Laboratory of Experimental Medicine

The Laboratory of Experimental Medicine (LEM) was established in 1998 at the Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital in Olomouc. Later in 2010, the LEM became a moving force in building-up and establishment of the Institute of Molecular and Translational Medicine.

Our researchers are organized to research groups and perform molecular, cellular and integrative research at the highest international level and to train a new generation of successful scientists. We study biological processes that govern normal and pathological human bodily functions that are involved in disease pathogenesis. Albeit our research is disease agnostic, most of our expertise relates to cancer, inflammation, infection, rare diseases and neurodegeneration. Our spectrum of research ranges from basic and translational science, including research and development of small molecules, radiopharmaceutics, identification of new therapeutic targets, drug repurposing, first use of molecules in man (Phase I trials), biomarker identification and validation trials, development of in vitro diagnostics, through to real-world evidence studies using routinely collected data.Several of our research environments have been recognized as outstanding both at the national and European levels. We also strive to stimulate our young researchers with our enthusiasm for research and wish to increase their interest in both basic and applied sciences. We expose them to the most up-to-date science, cutting edge technologies and prepare them for lifelong learning in their future careers.

Research interests

Our research interests and domains include

Research and development of small molecules and biologics for innovative therapies
Imaging and tracing of human diseases, development of radiopharmaceutics
Identification and validation diagnostic, prognostic and predictive biomarkers to advance early disease diagnostics and personalized medicine
Better understanding disease complexity employing multidimensional -omic techniques (proteomics, genomics, transcriptomics, metabolomics, lipidomics, cellulomics, etc.)
Advancing high-throughput biology and screening techniques in medical research
Research on translational in vitro and in vivo models (e.g. organoids, patient-derived xenografts, induced pluripotent stem cells)
Development of information technologies, including the artificial intelligence, and solutions to support data stewardship in biomedical domain
Advancing nanotechnologies for treatment and detection of human disorders; Proof-of-concept preclinical and early clinical trials.

Journals

KOTULOVÁ, J., M. HAJDÚCH, P. DŽUBÁK

Current Adenosinergic Therapies: What Do Cancer Cells Stand to Gain and Lose?. International Journal of Molecular Sciences. 2021, 22(22), 12569, ISSN: 1422-0067, PMID: 34830449, PDF.

RAFFAELE, M., K. KOVACOVICOVA, T. BIAGINI, O. LO RE, J. FROHLICH, S. GIALLONGO, J. NHAN, A. GIANNONE, D. CABIBI, M. IVANOV, A. TONCHEV, M. MISTRÍK, M. LACEY, P. DŽUBÁK, S. GURSKÁ, M. HAJDÚCH, J. BÁRTEK, T. MAZZA, V. MICALE, S. CURRAN, M. VINCIGUERRA

Nociceptin/orphanin FQ opioid receptor (NOP) selective ligand MCOPPB links anxiolytic and senolytic effects. Geroscience. 2021, 44(1), 463-483, ISSN: 2509-2715, PMID: 34820764,

LIGASOVÁ, A., I. ROSENBERG, M. BOCKOVA, J. HOMOLA, K. KOBERNA

Anchored linear oligonucleotides: the effective tool for the real-time measurement of uracil DNA glycosylase activity. Open Biology. 2021, 11(10), 200136, ISSN: 2046-2441, PMID: 34665968, PDF.

Open positions

Projekt:	Postdoctoral fellow/Researcher
Vedoucí:	Polishchuk Pavlo Ph.D., M.Sc.
K dispozici:	1
Určeno pro:	Postdoktorandské studium
Souhrn:	The group of chemoinformatics and drug design at the Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc, Czech Republic (https://imtm.cz/laboratories/chemoinformatics-and-drug-design) seeks for a postdoctoral fellow with experience in chemoinformatics and programming. The primary objective of the group is development of new computational approaches and software tools in drug design and their application in medicinal chemistry projects on hit/lead identification/optimization and target identification. The successful candidate will be mainly involved into the project on de novo fragment-based drug design and optimization. He/she will implement new and improve existing tools and approaches, validate them retrospectively and apply those tools in ongoing medicinal chemistry projects conducting at our institution in close collaboration with medicinal chemists and biologists. The candidate can be involved in other research projects depending on his/her experience and skills. The formal requirements: PhD in chemistry, chemoinformatics, computer science or related fields or 3 years of experience in relevant fields experience with molecular docking/pharmacophore modeling/machine learning knowledge of RDKit good Python programming skills and experience in software development data analysis skills basic medicinal chemistry knowledge is a plus good publication record excellent writing and spoken English The position will be opened for 2-3 years with a possibility of extension. Informal inquiries as well as applications, including curriculum vitae and bibliography, cover letter describing candidate research interests and past accomplishments should be sent via email to pavlo.polishchuk@upol.cz.

Projekt:	Systems approaches to understanding aging and neurodegeneration
Vedoucí:	Das Viswanath M.Sc., Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium

Projekt:	Role of axonal transport and pathology in neurodegeneration
Vedoucí:	Das Viswanath M.Sc., Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium

Projekt:	New chemoinformatics approaches to fragment-based drug discovery
Vedoucí:	Polishchuk Pavlo Ph.D., M.Sc.
K dispozici:	1
Určeno pro:	Doktorské studium

Projekt:	Research and development of agents for cancer, neurodegenerative and infectious diseases
Vedoucí:	De Sanctis Juan Bautista Ph.D., Hajdúch Marián M.D., Ph.D., Džubák Petr M.D., Ph.D., Urban Milan Ph.D., Das Viswanath M.Sc., Ph.D.
K dispozici:	5
Určeno pro:	Doktorské studium

Projekt:	New methods in protein degradation
Vedoucí:	Holub Dušan Ph.D., Hajdúch Marián M.D., Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium

Projekt:	Isolation and analysis of membrane lipid rafts using a non-targeted metabolomics and lipidomics approach
Vedoucí:	Najdekr Lukáš Ph.D.
K dispozici:	1
Určeno pro:	Doktorské studium

Projekt:	Use of open-source software approaches for analysis of metabolomic and lipidomic clinical data
Vedoucí:	Najdekr Lukáš Ph.D.
K dispozici:	1
Určeno pro:	Doktorské studium

Projekt:	Search and study of the mechanism of action of substances affecting the viability and motility of human spermatozoa
Vedoucí:	Voller Jiří Ph.D.
K dispozici:	1
Určeno pro:	Doktorské studium

Projekt:	Search and study of the mechanism of action of new circadian rhythm modulators for the therapy of civilization diseases
Vedoucí:	Voller Jiří Ph.D.
K dispozici:	1
Určeno pro:	Doktorské studium

Projekt:	Study of basic pharmacokinetic properties (ADME) of new drugs in preclinical development
Vedoucí:	Lišková Barbora Ph.D.
K dispozici:	1
Určeno pro:	Doktorské studium

Projekt:	Identification of proteomic biomarkers in proximal fluids and tissues
Vedoucí:	Džubák Petr M.D., Ph.D., Hajdúch Marián M.D., Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium

Projekt:	Preclinical development of molecular imaging agents
Vedoucí:	Petřík Miloš Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium

Projekt:	Plasmonic nanomaterials in cancer theranostics
Vedoucí:	Ranc Václav Ph.D., Petřík Miloš Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium

Projekt:	Synthesis and characterization of 2D nanoplatforms as active drug carriers
Vedoucí:	Ranc Václav Ph.D., Hajdúch Marián M.D., Ph.D.
K dispozici:	3
Určeno pro:	Doktorské studium

Projekt:	Liquid biopsies in experimental and clinical oncology
Vedoucí:	Srovnal Josef M.D., Ph.D., Koudeláková Vladimíra Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium

Projekt:	Ligand- and structure-based modeling of biologically active compounds
Vedoucí:	Polishchuk Pavlo Ph.D., M.Sc.
K dispozici:	1
Určeno pro:	Doktorské studium

Projekt:	Multimodal imaging methods for preclinical testing of new bioactive molecules
Vedoucí:	Nový Zbyněk Ph.D., Petřík Miloš Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium

Projekt:	Diagnosis and treatment of rare diseases
Vedoucí:	Hajdúch Marián M.D., Ph.D., Srovnal Josef M.D., Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium

Projekt:	Modifications of biologically active molecules leading to improvement of their pharmacological properties
Vedoucí:	Urban Milan Ph.D., Ranc Václav Ph.D., Polishchuk Pavlo Ph.D., M.Sc.
K dispozici:	3
Určeno pro:	Doktorské studium

Projekt:	Biologically active molecules and their therapeutic combinations
Vedoucí:	Hajdúch Marián M.D., Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium

Projekt:	Physiology and pathophysiology of ageing
Vedoucí:	Hajdúch Marián M.D., Ph.D., Voller Jiří Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium

Projekt:	Search and characterization of compounds for the therapy of congenital or acquired diseases caused by aberrant pre-mRNA editing
Vedoucí:	Voller Jiří Ph.D.
K dispozici:	1
Určeno pro:	Doktorské studium

Projekt:	Bioinformatics processing of big data in clinical and preclinical studies
Vedoucí:	Hajdúch Marián M.D., Ph.D., Pavliš Petr Ph.D., Vrbková Jana Ph.D.
K dispozici:	3
Určeno pro:	Doktorské studium

Projekt:	Anticancer drugs targeting nucleic acid metabolism
Vedoucí:	Hajdúch Marián M.D., Ph.D., Džubák Petr M.D., Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium

Projekt:	Identification of proteomic biomarkers in exhaled breath condensate patients with systemic or pulmonary disease
Vedoucí:	Džubák Petr M.D., Ph.D., Hajdúch Marián M.D., Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium

Projekt:	Development of 3D pharmacophore signatures and their application in anticancer drug design
Vedoucí:	Polishchuk Pavlo Ph.D., M.Sc.
K dispozici:	1
Určeno pro:	Doktorské studium

Projekt:	Identification of molecular targets and resistance mechanisms of anticancer drugs by cell biology and proteomics methods
Vedoucí:	Hajdúch Marián M.D., Ph.D., Džubák Petr M.D., Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium

Projekt:	Genetic and epigenetic biomarkers in health and disease
Vedoucí:	Slavkovský Rastislav Ph.D., Džubák Petr M.D., Ph.D., Hajdúch Marián M.D., Ph.D., Drábek Jiří Ph.D., Koudeláková Vladimíra Ph.D.
K dispozici:	5
Určeno pro:	Doktorské studium

Projekt:	New prognostic and predictive factors in solid tumors
Vedoucí:	Hajdúch Marián M.D., Ph.D., Srovnal Josef M.D., Ph.D., Koudeláková Vladimíra Ph.D.
K dispozici:	3
Určeno pro:	Doktorské studium

Projekt:	Diagnostics and therapy of rare diseases
Vedoucí:	Hajdúch Marián M.D., Ph.D., Srovnal Josef M.D., Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium
Souhrn:	2 places in full-time study

Projekt:	Drug development of small molecules
Vedoucí:	Hajdúch Marián M.D., Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium
Souhrn:	2 places in full-time study

Projekt:	Drug repurposing for treatment and prevention of diseases
Vedoucí:	Hajdúch Marián M.D., Ph.D.
K dispozici:	1
Určeno pro:	Doktorské studium
Souhrn:	1 place in full-time study

Projekt:	Physiology and pathophysiology of aging
Vedoucí:	Hajdúch Marián M.D., Ph.D., Voller Jiří Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium
Souhrn:	2 places in full-time study

Projekt:	Identification of molecular targets and mechanisms of resistance in antitumor drugs using cell biology and proteomics methods
Vedoucí:	Džubák Petr M.D., Ph.D., Hajdúch Marián M.D., Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium
Souhrn:	2 places in full-time study

Projekt:	Search and characterization of substances for the therapy of congenital or acquired diseases caused by aberrant splicing of pre-mRNA
Vedoucí:	Voller Jiří Ph.D.
K dispozici:	1
Určeno pro:	Doktorské studium
Souhrn:	1 place in full-time study

Projekt:	Genetic and epigenetic biomarkers of cancer diseases
Vedoucí:	Drábek Jiří Ph.D.
K dispozici:	1
Určeno pro:	Doktorské studium
Souhrn:	1 place in full-time study

Projekt:	Bioinformatics processing of big data within clinical and preclinical studies
Vedoucí:	Hajdúch Marián M.D., Ph.D., Pavliš Petr Ph.D.
K dispozici:	3
Určeno pro:	Doktorské studium
Souhrn:	3 places in full-time or combined form of study

Projekt:	Antitumor drugs targeting nucleic acid metabolism
Vedoucí:	Džubák Petr M.D., Ph.D., Hajdúch Marián M.D., Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium
Souhrn:	2 places in full-time study

Projekt:	Identification of proteomic biomarkers in exhaled air condensate in patients with systemic or pulmonary disease
Vedoucí:	Džubák Petr M.D., Ph.D., Hajdúch Marián M.D., Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium
Souhrn:	2 places in full-time study

Projekt:	The role of tumor hypoxia in the development of acquired resistance to microtubule-targeted drugs
Vedoucí:	Das Viswanath M.Sc., Ph.D.
K dispozici:	1
Určeno pro:	Doktorské studium
Souhrn:	1 place in full-time study

Projekt:	Development of 3D pharmacophore signatures and their application in the design of anticancer drugs
Vedoucí:	Polishchuk Pavlo Ph.D., M.Sc.
K dispozici:	1
Určeno pro:	Doktorské studium
Souhrn:	1 place in the face-to-face form of study

Projekt:	Genetic and epigenetic biomarkers of cancer diseases
Vedoucí:	Slavkovský Rastislav Ph.D., Džubák Petr M.D., Ph.D., Hajdúch Marián M.D., Ph.D.
K dispozici:	3
Určeno pro:	Doktorské studium
Souhrn:	3 places in full-time study

Projekt:	New prognostic and predictive factors in solid tumors
Vedoucí:	Hajdúch Marián M.D., Ph.D., Srovnal Josef M.D., Ph.D.
K dispozici:	3
Určeno pro:	Doktorské studium
Souhrn:	3 places in full-time or combined form of study

Projekt:	Applicability domains in machine learning modeling
Vedoucí:	Polishchuk Pavlo Ph.D., M.Sc.
K dispozici:	1
Určeno pro:	Magisterské studium

Projekt:	Computationally guided optimization of compound properties
Vedoucí:	Polishchuk Pavlo Ph.D., M.Sc.
K dispozici:	1
Určeno pro:	Magisterské studium

Projekt:	Novel 3D pharmacophore representation for machine learning
Vedoucí:	Polishchuk Pavlo Ph.D., M.Sc.
K dispozici:	1
Určeno pro:	Magisterské studium

Projekt:	Fragment-based de novo design using pharmacophore models
Vedoucí:	Polishchuk Pavlo Ph.D., M.Sc.
K dispozici:	1
Určeno pro:	Magisterské studium

Projekt:	Radiolabelled peptides for cancer imaging
Vedoucí:	Petřík Miloš Ph.D.
K dispozici:	1
Určeno pro:	Magisterské studium

Projekt:	Radiolabelled siderophores for infection imaging
Vedoucí:	Petřík Miloš Ph.D.
K dispozici:	1
Určeno pro:	Magisterské studium

Projekt:	In vivo imaging of 68Ga labelled biomolecules
Vedoucí:	Petřík Miloš Ph.D.
K dispozici:	1
Určeno pro:	Bakalářské studium

Projekt:	Small animal imaging using microPET/SPECT/CT system in preclinical developement of potential drugs
Vedoucí:	Nový Zbyněk Ph.D.
K dispozici:	1
Určeno pro:	Bakalářské studium

Projekt:	Biochemical and cellular analysis of amyloid staining agents in models of tauopathies and synucleopathies
Vedoucí:	Das Viswanath M.Sc., Ph.D.
K dispozici:	2
Určeno pro:	Bakalářské studium

Projekt:	Development of organoid assays for anti-tumour drug screening
Vedoucí:	Das Viswanath M.Sc., Ph.D.
K dispozici:	2
Určeno pro:	Bakalářské studium

Projekt:	Drug synergy studies in 3D spheroids cultures of tumour cell lines
Vedoucí:	Das Viswanath M.Sc., Ph.D.
K dispozici:	2
Určeno pro:	Bakalářské studium

Projekt:	Epigenetic biomarkers
Vedoucí:	Drábek Jiří Ph.D.
K dispozici:	1
Určeno pro:	Magisterské studium

Projekt:	Genetic biomarkers
Vedoucí:	Drábek Jiří Ph.D.
K dispozici:	1
Určeno pro:	Magisterské studium

Projekt:	In silico design of compounds with desired properties
Vedoucí:	Polishchuk Pavlo Ph.D., M.Sc.
K dispozici:	2
Určeno pro:	Doktorské studium
Souhrn:	One of the main goals of chemoinformatics is development of new compounds with desired properties or activities. Many de novo design approaches were suggested so far. The designed compounds should satisfy multiple criteria, e.g. synthetic accessibility, novelty, diversity, selectivity, etc. Generators of chemical structures satisfying these criteria are a core of all de novo design approaches. Available approaches often result in synthetically hardly accessible structures or limit their diversity and novelty. Within this study a new fragment-based approach for structure generation will be implemented which will result in chemically valid structures and will provide flexible control over their diversity, novelty and synthetic accessibility. This will be used for development of de novo design approaches based on molecular docking, pharmacophore modeling to generate compounds which will be able to fit to a binding site of a given protein. This can be used for development of novel compounds and for optimization of structures of available ligands. Developed approaches should be implemented in open-source software tools.

Projekt:	Development of 3D pharmacophore signatures and their applications to drug design
Vedoucí:	Polishchuk Pavlo Ph.D., M.Sc.
K dispozici:	1
Určeno pro:	Doktorské studium
Souhrn:	Pharmacophore modeling is a powerful approach to encode possible protein-ligand interactions and searching of new promising compounds in large libraries. So far, almost all available software for pharmacophore modeling is proprietary and implemented approaches have some limitations to efficiently work with big data. Within this study a new approach to represent 3D pharmacophores as hashes will be implemented. This representation will make it possible to quickly identify similar pharmacophores in large data sets. This property can be used to develop a new alignment free approach to ligand-based pharmacophore modeling. The developed 3D pharmacophore hashes will help to identify representative pharmacophores retrieved from molecular dynamic simulation of protein-ligand complexes. These developments will increase success rates of future screening campaigns and should be implemented in open-source software.

Projekt:	Bio- and cheminformatics in biology of aging
Vedoucí:	Voller Jiří Ph.D.
K dispozici:	1
Určeno pro:	Doktorské studium
Souhrn:	Although hundreds of biological databases are available, a richly annotated database of anti-aging compounds with diverse mechanisms of action has been missing. The aim of the project is to create a database of compounds with anti-aging activity that would offer a rich annotation of both compound and involved biological mechanisms. The data will be collected from a wide range of public databases, by text-mining of scientific literature and patents as well as from results of in-house high-throughput screening. The data will be used for formulation of new hypotheses of mechanisms of aging as well as for identification of novel anti-aging compounds.

Projekt:	Pharmacokinetic methods in preclinical drug testing
Vedoucí:	Hajdúch Marián M.D., Ph.D., Lišková Barbora Ph.D.
K dispozici:	1
Určeno pro:	Doktorské studium
Souhrn:	The study of ADME properties of a potential drug that are part of the IMTM chemical library - obtained by national or international cooperation belongs to one of the first steps in predicting potential drugs. In vitro models generate many ADME parameters, including chemical, plasma and microsomal stability, plasma protein binding and proportion of passive diffusion as a transport mechanism. The Caco-2 and MDCK-MDR1 permeability assays are established models of intestinal and blood-brain barriers, respectively. Analysis of samples is performed using a Agilent RapidFire 300 - rapid online solid phase extraction with subsequent detection of the mass spectrometer Qtrap 5500 (AB Sciex) - RF/MS. High-Throughput Mass Spectrometry System RF/MS delivers ultrafast, label – free analysis of native compounds for biochemical assays in ADME and provide throughput speeds of 6 to 10 seconds per sample.

Projekt:	Multimodal imaging methods for testing bioactive molecules in vivo
Vedoucí:	Petřík Miloš Ph.D., Nový Zbyněk Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium
Souhrn:	The student will employ modern in vivo imaging techniques namely positron emission tomography, single-photon emission tomography, computed tomography and optical imaging in order to elucidate effect of novel anticancer or antimicrobial agents. The other part of the project will be assessment of novel radiotracers directed towards targets expressed by tumour cells or by microbial pathogens. Daily work routine will include all proper working steps common in radiopharmacy, i.e. starting with gaining an radioisotope from dedicated source, radiolabelling of selected compound, quality control (HPLC/TLC), stability tests, in vitro testing of biological properties and finally in vivo procedures (biodistribution, static/dynamic imaging). Expected previous education includes medicine, pharmacy, pharmacology or related field.

Projekt:	A combination of 2D and 3D cell cultures for a smart and effective identification and characterization of anti-hypoxic candidates
Vedoucí:	Das Viswanath M.Sc., Ph.D.
K dispozici:	1
Určeno pro:	Doktorské studium
Souhrn:	Hypoxia is a prominent feature of different solid tumor types. A central component of hypoxic adaptation is the stabilization of hypoxia-inducible factor-1 (HIF-1), a key transcriptional regulator of hypoxia that orchestrates the transcriptional regulation of genes involved in a plethora of cellular processes. Considering the multiple roles of HIF-1 in cancer, interest in novel small-molecule inhibitors of the HIF-1 pathway has steadily increased over the past 10 years. However, despite extensive research, no specific inhibitor of HIF-1 has been brought to the market, making the field still ripe for further exploration. The goal of the present work is to utilize the potential of a combination of 2D and 3D cellular models for identification and characterization of inhibitors of HIF-1 and/or HIF-1 pathway by screening in 2D cultures, and lightsheet microscopy and mass spectrometry studies in spheroid cultures.

Projekt:	Screening and characterization of compounds for therapy of diseases caused by aberrant pre-mRNA splicing
Vedoucí:	Voller Jiří Ph.D.
K dispozici:	1
Určeno pro:	Doktorské studium
Souhrn:	Recently, we identified several novel modulators of alternative splicing with the ability to increase expression of wild-type transcripts of several genes relevant for neurodegeneration or cancer. However, mechanisms of action of those promising compounds remains unclear. The aim of the project is to (i) identify molecular targets and relevant pathways, (ii) design assays for high-througput screening of a library of chemical compounds, and (iii) to identify novel structural types of active compounds.

Projekt:	Screening and characterization of compounds for therapy of mitochondrial and metabolic disorders
Vedoucí:	Voller Jiří Ph.D.
K dispozici:	1
Určeno pro:	Doktorské studium
Souhrn:	Pharmacotherapy of hereditary mitochondrial diseases including neurodegenerations and cardiopathies is only symptomatical at present. The aim of this study is to identify the novel candidate drugs by high-throughput screening using patient-derived cell lines. The assays will evaluate survival under metabolic and oxidative stress as well as morphology and function of mitochondria. Mechanism of action of promising compounds will be studied by OMICS methods.

Projekt:	Drug resistance mechanisms in cancer
Vedoucí:	Džubák Petr M.D., Ph.D., Hajdúch Marián M.D., Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium
Souhrn:	Mechanisms of tumor cell resistance to newly developed and existing nucleoside analog cytostatics will be studied. These drugs are used in most anti-cancer therapy protocols and the emergence of drug resistance is a major problem in the treatment of cancer patients. Resistant cell lines prepared in the past will be studied to identify the key mechanisms of resistance, which will be carried out by their detailed characterization using cell biology, but also proteomics and molecular genetics. The significance of the identified changes will be further verified on clinical material and will be applied in the development of new anticancer drugs from this class.

Projekt:	The role of tumor hypoxia in the acquisition of resistance to microtubule-targeting drugs
Vedoucí:	Das Viswanath M.Sc., Ph.D.
K dispozici:	1
Určeno pro:	Doktorské studium
Souhrn:	Hypoxia is one of the major factors causing resistance to microtubule-stabilizing drugs (MSDs) and other non-microtubule drugs used in chemotherapy. Hypoxia results in changes in tubulin conformation, expression of tubulin isotypes and metabolic pathways that make cancer cells less susceptible to paclitaxel, a taxane used extensively in the treatment of solid tumors. Recent cellular studies have shown that non-taxane MSDs with a similar mode of microtubule stabilization to paclitaxel is more effective in hypoxic cancer cells than paclitaxel. Due to a different microtubule-binding site, we hypothesize that non-taxane MSDs may have a better cytotoxic effect in cancer cells under hypoxia. The goal of this project is to study the anti-cancer effect of non-taxane MSDs in hypoxic ovarian and cervical cancer cell models.

Projekt:	Identification of molecular targets of anticancer therapy applying cell biology and proteomics tools
Vedoucí:	Džubák Petr M.D., Ph.D., Hajdúch Marián M.D., Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium
Souhrn:	Selected, highly active derivatives of triterpenes, chelators and nucleosides will be studied with a view to identify the mechanisms of their antitumor effects. Advanced methods of cell biology, proteomics and genomics such as affinity purification of protein targets, CETSA and others will be used for their study. The identified targets will be validated in relation to their clinical relevance in anticancer therapy.

Projekt:	Pathological conditions associated with human papillomavirus infection
Vedoucí:	Koudeláková Vladimíra Ph.D., Hajdúch Marián M.D., Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium
Souhrn:	High-risk human papillomavirus infection (HPV infection) is associated with several cancers such as cervical, vaginal, vulvar, head and neck, anal, and penile carcinomas. Nearly all cervical cancers are caused by HPV infection. Despite available vaccination and cervical cancer screening program, cervical cancer is one of the most common types of cancer affecting women worldwide. Main problems of cervical cancer screening are low participation rate and low sensitivity of cytology which is still used in the majority of cervical cancer screening programs. Solution could be the transition to primary HPV screening and the sending of self-sampling devices to cervical cancer screening non-attenders. The best strategy for enrolling Czech women in the screening program will be analysed during this project. Obtained samples will be tested for the presence of HPV DNA and the presence of other molecular biomarkers important in viral clearance and cervical cancer progression/regression. Discoveries will lead to identification of biomarkers for early diagnosis, disease progression or triage strategies. The aim of the project is to clarify the best strategy for enrolling women who do not attend cervical cancer screening program. The second aim is to study genetic and proteomic profile of HPV positive/negative women with normal/abnormal cervical cytology as well as genetic variants of HPV and its importance for regression/progression of the disease. Skills to be taught include biochemistry, molecular biology, bioinformatics and cell culture. This is an ideal project for a student who wishes to pursue higher studies in cancer research. The project will use various techniques including PCR, in situ hybridization, next generation sequencing, mass spectrometry.

Projekt:	An extensive structural and biochemical characterization of tau oligomeric species in Alzheimer’s disease and other tauopathies
Vedoucí:	Das Viswanath M.Sc., Ph.D.
K dispozici:	1
Určeno pro:	Doktorské studium
Souhrn:	An extensive structural and biochemical characterization of tau oligomeric species in Alzheimer’s disease and other tauopathies

Projekt:	Identification of pro-longevity pathways and mechanisms of model organisms
Vedoucí:	Voller Jiří Ph.D.
K dispozici:	1
Určeno pro:	Doktorské studium
Souhrn:	The aim of the project is to identify the novel compounds which can increase life-span of C. elegans, increase their resistance against stress and neurodegeneration, using high-throughput and high-content screening platforms. Active compounds will be further studied in human cell cultures. Mechanisms of action of interesting hits will be studied by OMICS

Projekt:	Biology of aging and DNA damage
Vedoucí:	Hajdúch Marián M.D., Ph.D.
K dispozici:	1
Určeno pro:	Doktorské studium

Projekt:	Identification of proteomic biomarkers in exhaled breath condensate in patients with systemic or pulmonary disease
Vedoucí:	Džubák Petr M.D., Ph.D., Hajdúch Marián M.D., Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium
Souhrn:	Ph.D. topic is focused on the identification of biomarkers of lung diseases by means of a non-invasive collection of exhaled breath condensate. The project will monitor the presence of proteins in exhaled air in various diseases such as asthma, cystic fibrosis, lung tumors, or some infectious diseases, as well as quantitative changes of these proteins compared to a healthy population. Changes in these potential biomarkers with respect to therapeutic response and disease progression will be evaluated and validated.

Projekt:	Genetic and epigenetic biomarkers in cancer
Vedoucí:	Drábek Jiří Ph.D., Slavkovský Rastislav Ph.D., Hajdúch Marián M.D., Ph.D.
K dispozici:	3
Určeno pro:	Doktorské studium
Souhrn:	Clonal hematopoiesis of indeterminate potential (CHIP) has recently been described as a common phenomenon associated with aging. It is characterized by the accumulation of somatic mutations in cells of the hematopoietic system. Although CHIP is manifested by the expansion of certain cell clones, this condition is not accompanied by any morphological features of hematological neoplasia. However, it has been shown that the incidence of clonal hematopoiesis correlates with increased overall mortality and the risk of developing malignant transformation of hematopoietic cells as well as cardiovascular disease, such as ischemic stroke. To what extent and by what mechanisms clonal hematopoiesis contributes to disease development remains a question of current research. The main aim of the project will be to pinpoint the principal cells carrying CHIP somatic mutations, and to study their role in development and maintenance of atherosclerotic plaques, especially of those involved in development of stroke. The comparison of the phenotype of CHIP positive and negative cells will be of special interest. The use of cellular models not only include different types of leucocytes but circulatory progenitor endothelial cells as well. The study will involve elderly subjects with the positive presence of CHIP (>65 years). Subject will be characterized based on the presence or absence of ischemic stroke and the presence or absence of carotid stenosis by our clinical collaborators. The presence of somatic variants in 38 selected genes associated with CHIP will be tested in subjects of interest within our research group. The project will use various techiques including FACS, MACS, cell cultures, DNA isolation from small amount of cells, a highly sensitive sequencing method for DNA genotyping allowing detection of variant with less than 1% allelic frequency, DNA/RNA sequencing library preparation, deep massively parallel sequencing of panel of genes using unique molecular barcodes/indices, RNAseq, bioinformatics and data analysis with possibilities of calculations using high performance computing cluster, data management and statistical evaluation.

Projekt:	New prognostic and predictive factors in solid tumors
Vedoucí:	Srovnal Josef M.D., Ph.D., Hajdúch Marián M.D., Ph.D.
K dispozici:	2
Určeno pro:	Doktorské studium
Souhrn:	Cancer is the second leading cause of death in the western countries. Early diagnosis and targeted therapy improve the therapeutic outcome. With the emergence of new biotechnologies, diagnosis can be made early and precisely, and the knowledge of tumor molecular genetics can identify the most appropriate therapy for a particular patient. The sensitivity of modern molecular methods makes it possible to characterize the tumor properties from sites remote from the primary tumor using patient's blood. The subject of the offered study program is the identification of new prognostic and predictive biomarkers of cancer using liquid biopsies. This is particularly the analysis of circulating tumor cells (CTCs), circulating free tumor DNA (ctDNA) and circulating miRNAs. The aim of the project is to further implement a liquid biopsy concept into the diagnosis and therapy monitoring of solid tumors, especially colorectal, breast, lung and CNS tumors. These include therapy response and resistance monitoring, identifying new therapeutic targets and estimating disease prognosis. The project will provide training in widely-used, transferable techniques, including circulation tumor cells capture system, digital droplet PCR, reverse-transcription qPCR, RNA-seq, single cell analyses, xenografts models and other multi-omics methods. We are looking for candidates with a background in Molecular Biology, Medicine, Cell Biology or a related area, who are enthusiastic about investigating novel approaches in cancer diagnostic that have significant potential for public health.