PhD Programme

PhD Programme

RNDr. Ladislav Anděra, CSc.

RNDr. Ladislav Anděra, CSc.

About us

The PhD programme 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 150 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.

The aim of postgraduate training is not only to deepen knowledge in the chosen field, but also to acquire practical laboratory skills, including planning, conducting and evaluating a scientific experiment, writing scientific publications or student research projects. Similarly important is learning to present one's own scientific results and, last but not least, to develop critical thinking skills.

News

Notes

If some of the open PhD positions has caught your interest and you have also found agreement with your future supervisor, you need to submit a formal application for PhD studies in Biomedicine (usually by the end of April) and then successfully pass the admission interview in front of the PhD committee (usually during June).

Accepted PhD applicants begin their studies within their chosen Biomedical PhD programme, based either in the Faculty of Science or one of the Charles University's medical faculties. Although the selected PhD programme may slightly differ in its specific requirements, all the incoming PhD students must, in coordination with their supervisor, develop an individual study plan consisting of lectures, courses, and presentations at conferences (either student, national or international level). Similarly, one hones his/her skills in preparation and submission of manuscripts and, last but not least, passing the PhD examination in front of the supervisory committee.

PhD studies are usually four years long (maximum is nine years) and are funded partly by a PhD scholarship from the relevant faculty and partly by an employment contract with the supervisor's department. Successful completion of the PhD programme requires at least one first-author publication in a peer-reviewed journal with an appropriate impact factor (or multiple co-authored publications) and a successful defense of the PhD thesis. However, the specific obligations are described by the respective disciplinary boards that organize the individual fields of study.

Open PhD Projects

The newly opened positions for PhD students in the BIOCEV research laboratories for the academic year 2022/2023 are listed below, together with links for more detailed information about the individual projects. For those of you who would be interested in some of these projects, please fill in the attached application form, choosing of up to three PhD projects (you will also find a link to data protection - GDPR - at the bottom right of the application form). Your completed application form will be forwarded to the supervisors of the selected PhD projects. After the submission they can contact you about the details of the projects and arrange a follow-up formal application for PhD programme for the selected projects.

PhD Project Project Leader Laboratory

PKN kinases belong to family of PKC kinases and are involved predominantly in regulation of cytoskeletal organization as effector proteins of Rho family of small GTPases. Unlike other PKN kinases, PKN3 is physiologically expressed mostly in primary endothelial cells and osteoclasts but is also often overexpressed in cancer cells. Recently, PKN3 was found to be surprisingly enriched in mitochondria. The aim of the project will be to analyze a potential PKN3-mediated crosstalk of Rho signaling and mitochondrial physiology.

The project aims to analyze the role of Src kinase in the physiology of osteoclasts, especially in the formation of sealing zones. Src activity and dynamics in the osteoclast sealing zone will be analyzed in living osteoclasts using our Src-FRET biosensor. CRISPR/Cas9 knock-in strategies will be used to prepare monocytes expressing the Src-FRET biosensor under an endogenous promoter.

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.

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.

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.

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.

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.

2 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.

We 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.

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.

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.

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.

Application form

The first step is to choose the PhD project(s) with the laboratory(-ies) where the PhD candidate would be interested in performing the PhD studies. Next, the candidate fills-in the online Application Form below and submits it. The completed application form will be received by the PhD project supervisor(s), who will then, at their discretion, contact the PhD candidate to discuss the next steps (e.g. online interview, etc.). Upon finding mutual interest, the candidate will then, in agreement with the project supervisor, submit a formal application for a PhD programme to the relevant university board, where the PhD applicant later undergoes admission interview for the PhD studies (usually in June).

The deadline for submitting the application within the BIOCEV Centre is 28th of February 2022, after acceptance to the selected project it is necessary to submit the application for the relevant PhD programme by 30th of April 2022 in the case of faculties of Charles University.

Considered PhD positions ?
Undergraduate education
Graduate (Master’s degree)
Exams & Grades ? Final examination(s) for the Master's degree
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Research experience and skills
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Additional reference
Achievements ?
Something about yourself ?
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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
RNDr. Kristýna Pimková, Ph.D. RNDr. Kristýna Pimková, Ph.D.

RNDr.
Kristýna Pimková, Ph.D.

Research Associate & Deputy Head

kristyna.pimkova@lf1.cuni.cz
+420325873026