and drug. The proposed topic concerns the overlap of the fields of biochemistry, macromolecular chemistry and molecular biology, which is currently very current with regard to the necessary interconnection of disciplines leading to more effective drug development and therapeutic approaches. In addition to the basic techniques necessary for the preparation of macromolecules, the student will learn basic methods of cell and molecular biology.
Self-assembled multiresponsive polymer systems for biomedical use
Self-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 will be designed for diagnostics and personalized therapy of cancer and infectious diseases. Optimized nanoparticles will be then provided to collaborating biological workplaces for in vivo testing. If the student is interested in, it is possible to make part of the study at collaborating workplace in France within the program “double degree PhD”, the deadline is February 14, 2020 (see https://studium.ifp.cz/cz/doktorandi/barrande-fellowship-program/ ). If you are interested in this option, please contact the supervisor as soon as possible.
Self-cleaning anti-biofilm polymer surfaces
The 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 anti-biofilm 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.
Study on polymer-bound immunomodulators for medical purposes
Biocompatible and biodegradable polymer based molecules are very interesting and nowadays widely studied materials. Their structure and characteristics are suitable for binding a number of molecules, e.g. therapeutics, inhibitors or stimulants. This polymer-bound therapeutics show less side effects than free drug and provide the possibility of better targeting of tissues and cells. The immune system of animals, including human, is a complex of cellular structures, individual cells and biochemical reactions. It’s the line of one’s first defense in infectious and non-infectious diseases. This dissertation will include the design of polymer structures, selection of suitable effector ligands, chemical synthesis and testing of molecules in vitro on cell and bacterial lines and on blood samples donated from donors or patients. This dissertation is an intersection of macromolecular chemistry, biochemistry, cellular and molecular biology and microbiology. All data and information acquired during this research will be used for further development of molecules able to modulate immune response according to the therapy of choice.
Synthesis of polymeric drugs for chemoresistant tumors
Chemotherapy is an important modality in treatment of malignant diseases, however, it is seriously limited by chemo-resistance of many tumors. The main goal of the dissertation is to design structures, synthesis and study of physicochemical and biological properties of bio-degradable polymeric conjugates of anticancer drugs and STAT3 inhibitors. These conjugates should be able to suppress the side effects of conventional chemotherapy and also avoid tumor chemorezistence. Polymeric HPMA-based carriers will be prepared by new controlled polymerization methods, especially RAFT or CuRDRP. Synthetized will be carriers with linear, diblock or differently branched structure. The focus will be on organic and polymer synthesis of new polymeric conjugates and their characterization using modern instrumental techniques (SEC, FFFF, LC-MS, NMR, etc.). Testing of prepared drugs in biological systems will be done in cooperation with domestic and foreign partners. The knowledge and experience of an applicant in organic and / or macromolecular chemistry is an advantage, along with the desire to learn new things in other fields such as biochemistry or biology. We offer interesting and varied work in a young dynamic team at a top-quality academic workplace.