BIOCEV
PhD study at BIOCEV centre
The PhD education at the BIOCEV Centre facilitates postgraduate studies in the fields of biotechnology and biomedicine. Multiplicity of laboratories with diverse backgrounds have found home in the BIOCEV Centre, belonging namely to the two faculties of the Charles University (1st Faculty of Medicine and Faculty of Science) and the Institute of Biotechnology of Czech Academy of Science (CAS), as well as laboratories of five other CAS institutes – the Institute of Molecular Genetics, the Institute of Microbiology, the Institute of Physiology, the Institute of Experimental Medicine, and the Institute of Macromolecular Chemistry. All these combined create the BIOCEV Centre.
In addition to their research work, the scientific and professional staff of the BIOCEV Centre directly supervise PhD students, of whom over 300 currently work at BIOCEV, and are also involved in the education of both undergraduate and graduate students. In more than 50 laboratories at the BIOCEV Centre, students learn experimental techniques and scientific methodologies under the guidance of experienced experts, which they may apply in a wide range of professional scientific work.
Open position for PhD student at BIOCEV for the academic year 2022-2023.
For more detail information on individual PhD study projects, please visit our website:
https://www.biocev.eu/en/education/phd-programme.1#education-positions
Laboratory: Genomics of Eukaryotes and Lateral Gene Transfer
Group leader : Vladimir Hampl
Website: https://www.biocev.eu/en/research/cellular-biology-and-virology.4/genomics-of-eukaryotes-and-lateral-gene-transfer.40
Project 1 title:
Supervisor: Vladimir Hampl
Project title: Development of an algorithm for prediction of protein targeting in Euglena gracilis
Brief description of the project:
Euglena gracilis contains a secondary green plastid covered with three membranes. The mechanism by which proteins are targeted to plastid is not entirely clear, as is the actual process of transporting these proteins across envelope membranes. The time is so mature to develop an algorithm that, based on our knowledge and using a training set of credible plastid and mitochondrial proteins, would learn how to recognize plastid, mitochondrial and ER-targeted proteins of E. gracilis and implement it in a software with a user-friendly interface. Such a tool would help to refine the proteomes of E. gracilis organelles and to estimate organellar proteomes in related euglenas.
Project 2 title: Protein composition of the cytoskeleton of excavates
Supervisor: Vladimir Hampl
Brief description of the project: Very little is known about the protein composition of the non-actin and non-tubulin cytoskeleton of protists, i. e. the different types of intermediate and striated fibrils. Yet, this knowledge could allow the homology of some morphological structures across distant groups and answer the question of what the ancestor of eukaryotes (LECA) looked like. We believe that the methodology has matured to a stage where it is possible to start asking such questions, so let’s do something about it.
Laboratory: Lymphoma Tumor Biologyryotes and Lateral Gene Transfer
Group leader: Ondrej Havranek
Website: https://havranek-lab.lf1.cuni.cz/about-us
Project title:
Supervisor: Ondrej Havranek
Project title: Functional characterization of lymphoma associated mutations identified by analysis of circulating tumor DNA.
Brief description of the project:
We aim to identify lymphoma associated DNA mutations relevant to its biology, aggressiveness, response to treatment, or relapse prediction by analysis of circulating tumor DNA. In the next step, the aim is to functionally characterize identified genes and mutations in relation to their function in lymphomas to provide molecular biology explanation of identified associations.
Laboratory: Molecular Oncology
Group leader : Radoslav Janostiak
Website: https://www.biocev.eu/en/research/cellular-biology-and-virology.4/laboratory-of-molecular-oncology.70
Project title:
Supervisor: Radoslav Janostiak
Project title: Spatiotemporal regulation of cancer cell quiescence
Brief description of the project:
Two PhD positions are available in the newly established Laboratory of Molecular Oncology. Projects will be focused on the spatiotemporal regulation of the transition between quiescence and proliferation of cancer cells. Experiments will be carried out using advanced proteomics, transcriptomics and microscopy methods on the 3D cancer organoid cultures.
Laboratory: Mechanisms involved in remodeling of chromatin structure during cell fate decisions/Stopka lab
Group leader : Tomas Stopka
Website: https://stopka-lab.lf1.cuni.cz/en/about-our-lab and https://www.biocev.eu/en/research/functional-genomics.3/mechanisms-involved-in-remodeling-of-chromatin-structure-during-cell-fate-decisions.63
Project title:
Supervisor: Tomas Stopka
Project 1 title: Role of chromatin remodelling complexes in development
Brief description of the project:
The manipulation expression of ISWI chromatin remodeling ATPase/helicase Smarca5, a member of multiple SWI/SNF complexes, in adult hematopoietic stem cells leads to loss of lymphoid (B and NK/T) differentiation potential in a dose-dependent manner. On the other hand, the conditional inactivation of during fetal liver development leads to defective differentiation of adult-definitive hematopoietic progenitors and accumulation of non-functional hematopoietic stem cells, implying a role in the maintenance of adult-definitive hematopoietic stem cell populations. Besides its role in hematopoiesis, Smarca5 remodeling factor has additional roles during early post-implantation development, neurogenesis, and maintenance of adult tissue stem cells in highly dividing populations. Using a transgenic mouse model expressing N-terminally tagged Smarca5 protein we have recently identified numerous known as well as previously unknown interaction partners in these tissues. The mechanism by which chromatin remodeling activity of Smarca5 regulates development is not entirely known, nevertheless the role of interaction partners is indispensable in this respect as many of these proteins recognize specific histone marks that control the expression of many tissue-specific transcription factors and their target genes. Study of genetic interaction of Smarca5 and its binding partners, identification of common genome-wide localization and integration with transcriptional and chromatin accessibility data would help to refine our understanding of ISWI remodeling function in the epigenetic regulation of transcription during development.
Project 2 title: Molecular Aspects of Normal and Malignant Hematopoiesis
Supervisor: Kristyna Pimkova
Brief description of the project:
Hematopoiesis is a dynamic and complex hierarchical system of blood cell production from hematopoietic stem cells. The accumulation of genetic mutations in hematopoietic stem cells causes the loss of their ability to differentiate into mature blood cells and leads to the accumulation of clonal myeloid progenitors, which is called acute myeloid leukemia (AML). AML arises de novo or secondary to myelodysplastic syndrome (MDS) and is the most common acute leukemia in adults. Intensive treatment with chemotherapy is often hampered by the development of drug resistance and most, particularly older individuals, have a poor prognosis and survival. Increasing evidence and our data suggest that reactive oxygen species (ROS)-mediated signaling plays a key role in the mechanisms that initiate leukemia and is also involved in events that mediate development of leukemia cell resistance to treatment. Applying proteomic approaches, we characterized redox signaling events in developmental hematopoiesis and in early stages of leukemia initiation and identified redox switches that contribute to loss of cellular response to therapy. ROS through modification of their thiol residues altered function of proteins with a pronounced role in regulation of cell death, metabolism, protein homeostasis and other fundamental processes of normal and malignant hematopoiesis hematopoiesis. We believe that our further work in this field will significantly contribute to our understanding of another layer of regulation of malignant hematopoiesis and improve current therapeutic approaches.
Laboratory: Cellular Metabolism
Group leader : Katerina Rohlenova
Website: https://www.ibt.cas.cz/en/research/laboratory-of-cellular-metabolism/
Project title:
Supervisor: Katerina Rohlenova
Project 1 title: Nucleotide metabolism crosstalk in cancer
Brief description of the project:
Cancer cells rewire their metabolism to satisfy the demands of rapid proliferation, and cancer metabolism represents an attractive target. Historically, one of the first approaches to fight cancer was antimetabolite therapy that interferes with metabolism of nucleotides. But still today, antimetabolite therapy suffers high rates of resistance and leads to toxicity in healthy tissues. Tissues consist of number of cell types, which metabolically communicate. This crosstalk enables survival in nutrient-poor environments, such as in tumors and may limit the efficacy of metabolic interventions. The cellular sources of nucleotides and their building blocks are poorly understood. Our main goal is to uncover how cells in tissues trade nucleotides and their building blocks. Such knowledge could guide new strategies that will overcome the resistance and toxicity. To reach this goal you will study the metabolic interactions in tissues of genetic mouse models of perturbed nucleotide biosynthesis, using metabolic approaches, and single cell & spatial omics.
Laboratory: Structural Biology
Group leader : Cyril Barinka
Website: https://www.ibt.cas.cz/en/research/laboratory-of-structural-biology/
Project title:
Supervisor: Cyril Barinka
Project 1 title: Molecular interactions between Dishevelled 3 (Dvl3) and cytoskeleton
Brief description of the project:
Dvl3 is a scaffolding protein involved in Wnt signalling pathways that are essential for both correct embryo development and tissue homeostasis in adulthood. We have recently identified a new interacting partner of Dvl3 that tethers Dvl3 to microtubules. This project is focused on uncovering molecular basis of Dvl3 interactions with microtubule cytoskeleton and physiological significance of such interactions. The project involves both in vitro reconstitution of the Dvl3-tether-microtubule complex as well as complementary cell-based studies elucidating physiological role(s) of Dvl3/microtubule interactions in vivo.
Project 2 title: Genetic code expansion in the search for novel substrates of histone deacetylase
Supervisor: Cyril Barinka
Brief description of the project:
The genetic code expansion allows for the targeted incorporation of non-canonical amino acids into the primary sequence of proteins. The aim of the project is to use this methodology for biochemical and biophysical characterization of interactions between heat shock protein 90 (HSP90) and human histone deacetylase 6 (HDAC6). Biological data suggest that HDAC6 is a principal deacetylase and a client protein of HSP90, but structural basis of HSP90 (de)acetylation by HDAC6 and functional consequences of such interactions have not been studied. The project shall provide mechanistic underpinnings of how cellular functions of HSP90 are regulated by reversible lysine acetylation with the special focus on the involvement of HDAC6.
Project 3 title: Mechanisms of cargo recognition by kinesin molecular motors
Supervisor: Cyril Barinka
Brief description of the project:
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 total internal reflection microscopy will be used to visualize the complexes and elucidate their functional properties up to the single molecule level in vitro. Finally, neuronal cell-based assays will be exploited to translate and validate in vitro data in a physiologically relevant environment of the axonal transport. Overall, we expect our data to contribute to our understanding of general molecular mechanisms governing kinesin activation and principles of a protein transport in (neuronal) cells.