PhD Programme

PhD Programme

RNDr. Ladislav Anděra, CSc.

RNDr. Ladislav Anděra, CSc.

About us

PhD program BIOCEV is an integral part of post-gradual study in biotechnology and biomedicine comprising within the BIOCEV centre research groups from the Charles University - Faculty of Science and 1st Faculty of medicine and the Czech Academy of Sciences (CAS) - Institute of Biotechnology and groups from five other institutes - Institute of Molecular Genetics, Institute of Microbiology, Institute of Physiology, Institute of Experimental Medicine, and Institute of Macromolecular Chemistry.

Individual PhD study programs are organized by relevant postgraduate study boards, their members are well-known researchers and teachers from both Charles University and CAS. The research focus of the BIOCEV centre encompasses functional genomics, cell biology and virology, structural biology and protein engineering, biomaterials and tissue engineering, as well as on new therapies.

Currently at the BIOCEV centre resides 56 research groups, which are supported by 6 specialized infrastructures and service laboratories (phenogenomics, genomics and proteomics, fluorescence and electron microscopy, flow cytometry, quantitative and digital PCR, protein and nucleic acids crystallization, various diffraction techniques and mass spectroscopy.

Researchers at the BIOCEV centre within their research projects supervise PhD students and participate in the education of bachelor and magister students. Within the individual research groups, students supervised by experienced researchers or specialists, learn various experimental techniques and methodical approaches essential for successful study and defense of their MSc or PhD Theses.

At the present over 300 students participate in various research projects at the BIOCEV centre. The major goal of postgraduate study at BIOCEV encompasses both gaining new and detail knowledge in chosen research field as well as mastering various laboratory skills and techniques, rational planning, running and critical evaluation of research experiments. Last but not least the postgraduate students at BIOCEV are being involved in manuscripts preparation, apply for their own student research projects and learn how to present their scientific discoveries.

Download our PhD poster (A4) HERE or Banner HERE

News

Open PhD Projects

The open position/projects for PhD study in the research laboratories at BIOCEV for the academic year 2021/2022 are listed below with links to additional information about these PhD project. For those who would be interested in any of the listed projects please fill-in and submit the attached application form with the optional selection of up to three PhD projects (please read GDRP – bottom right link).

PhD Project Project Leader Laboratory

The project will address the role of mitochondrial function and metabolism and its impact on cancer resistance. It is clear that these organelles are vital in the process of carcinogenesis, but is becoming evident that they could also participate in the resistance to treatment.

The selected candidate will work with highly complex combinatorial libraries derived from protein domain scaffolds and will use methods of directed evolution of proteins and selection techniques for the identification of promising small protein binders targeting PD-L1 oncomarker and PD-1 T-cell receptor for improved diagnostic of non-small cell lung cancer (NSCLC). He/she will be responsible for protein production, characterization of selected variants by biochemical and biophysical methods, ELISA-related approaches and by LigandTracer-assisted cell-surface binding assay. Tissue penetration of the developed protein diagnostics will be verified in relevant mouse models. The candidate will also be involved in testing of best protein binders in clinical samples of NSCLC patients in collaboration with Faculty Hospital in Olomouc.

Increasing antibiotic resistance makes the discovery of new antimicrobial compounds an important issue in recent years. An important source of antimicrobials are microorganisms from environmental sources. The PhD project will focus on the regulation of antimicrobial production with emphasis on the role of bacterial ABCF (ATP Binding Cassette, family F) ATPases, group of ribosomal proteins which includes both translation regulators and antibiotic resistance proteins. Our recent findings show one of the ABCFs to regulate antibiotic biosynthesis in response to antibiotic in the environment. By a combination of genetic and proteomic approaches, the project will expand understanding of bacterial ABCF proteins especially their role secondary metabolite regulation.

Myelodysplastic syndromes (MDS) are disorders of hematopoietic stem cell that upon combinatorial effects of germinal and somatic mutations acquire growth advantage leading to acute leukemia. Central to it is the disruption of myeloid transcriptional network and epigenetic apparatus that modulate association of transcription factors with DNA. The heterogeneity of MDS is very large and it influences also the response to therapy. Most effective in MDS appears to be the therapy with DNA methylation inhibitors. Our laboratory has a long-standing interest in MDS pathobiology. We study how MDS cells develop resistance to DNA methylation inhibitors and seek to better understand how we can modulate the MDS response by blocking the newly developed therapeutic resistance.

Immune system has evolved to protect the body from invading pathogens and cancer. Yet aberrant inflammation can lead to severe autoimmune diseases. In order to properly regulate activation and termination of the immune responses, individual cells must communicate with each other and provide the information about ongoing inflammation. One means of communication is the production of small soluble proteins termed cytokines, that are detected by specific receptors on target cells. Proper sensing of these cytokines allow immune cells to activate adequate immune reaction. On the other hand, erroneous response to the cytokine stimulation can lead to severe autoimmunity. The present research aims to uncover new molecular mechanisms how crucial pro-inflammatory cytokines signal and identify new possible venues to modulate their activity in the case of autoimmunity.

The ability of cells to sense mechanical properties of surrounding environment is crucial for many physiological as well as pathological processes includin.

Src kinase plays an important role in a multitude of fundamental cellular processes and is often found deregulated in tumors. Despite the scattered nature of the data, growing body of evidence emerges indicating the importance of Src kinase also in mechanotransduction. In this context, Src, in tight cooperation with primary sensors and the cytoskeleton, functions as an effector molecule necessary for transformation of mechanical stimuli into biochemical outputs executing cellular response and adaptation to mechanical cues.

The malignancy of solid cancer is mainly caused by the ability of tumor cells to form metastases. The crucial step during metastasis is the invasion of the cancer cells through the ECM. To achieve this, cancer cells can utilize the protease-dependent mesenchymal invasion mode or more recently discover the amoeboid mode that relies on enhanced cell contractility. All modes of cancer cell invasiveness are interconvertible and could be employed by cancer cells in combination. A great deal of effort of the worldwide scientific community has been devoted to studying various aspects of cell invasion and migration.

PhD project will focus on identification of factors (co-regulators, metabolites) involved in interactions among cells within structured populations, interactions with the environment and expansion of cells with new properties within the structure. Methodical approaches will include construction of knockout strains and strains with proteins labeled with fluorescent for in situ characterization of specific cell subpopulations using fluorescent and confocal microscopy, metabolite identification, genome-wide proteomics/ phosphoproteomics and other methods of molecular biology, microbiology and biochemistry.

Polymastix and Saccinobaculus are genera of non-culturable oxymonads (anaerobic flagellates) living in the gut of insects. Like their relatives, they probably do not contain any mitochondria. On the other hand, they carry obligatory prokaryotic symbionts on their surface or in their cytoplasm. Their biology and roles in the insect gut are unknown. Our team managed to obtain shotgun reads from amplified gDNA of several separately isolated cells of Polymastix melolonthae and Saccinobaculus sp by single-cell genomics and next-generation sequencing methods. In addition to eukaryotic reads, these datasets contain also reads derived from prokaryotic symbionts and, of course, reads derived from contaminants present in the gut.

Within the group of Preaxostyla flagellates, a unique evolutionary event occurred – the loss of mitochondria in a subgroup of oxymonads, all of which live in the intestines of various animals. The free-living genera Trimastix and Paratrimastix form 3-4 lines branching off before diversification of amitochondriate oxymonads. All appear to contain mitochondria in the forms of small vesicles without cristae, reminiscent of the hydrogenosomes of trichomonads. Understanding the function of these organelles is useful in the context of their loss in related oxymonads. We are interested to know what functions or metabolites these simplified organelles provide to the cells and why oxymonads have stopped using them. So far, the mitochondrial organelle in T. marina has been partially examined and in our laboratory we are thoroughly studying the P. pyriformis organelle by spatial proteomic methods. In T. eleionoma and a new undescribed lineage called "Pacman", the organelle has not been studied yet.

In single-celled algae, cycles of day and night necessitate a metabolic rewire for an optimal use of energy. Algae of the genus Euglena are known for their capability to thrive in both illuminated and dark conditions using organic carbon as a source of energy, which prompts their use in future bioreactors. Our team aims to determine if and how much CO2 fixation contributes to biomass in dark-grown Euglena. Candidates will be encouraged to learn basic and advanced methods of molecular biology and biochemistry, such as aseptic work, genetic manipulations, microscopy, physiological measurements and proteomics. We will also overlook following data analyses and evaluations. The project is scalable according to the candidate’s preferences.

How does a eukaryote function without mitochondria? How are the essential cofactors of proteins, Fe-S clusters, synthesised? We use molecular and biochemical techniques to solve the riddle of how evolution eliminated mitochondria from Monocercomonoides exilis. While working on the project, you would learn molecular cloning and protein expression in prokaryotes and eukaryotes, cell culture, immunofluorescence microscopy, immunoprecipitation amongst others. Do not hesitate to contact us for a chat!

The proposed PhD project will focus on understanding the mechanism of sensing MPyV and human BKPyV genomes by DNA sensor p204/IFI16 and uncovering the role of cGAS association with polyomavirus minichromosomes in the cell nucleus. Confocal, super resolution and immunoelectron microscopy will be used to follow i) dynamics and spatial and functional organisation of IFI16/p204 and cGAS interactions, ii) IFI16/p204 and STING dynamics of trafficking after their activation and iii) the possible interaction of cGAS with viral nucleosomes as well as with cellular SMC5/6 complex and other proteins associated with viral genomes during replication and DNA damage response. Western blot, co-immunoprecipitation, pulldown assays and mass spectroscopy will be used for further identification of cGAS and p204/ IFI16 interacting partners and for studies of posttranslational modifications of IFI16, cGAS and STING.

Immunity depends on leukocyte ability to migrate within lymphoid organs and peripheral tissues. We will work at the interface between cell biology and immunology and study how leukocytes distinguish various environmental cues and interpret them in their migratory behavior. Our primary focus are mechanical aspects – we want to understand how leukocytes recognize physical stress, overcome obstacles or navigate in topologically complex environments. To this end, we will use combination of reductionistic approaches (microfabricated artificial environments, microfluidics) with various types of imaging.

Understanding the different ways in which epigenetic signals and transcription factor networks govern self-renewal, cell specification, differentiation, and reprogramming is a key step for advances in cell-based therapy and perspectives for medicine. Using mouse models, we aim to investigate how elimination and miss-expression of Isl1 and Neurod1 transcription factors affect epigenetic landscapes and downstream targets during embryonic development. We will use Cre/loxP and Crispr/Cas9 technologies, global gene expression profiling (RNA sequencing), CUT&RUN chromatin profiling, FACS, confocal microscopy, immunohistochemistry, and in situ hybridization to evaluate embryonic phenotypes.

The project will address the role of SIRT3 in mitochondrial function and metabolism and its impact on cancer resistance. The aims of this project are (1) To delineate the role of SIRT3 on mitochondrial function and metabolism through its overexpression and knock -down by CRIPR/Cas system (2) To identify important regulatory sites of SIRT3 by directed mutagenesis and test novel isoforms (3) To assess the role of SIRT3 on cell cycle progression and quiescence (4) To unveil the role of SIRT3 and its novel isoforms in cancer resistance. Tamoxifen resistance will be the main model due to its high clinical relevance.

The project is aimed at structure-function studies of anterograde transport mediated by conventional kinesins and their interactions with cargo molecules. We will use a bottom-up approach to analyze a kinesin/cargo transport system at the molecular level. To this end, we will express and purify individual protein components to reconstitute kinesin/cargo complexes and analyze their structural and functional properties. We will apply mutagenesis, biophysical approaches (microscale thermophoresis, analytical ultracentrifugation, SPR, FRET) and structural biology techniques (hydrogen/deuterium exchange, X-ray crystallography, SAXS, cryoEM) to pinpoint motifs mediating cargo/kinesin interactions and delineate the interaction interface(s).

The heat shock protein 90 (HSP90) is a molecular chaperone regulating proteostasis under both physiological and stress conditions in eukaryotic cells. Cellular functions of HSP90, such as conformational cycling and interactions with client proteins and co-chaperones, are modulated by a host of post-translational modifications, including lysine acetylation. Several acetylation sites of HSP90 have been identified by whole proteome mass spectrometry approaches and biological data suggest that histone deacetylase 6 (HDAC6) can be the principal deacetylase and a client protein of the HSP90 chaperone machinery. However, structural basis of HSP90 (de)acetylation by HDAC6 as well as functional consequences of such interactions have not been studied at the molecular level. We will use synthetic biology, structural and biophysical techniques as well as cell-based assays to unravel how the HSP90 structure and function are regulated by lysine acetylation.

Signaling by the PI3K (phosphatidylinositol-3-kinases)/AKT (protein kinase B) pathway is essential and highly regulated in lymphomas, being frequently upregulated by oncogenic mutations. The link of PI3K/AKT activity to the cell cycle is well established. Using genetically encoded biosensor of AKT activity, we have precisely documented the exact variation of the AKT activity through the cell cycle and proved that this variation is essential for the cell cycle progression. However, details about the oncogenic potential of the AKT-cell cycle link and regulation in lymphoma are missing.

Application form

The first step is to choose PhD project(s) and thus the laboratory(ies) that the applicant would like to join for his/her PhD study. The applicant must then complete on-line Application and submit it. The submitted Application will receive PhD project leader(s), who might then contact the applicant and agree on further steps (e.g. online interview etc.). In a case of mutual interest then the applicant upon agreement with the project leader submits formal application for PhD study to the relevant special board. He/she will then be invited to formal interview (likely online, usually in June) at this board for the acceptance to PhD study – see also Practical notes to PhD study – HERE.

Considered PhD positions ?
Undergraduate education
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Exams & Grades ? Final examination(s) for the Master's degree
Final examination(s) for the Bachelor degree
Most relevant subject exams degree ?
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Research experience
Additional reference
Achievements ?
Skills
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Something about yourself ?
gdpr      

Contacts

RNDr. Ladislav Anděra, CSc. RNDr. Ladislav Anděra, CSc.

RNDr.
Ladislav Anděra, CSc.

PhD Program Coordinator

ladislav.andera@ibt.cas.cz
+420325873796
Mgr. Petr Solil Mgr. Petr Solil

Mgr.
Petr Solil

Head of Communications and Spokesperson

petr.solil@ibt.cas.cz
+420325873143