Life Sciences

This doctoral study programme is organized by the Faculty of Science in English and the studies are subject to tuition. There is an alternative option for the international applicants to be accepted in the free programme administered in Czech with the possibility of receiving a scholarship. The study language of the programme is still English (Czech is the administrative language). Before officially applying, please contact us at admission@sci.muni.cz to find all the necessary information related to the scholarship and see our FAQ’s.

Podat přihlášku

Přijímací řízení do doktorského programu Life Sciences 2023/2024 (zahájení podzim 2023)
Termín podání přihlášky do půlnoci 28. 2. 2023.

Co se naučíte

The aim of the study is to educate students in the field of life sciences and to prepare them as highly qualified specialists for scientific activities. The introductory part of the study concentrates on deepening theoretical and practical knowledge. At the same time, separate literary research on the assigned topic of the doctoral dissertation is being prepared. The core of students’ activities lies in their own scientific work. Students are guided by the supervisor to be able to independently implement all phases of a scientific project. They are also encouraged to the processing of the obtained experimental data methodologically relevant, as well as to their interpretation and subsequent presentation in various forms. The programme is highly multidisciplinary and, compared to the traditional study of biology, is more methodologically and analytically focused. Thanks to access to state-of-the-art infrastructure, students can better combine various biochemical, bioanalytical and visualization instrumental techniques with solving biological problems, which increases the impact of their scientific activities and their flexibility in the labor market, including positions in academia, e.g. within existing biotechnology companies or in newly emerging spin-offs.

Life for Science. Science for Life.

The concept of the programme reflects the current level of scientific knowledge, the needs of the labor market, and overall trends in the field. At the same time, it benefits from the support system within the so-called CEITEC PhD School, which presents the concept of care for doctoral students involved in research teams at CEITEC and at the same time emphasizes expanding the competencies of the future graduates in socio-managerial, technological and soft skills. That will enable them to conduct their follow-up research in an efficient and modern way and provide them with a very good overview of the ethical aspects of research necessary for life sciences research and research and development in general.

The programme aims at the international employment of graduates. It is prepared in Czech and English versions, most subjects are taught, all seminars and, to a large extent, research is conducted in English. The environment at CEITEC MU is significantly international, so students are exposed to communication in English not only during official teaching but practically everywhere within CEITEC.

Praxe

An important contribution to the acquisition of practical skills of DSP students of Life Sciences is their natural involvement in research teams at CEITEC MU. In this way, students can immediately acquire the necessary practical skills for team management and research projects, acquire networking skills and directly engage in research projects and grants (including H2020 projects and ERC grants) to understand the issues of research funding. Students can also routinely use eleven uniquely equipped shared laboratories and gain significant practical experience in this form within the so-called internal internship, or in another institution in the Czech Republic as part of an external internship (recommended volume is 10 working days (80 working hours).

A compulsory part of the study obligations in the doctoral study program is completing part of the study at a foreign institution for at least one month, or participating in an international creative project with results published or presented abroad or another form of student direct participation in international cooperation.

The program supports Collaborative PhD, i.e. completing a doctoral project in cooperation with a commercial entity. That allows students to expose themselves to a more non-academic environment. Also, within the TAC system, students cooperate more often with experts from practice.

Chcete vědět víc?

http://ls-phd.ceitec.cz/

Uplatnění absolventů

In the doctoral programme, great emphasis is placed on internationalization, there are also conditions for interdisciplinary solutions to the assigned topics of the dissertation, and the emphasis is placed on strengthening socio-managerial and soft-skills. This increases the real chances of graduates to apply in top scientific and technological, academic and commercial teams around the world, such as in:

  • research organizations and academic institutions (research institutes, universities) focusing on biological and biomedical research and education, in the first years as the postdoctoral trainees and subsequently as the leaders of a research team or programme, the heads of shared laboratories (so-called facilities), etc., or at lecturer positions;
  • cutting-edge laboratories of applied research focused on the development of new biotechnological biomedical methods, in the scientific specialists and developers’ positions;
  • the commercial sphere in the field of consulting and marketing of biomedical or biotechnological products;
  • thanks to acquired knowledge in the field of intellectual property and technology transfer specifically in their areas of interest, graduates of the field will be well equipped for activities in establishing start-ups and spin-off companies.

Podmínky přijetí

Requirements are specified in detail here. The admission procedure is carried out in two rounds. The first round is based on the application and background information - only complete applications with all mandatory parts will be accepted and reviewed. The applicants selected for the next round will be invited for the admission interview with the committee. Please check your e-mails, including spam folders.

Termíny

1. 12. 2022 – 28. 2. 2023

Termín pro podání přihlášek

Podat přihlášku

Výzkumná zaměření dizertačních prací

Jednooborové studium

Computational simulations of the conformational changes within Tau protein and its fibrilization
Školitel: doc. RNDr. Mgr. Jozef Hritz, Ph.D.

The main neuropathological signs of Alzheimer’s disease are associated with the fibrillization of tau protein into neurofibrillary tangles. Studying how different factors influence the formation of protein fibrils is the key to understanding these neurodegenerative processes. The main aim of this PhD project will be computational simulations of conformational changes within the Tau protein and the fibrilization processes. The details of the conformation changes and the fibrilization induced by the phosphorylation, buffer conditions, truncation, or the interaction with the client proteins like 14-3-3s will be studied by molecular dynamics at the atomistic and the coarsegrained level. The obtained theoretical predictions will be validated with the experimental data provided by the biomolecular NMR and the biophysical methods. The described activities are part of international research projects allowing to spend the part of PhD study in the groups of our collaborators in Europe or North and South America and to learn specific research techniques, there.

Requirements on candidates:

preferable candidate’s background in biophysics, computational chemistry, or physical chemistry.

PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor or/and fill in the registration form on the web page of the CEITEC PhD School (link below).

MORE INFORMATION:

http://ls-phd.ceitec.cz/

https://www.ceitec.eu/protein-structure-and-dynamics/rg110/tab?tabId=21

Poznámky

Recommended literature:

Trosanova Z., Lousa P., Kozelekova A., Brom T., Gasparik N., Tungli J., Weisova V., Zupa E., Zoldak G., Hritz J.*: Quantitation of human 14-3-3zéta dimerization and the effect of phosphorylation on dimer-monomer ekvilibria. J. Mol. Biol. 2022, 434, 167479

Zapletal, V.; Mládek, A.; Melková, K.; Louša, P.; Nomilner, E.; Jaseňáková, Z.; Kubáň, V.; Makovická, M.; Laníková, A.; Žídek L.; Hritz, J.* Choice of force field for proteins containing structured and intrinsically disordered regions. Biophys. J. 2020, 118, 1621 – 1633.

Pavlíková Přecechtělová J., Mládek A., Zapletal V., Hritz J. Quantum Chemical Calculations of NMR Chemical Shifts in Phosphorylated Intrinsically Disordered Proteins, JCTC 2019, 15, 5642-5658.

Jandova Z; Trosanova Z.; Weisova V.; Oostenbrink C., Hritz J.*: Free energy calculations on the stability of the 14-3-3zéta protein. BBA - Proteins and Proteomics, 2018, 1866, 442-450.

Nagy G., Oostenbrink C., Hritz J.*: Exploring the Binding Pathways of the 14-3-3zéta Protein: Structural and Free-Energy Profiles Revealed by Hamiltonian Replica Exchange Molecular Dynamics with Distance Field Distance Restraints. PLoS ONE 2017,12(7), e0180633.

Školitel

doc. RNDr. Mgr. Jozef Hritz, Ph.D.

Correlative light and electron microscopy of transcription condensates
Školitel: prof. Mgr. Richard Štefl, Ph.D.

Correlative Light Electron Microscopy (CLEM) uses a combination of an optical (fluorescence) microscope and a cryo-electron microscope. Two images of the sample are taken simultaneously – one with the optical light, the other with the electron beam. This technology allows to capture not only dynamic changes but also the molecular ultrastructure of living systems. New developments in accurate positional referencing of specimens on mounting grids, advances in the instrumentation, and the availability of software packages for cross-platform data correlation allow to image the ultrastructure of nucleolar sub-compartments and to track specific proteins found in phase-separated organelles.

In this project, we will implement the CLEM technology to investigate and visualize phase-separated organelles involved in transcription by RNA polymerase II and investigate their regulatory mechanism during transcription. This biophysically focused project will also involve other imaging approaches, including single-particle reconstruction cryo-electron microscopy and cryo-electron tomography, which will help to obtain an overall picture of condensate-based transcription at different resolutions. The project is linked to the CEITEC's teaming project CORMIC – bridging academia and industry in correlative microscopy.

PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor or/and fill in the registration form on the web page of the CEITEC PhD School (link below).

MORE INFORMATION:

http://ls-phd.ceitec.cz/

https://stefl-lab.ceitec.cz/

Poznámky

Recommended literature:

Mediator and RNA polymerase II clusters associate in transcription-dependent condensates Won-Ki ChoJan-Hendrik SpilleMicca HechtChoongman LeeCharles LiValentin GrubeIbrahim I. Cisse Science, 361 (6400), DOI: 10.1126/science.aar4199.

Zhang et al Molecular Cell (2022), https://doi.org/10.1016/j.molcel.2022.06.032.

Nievergelt et al., COSB, 2019, https://doi.org/10.1016/j.sbi.2019.06.008.

Školitel

prof. Mgr. Richard Štefl, Ph.D.

Designing modified DNA fragments
Školitel: prof. RNDr. Radek Marek, Ph.D.

Novel forms of nucleotides will be incorporated in silico in oligomers with sequences relevant for biosystems. The biocompatibility of artificial building blocks will be evaluated using advanced methods of quantum chemistry (that provide also analytical tools for investigation of crucial noncovalent interactions) and molecular dynamics. Available candidates of modified nucleobases and sugars will be investigated experimentally by using NMR spectroscopy in solution.

Requirements on candidates:

Computational and quantum chemistry, structural chemistry or biology.

PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor or/and fill in the registration form on the web page of the CEITEC PhD School (link below).

MORE INFORMATION:

http://ls-phd.ceitec.cz/

https://www.ceitec.eu/structure-of-biosystems-and-molecular-materials/rg108/tab?tabId=22

Poznámky

Recommended literature:

CUYACOT, Ben J.R., Ivo DURNÍK, Cina FOROUTAN-NEJAD and Radek MAREK. Anatomy of Base Pairing in DNA by Interacting Quantum Atoms, Journal of Chemical Information and Modeling, 2021, 61, 211-222. doi:10.1021/acs.jcim.0c00642.

YURENKO, Yevgen, Jan NOVOTNÝ and Radek MAREK. Weak Supramolecular Interactions Governing Parallel and Antiparallel DNA Quadruplexes: Insights from LargeScale Quantum Mechanics Analysis of Experimentally Derived Models. Chemistry - A European Journal, 2017, 23, 5573-5584. doi:10.1002/chem.201700236.

DUREC, Matúš, Francesco ZACCARIA, Célia FONSECA GUERRA and Radek MAREK. Modified guanines as constituents of smart ligands for nucleic acid quadruplexes. Chemistry - A European Journal, 2016, 22, 10912-10922. doi:10.1002/chem.201601608.

BAZZI, Sophia, Jan NOVOTNÝ, Yevgen YURENKO and Radek MAREK. Designing a New Class of Bases for Nucleic Acid Quadruplexes and Quadruplex-Active Ligands. Chemistry - A European Journal, 2015, 21, 9414-9425. doi:10.1002/chem.201500743.

YURENKO, Yevgen, Jan NOVOTNÝ, Vladimír SKLENÁŘ and Radek MAREK. Substituting CF2 for O4' in Components of Nucleic Acids: Towards Systems with Reduced Propensity to Form Abasic Lesions. Chemistry - A European Journal, 2015, 21, 17933-17943. doi:10.1002/chem.201502977.

Školitel

prof. RNDr. Radek Marek, Ph.D.

Development of bioinformatics methods for analyzing RNA modifications with long-read nanopore sequencing
Školitel: Mgr. Vojtěch Bystrý, Ph.D.

Post-transcriptional RNA modification research, also known as epitranscriptomics, is a science field that recently became prominent during the covid pandemic for its role in immune response mediation. The role of epitranscriptomics in cancerogenesis is also very much studied.

In CEITEC MU, several research groups are trying to understand the biological role of RNA modifications.

An emerging method to study RNA modification is nanopore sequencing because the long-read sequencing can better capture the whole transcripts, but mainly because it allows direct RNA sequencing. However, novel algorithms and methods must be developed to utilize the potential of the method to its full potential. The Ph.D. candidate will collaborate with RNA biology research groups, a genomics core facility to establish methods for long-read sequences and eventually direct RNA sequencing data analysis. The Ph.D. candidate will, through bioinformatics support, facilitate the research of RNA modification concerning the immune response and cancer.

Requirements on candidates:

bioinformatics, informatics, data science

PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor or/and fill in the registration form on the web page of the CEITEC PhD School (link below).

MORE INFORMATION:

http://ls-phd.ceitec.cz/

https://www.ceitec.cz/centralni-laborator-bioinformatika/cf284

Poznámky

Recommended literature:

Quin, Jaclyn, et al. "ADAR RNA modifications, the epitranscriptome and innate immunity." Trends in biochemical sciences 46.9 (2021): 758-771.

Furlan, Mattia, et al. "Computational methods for RNA modification detection from nanopore direct RNA sequencing data." RNA biology 18.sup1 (2021): 31-40.

Školitel

Mgr. Vojtěch Bystrý, Ph.D.

Dishevelled internal affairs in Wnt signalling
Školitel: Konstantinos Tripsianes, Ph.D.

Dishevelled (DVL) is the central hub of Wnt signal transduction that integrates and transduces upstream signals through distinct cytoplasmic cascades. Looking at the many DVL faces reported in the literature, three salient features underlying its function in signalling can be highlighted: (1) it interacts with more than seventy binding partners, (2) it is heavily phosphorylated at multiple sites by at least eight different kinases, in particular by Ck1ε/δ after Wnt stimulation, and (3) it consistently forms puncta in the cytosol, that are phase-separated self-assemblies also called liquid droplets.

Our working hypothesis is that DVL conformational plasticity mediated by the order-disorder interactions allows the combinatorial integration of phosphorylation input, partners binding, self-assembly in droplets, and allosteric coupling, to exquisitely control signal routing. We integrate structural biology (NMR, SAXS, X-ray) and biophysical techniques (FRET, ITC, BLI) with cellular readouts (TopFlash, BRET) to understand DVL structure, function, and regulation. Candidates can choose among three open questions, that if resolved, will have a significant impact on Wnt research. 1) Does disorder provide new contexts to structured domain(s) and, hence, enhance the DVL functional space associated with them? 2) Is there a direction, order or hierarchy in the phosphorylation of individual S/T sites and clusters in DVL? 3) What are the physical behaviours associated with the intrinsic disorder and their connection to DVL liquid-liquid phase separation?

Requirements on candidates:

  • Biomolecular NMR
  • Biochemistry
  • Molecular Cell Biology
  • PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor and phd@ceitec.muni.cz

    MORE INFORMATION:

    http://ls-phd.ceitec.cz/

    https://www.ceitec.eu/protein-dna-interactions/rg111

    Poznámky

    Recommended literature:

    Hanáková K. et al. Comparative phosphorylation map of Dishevelled 3 links phospho-signatures to biological outputs. Cell Commun. Signal., 2019. 17: p. 170

    Harnoš J. et al. Dishevelled-3 conformation dynamics analyzed by FRET-based biosensors reveals a key role of casein kinase 1. Nat. Commun., 2019. 10: p. 1804.

    Školitel

    Konstantinos Tripsianes, Ph.D.

    Functions of cyclin-dependent kinase 11 (CDK11) in regulation of gene expression and tumorigenesis
    Školitel: Mgr. Dalibor Blažek, Ph.D.

    CDK11 is ubiquitously expressed in all tissues and the CDK11 null mouse is lethal at an early stage of development indicating an important role for Cdk11 in the adult as well as during development. CDK11 is believed to play a role in RNAPII-directed transcription and co-transcriptional mRNA-processing, particularly alternative splicing and 3end processing. However, its genome-wide function in regulating the human transcriptome is unknown. Notably, several recent studies identified CDK11 as a candidate essential gene for growth of several cancers therefore, understanding the molecular mechanism(s) of CDK11-dependent gene expression would be also of significant clinical interest. In this research we will use various techniques of molecular biology and biochemistry to characterize genome-wide role of CDK11 in regulation of gene expression and tumorigenesis.

    Requirements on candidates:

    Background in molecular biology, biochemistry or life sciences. Interest in bioinformatics and data analyses is desirable.

    PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor or/and fill in the registration form on the web page of the CEITEC PhD School (link below).

    MORE INFORMATION:

    http://ls-phd.ceitec.cz/

    https://www.ceitec.eu/inherited-diseases-transcriptional-regulation/rg38

    Poznámky

    Recommended literature:

    Gajduskova, P., Ruiz de Los Mozos I, Rajecky M., Hluchy M., Ule J., Blazek D*: CDK11 is required for transcription of replication dependent histone genes. Nature Structural & Molecular Biology 27 (5):500-510 (2020).

    Školitel

    Mgr. Dalibor Blažek, Ph.D.

    Characterization of cyclin-dependent kinase 12 (CDK12) substrates and their roles in regulation of transcription and tumorigenesis
    Školitel: Mgr. Dalibor Blažek, Ph.D.

    Cdk12 is transcriptional cyclin-dependent kinase (Cdk) found mutated in various cancers. In previous studies we found that Cdk12 maintains genome stability via optimal transcription of key homologous recombination repair pathway genes including BRCA1. Apart from the C-terminal domain of RNA Polymerase II other cellular substrates for both kinases are not known. In this research we propose using a screen in cells carrying an analog sensitive mutant of CDK12 to discover its novel cellular substrates. The substrates and their roles in normal and cancerous cells will be characterized by various techniques of molecular biology and biochemistry.

    Requirements on candidates:

    Background in molecular biology, biochemistry or life sciences. Interest in bioinformatics and data analyses is desirable.

    PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor or/and fill in the registration form on the web page of the CEITEC PhD School (link below).

    MORE INFORMATION:

    http://ls-phd.ceitec.cz/

    https://www.ceitec.eu/microenvironment-of-immune-cells/rg115

    Poznámky

    Recommended literature:

    Pilarova K, Herudek J, Blazek D.*: CDK12: Cellular functions and therapeutic potential of versatile player in cancer: Nucleic Acids Research Cancer (Oxford University Press) k2 (1): zcaa003 (2020).

    Chirackal Manavalan A.P., Pilarova K., Kluge M., Bartholomeeusen K., Oppelt J., Khirsariya P., Paruch K., Krejci L., Friedel C.C., Blazek D* : CDK12 controls G1/S progression via regulating RNAPII processivity at core DNA replication genes. EMBO reports 20(9):47592 (2019).

    Ekumi KM, Paculova H, Lenasi T, Pospichalova V, Bösken CA, Rybarikova J, Bryja V, Geyer M, Blazek D*, Barboric M*. Ovarian carcinoma CDK12 mutations misregulate expression of DNA repair genes via deficient formation and function of the Cdk12/CycK complex. Nucleic Acids Research 43(5):2575-89 (2015).

    Bösken CA, Farnung L, Hintermair C, Merzel Schachter M, Vogel-Bachmayr K, Blazek D, Anand K, Fisher RP, Eick D, Geyer M. The structure and substrate specificity of human Cdk12/Cyclin K. Nature Communications 5 (2014).

    Blazek D*., Kohoutek J., Bartholomeeusen K., Johansen E., Hulinkova P., Luo Z., Cimermancic P.,Ule J., Peterlin B.M.: The CycK/Cdk12 complex maintains genomic stability via regulation of expression of DNA damage response genes. Genes and Development 25 (20): 2158-2172 (2011).

    Školitel

    Mgr. Dalibor Blažek, Ph.D.

    Investigating pre-mRNA alternative splicing during the embryonic thermoresponse in Arabidopsis thaliana
    Školitel: Helene Robert Boisivon, Ph.D.

    Transcript variants generated by alternative splicing (AS) of a precursor mRNA transcript expand the cellular protein catalog for the plant response to various stresses without the requirement of de novo transcription. AS is a molecular strategy taken by plants under temperature stress to limit the adverse effects of high temperatures and to adjust their growth and physiology during the stress period. Spliced variants may be targeted for degradation by non-sense mediated decay (NMD) or encode alternative proteins to feedback on the stress response. Heat Shock Proteins (HSP) and Heat Shock Factors (HSF) are among the targets of temperature-induced AS. Our lab investigates how high temperatures affect embryo morphogenesis and seed development. We identified that AS regulators are upregulated in seeds of plants grown at high temperatures. The project will investigate the implications of AS in the morphogenic alterations of Arabidopsis embryos when developing at high temperatures. The proposed experimental approaches include profiling of AS events in high-temperature seeds. Specific candidates whose transcripts are targeted by AS at high temperatures, and known for their involvement in embryo morphogenesis, will be functionally characterized: expression analysis (microscopy), phenotyping (genetics), ectopic expression (cloning, generation of transgenics), etc.

    Requirements on candidates:

    The candidate will have notions of bioinformatics. The candidate has experience in molecular biology (cloning, RT-qPCR), expression analysis (microscopy), and notions of plant genetics and epigenetics.

    PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor or/and fill in the registration form on the web page of the CEITEC PhD School (link below).

    MORE INFORMATION:

    http://ls-phd.ceitec.cz/

    https://boisivonlab.ceitec.cz/

    Poznámky

    Recommended literature:

    John, S., Olas, J. J. & Roeber, B. M. Regulation of alternative splicing in response to temperature variation in plants. J Exp Bot erab232 (2021) doi:10.1093/jxb/erab232.

    Kulichová, K. et al. PRP8A and PRP8B spliceosome subunits act coordinately to control pollen tube attraction in Arabidopsis thaliana. Development (Cambridge, England) 147, dev186742 (2020).

    Mácová, K. et al. Effects of long-term high-temperature stress on reproductive growth and seed development in development in Brassica napus. Biorxiv 2021.03.11.434971 (2021) doi:10.1101/2021.03.11.434971.

    Robert, H. S. et al. Local auxin sources orient the apical-basal axis in Arabidopsis embryos. Current Biology 23, 2506–2512 (2013).

    Školitel

    Helene Robert Boisivon, Ph.D.

    Long non-coding RNAs (lncRNAs) in the pathogenesis of mature B cell malignancies
    Školitel: doc. MUDr. Mgr. Marek Mráz, Ph.D.

    We are looking for a motivated PhD student that would like to work on the following project funded by the ERC (European Research Council) Starting grant. It has been shown that short non-coding RNAs significantly contribute the onset, progression, and therapy resistance in multiple B cell leukemias and lymphomas. We have recently described the role of miRNAs in microenvironmental interactions and aggressiveness of chronic lymphocytic leukemia and follicular lymphoma (Sharma et al…Mraz, Blood, 2021; Musilova et al…Mraz, Blood, 2018; Cerna et al…Mraz, Leukemia, 2019). However, the role of long non-coding RNAs in the pathogenesis of these diseases remains completely unknown.

    In this project, the student will decipher how lncRNAs regulated BCR signaling and microenvironmental interactions in B cell malignancies. We are mainly interested in chronic lymphocytic leukaemia (CLL) and follicular lymphoma (FL). CLL is the most common leukemia in adults and FL is the most common indolent non-Hodgkin lymphoma. The clinical course of CLL/FL patients can be surprisingly variable (survival from months to decades), and both diseases still remain incurable. The course of the diseases is characterized by repeated relapses leading to the evolution of resistant disease or to the high-grade transformation to a more aggressive diffuse large B-cell lymphoma/Richter. This is associated with a poor prognosis and a high risk of early death. Number of studies showed that multiple genetic lesions are associated with CLL/FL aggressiveness or transformation; however, precise molecular mechanisms underlying these processes are largely unclear. The project aims to reveal the molecular mechanisms involving lncRNAs and/or miRNAs responsible for CLL/FL aggressiveness, especially activation of BCR signaling and B-T cell interactions. The primary samples will be analyzed on the level of protein-coding as well as non-coding genes (NGS with Illumina, preliminary data available). This will be followed by searching for the function of lncRNAs using CRISPR interference, mouse models, and molecular biology technics. This will help to better understand the disease biology and possibly to identify novel molecular targets that could be used therapeutically.

    Requirements on candidates:
  • Motivated smart people that have the "drive" to work independently, but also willing to learn from other people in the lab and collaborate.
  • Candidates should have a master's degree in Molecular biology, Biochemistry, or similar field and have deep interest in molecular biology and cancer cell biology.
  • PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor or/and fill in the registration form on the web page of the CEITEC PhD School (link below).

    MORE INFORMATION:

    http://ls-phd.ceitec.cz/

    https://www.ceitec.eu/microenvironment-of-immune-cells/rg115

    Poznámky

    Recommended literature:

    Sharma et al. …Mraz. miR-29 Modulates CD40 Signaling in Chronic Lymphocytic Leukemia by Targeting TRAF4: an Axis Affected by BCR inhibitors. Blood 2021. https://pubmed.ncbi.nlm.nih.gov/33171493/.

    Musilova et al. …Mraz. miR-150 downregulation contributes to the high-grade transformation of follicular lymphoma by upregulating FOXP1 levels . BLOOD. 2018 NOV 29;132(22):2389-2400. https://pubmed.ncbi.nlm.nih.gov/33786575/.

    Musilova K, Mraz M. MicroRNAs in B-cell lymphomas: how a complex biology gets more complex. Leukemia. 2015 May;29(5):1004-17.

    Zeni and Mraz LncRNAs in adaptive immunity: role in physiological and pathological conditions. RNA Biol. 2021 May;18(5):619-632. https://pubmed.ncbi.nlm.nih.gov/33094664/

    Školitel

    doc. MUDr. Mgr. Marek Mráz, Ph.D.

    Microenvironment models and their use to study agressivness and targeted therapy in B cell malignancies
    Školitel: doc. MUDr. Mgr. Marek Mráz, Ph.D.

    Chronic lymphocytic leukemia (CLL) cells and indolent lymphomas are known to be dependent on diverse microenvironmental stimuli providing them signals for survival, development, proliferation, and therapy resistance. It is known that CLL cells undergo apoptosis after cultivation in vitro, and therefore it is necessary to use models of CLL microenvironment to culture CLL cells long-term and/or to study their proliferation. Several in vitro and in vivo models meet some of the characteristics of the natural microenvironment based on the coculture of malignant cells with T-lymphocytes or stromal cell lines as supportive cell, but they also have specific limitations.

    The aim of this research is to develop and use models mimicking lymphoid microenvironment to study mechanisms leading to aggressiveness in B cell malignancies and/or novel therapeutic options, e.g. drugs targeting CLL proliferation, development of resistance in long-term culture or combinatory approaches, which cannot be analyzed in experiments based on the conventional culture of CLL/lymphoma primary cells. This project will utilize models developed in the laboratory and will further optimize and modify them. The biology of CLL and responses to targeted treatment will be interrogated using the developed models. The student will utilize various functional assays, Cripr editing, RNA sequencing, genome editing, drug screening etc., with the use of primary patient’s samples and cell lines. The research might bring new insights into the microenvironmental dependencies and development of resistance to targeted therapy

    Requirements on candidates:
  • Motivated smart people that have the "drive" to work independently but are also willing to learn from other people in the lab and collaborate.
  • Candidates should have a master's degree in Molecular biology, Biochemistry, or a similar field and have a deep interest in molecular biology and cancer cell biology.
  • PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor or/and fill in the registration form on the web page of the CEITEC PhD School (link below).

    MORE INFORMATION:

    http://ls-phd.ceitec.cz/

    https://www.ceitec.eu/microenvironment-of-immune-cells/rg115

    Poznámky

    Recommended literature:

    Hoferkova E, Kadakova S, Mraz M. In Vitro and In Vivo Models of CLL-T Cell Interactions: Implications for Drug tetsing.Cancers (Basel). 2022 Jun 23;14(13):3087.

    Sharma et al. …Mraz. miR-29 Modulates CD40 Signaling in Chronic Lymphocytic Leukemia by Targeting TRAF4: an Axis Affected by BCR inhibitors. Blood 2021. https://pubmed.ncbi.nlm.nih.gov/33171493/

    Seda V. et al….Mraz. FoxO1-GAB1 Axis Regulates Homing Capacity and Tonic AKT Activity in Chronic Lymphocytic Leukemia. Blood, 2021, https://doi.org/10.1182/blood.2020008101.

    Kipps et al. Chronic lymphocytic leukaemia. Nat Rev 2017 https://pubmed.ncbi.nlm.nih.gov/28102226/.

    Seda V, Mraz M. B-cell receptor signalling and its crosstalk with other pathways in normal and malignant cells. Eur J Haematol. 2015 Mar;94(3):193-205. doi: 10.1111/ejh.12427. Epub 2014 Sep 13. PMID: 25080849 Review.

    Školitel

    doc. MUDr. Mgr. Marek Mráz, Ph.D.

    Phage infection of biofilm
    Školitel: doc. Mgr. Pavel Plevka, Ph.D.

    In 2017, the World Health Organization declared Staphylococcus aureus to be an antibiotic-resistant pathogen for which new therapeutics are urgently needed. Upon infection, S. aureus forms biofilms that can only be treated by the long-term application of several antibiotics in high doses or the surgical removal of the infected tissues. An alternative approach, phage therapy, has not been approved for clinical use, because the effects of phage infection on a biofilm are not sufficiently characterized. The student will study the dynamics of the propagation of a phage in a S. aureus biofilm and molecular details of its replication in a cell. He/she will determine how sub-populations of metabolically dormant or phage-resistant cells in a biofilm provide herd immunity against phage infection. In addition, he/she will use focused ion beam milling together with cryo-electron microscopy and tomography to determine high-resolution structures of previously uncharacterized phage replication and assembly intermediates in S. aureus cells.

    Requirements on candidates:

    Ideal candidate should have background in one of the following: molecular biology, biochemistry, physical chemistry, structural biology or informatics.

    PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor or/and fill in the registration form on the web page of the CEITEC PhD School (link below).

    MORE INFORMATION:

    http://ls-phd.ceitec.cz/

    https://plevkalab.ceitec.cz/

    Poznámky

    Recommended literature:

    Rigort et al., Focused ion beam micromachining of eukaryotic cells for cryoelectron tomography. Proc Natl Acad Sci U S A 109, 4449-4454 (2012).

    N. Cerca, R. Oliveira, J. Azeredo, Susceptibility of Staphylococcus epidermidis planktonic cells and biofilms to the lytic action of staphylococcus bacteriophage K. Lett Appl Microbiol 45, 313-317 (2007)

    M. Jemielita, M. J. Taormina, A. Delaurier, C. B. Kimmel, R. Parthasarathy, Comparing phototoxicity during the development of a zebrafish craniofacial bone using confocal and light sheet fluorescence microscopy techniques. J Biophotonics 6, 920-928 (2013).

    J. Girstmair et al., Light-sheet microscopy for everyone? Experience of building an OpenSPIM to study flatworm development. BMC Dev Biol 16, 22 (2016).

    E. J. Novacek et al., Structure and genome release of Twort-like Myoviridae phage with a double-layered baseplate. Proc Natl Acad Sci U S A 113, 9351-9356 (2016).

    Školitel

    doc. Mgr. Pavel Plevka, Ph.D.

    Restoring antiviral properties of mammalian Dicer
    Školitel: prof. Mgr. Richard Štefl, Ph.D.

    Dicer is an RNA-cutting enzyme, which is essential for regulation of gene activities in cells. The way Dicer cuts and trims RNA and how this affects gene silencing and antiviral immunity in lower organisms is well known. It combines two enzymatic activities, the helicase activity that is responsible for feeding RNA and the nuclease activity that is responsible for cutting it. The first function, feeding RNA into the enzyme, has altered during evolution despite conservation of the helicase catalytic center, with far-reaching consequences, such as the loss of Dicer’s antiviral properties. Our preliminary structural and functional work suggested that during evolution of vertebrates, the helicase domain of Dicer became locked in a specific position in which Dicer favours processing microRNAs and is unable to cleave viral RNA. In this project, we will find a strategy how to unlock the helicase domain to re-activate the ancestral antiviral activity of Dicer. This project will provide previously unexploited opportunities for design of a new defence mechanism against RNA viruses in humans.

    PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor or/and fill in the registration form on the web page of the CEITEC PhD School (link below).

    MORE INFORMATION:

    http://ls-phd.ceitec.cz/

    https://stefl-lab.ceitec.cz/

    Poznámky

    Recommended literature:

    Yamaguchi, S., Naganuma, M., Nishizawa, T. et al. Structure of the Dicer-2–R2D2 heterodimer bound to a small RNA duplex. Nature 607, 393–398 (2022). https://doi.org/10.1038/s41586-022-04790-2.

    Su, S., Wang, J., Deng, T. et al. Structural insights into dsRNA processing by DrosophilaDicer-2–Loqs-PD. Nature 607, 399–406 (2022). https://doi.org/10.1038/s41586-022-04911-x.

    Školitel

    prof. Mgr. Richard Štefl, Ph.D.

    Structural studies of various states of direct and bridged transcription-translation coupling in vitro and in vivo
    Školitel: Mgr. Gabriel Demo, Ph.D.

    Recent 30S subunit-RNA polymerase (RNAP) and expressome structures may represent interactions that occur at different steps of translation, e.g., during initiation and elongation. The aim is to structurally define the step-wise states of bacterial transcription-translation coupling and to determine whether accessory transcription factors or other proteins that link transcription and translation help to relocate RNAP on the ribosome - e.g., from its position in the 30S-RNAP structure to its position in the expressome structure.

    Single particle cryo-electron microscopy (cryo-EM) will be used to visualize transcription-translation coupling in vitro. Cryo-EM particle images from heterogeneous samples (in vitro reconstituted) will be classified into structurally homogeneous subsets by maximum-likelihood (ML) analyses. Packages such as Frealign and RELION with incorporated ML principles and extensive 3D-classification procedures, will be used to resolve conformational heterogeneity.

    Free 30S and 50S subunits mix with the nucleoid where they initiate cotranscriptional translation. Cellular co-localization of ribosomal subunits with RNAP protects the nascent mRNA and prevents undesirable backtracking of RNAP. The aim is to determine how is the coupling initiated within the nucleoid space and if the pioneer round of translation occurs within or near nucleoid space before formation of polysomes that segregate from the nucleoid.

    The RNAP-ribosome complexes will be visualized in situ at sub-nanometer resolution using cryo-electron tomography and sub-tomographic averaging of 3D volumes. E. coli cells will be flash-frozen directly onto EM grids allowing cellular structures to be studied in their near native states. Ultra-thin sections will be prepared directly on the EM grid in the electron microscope by focused ion beam milling.

    These studies can provide the insight on how translating ribosomes preserve genome integrity by preventing RNAP from backtracking or pausing. This combined approach can convincingly show in vivo the transcriptional-translational apparatus in action with all players involved in the coupling mechanism.

    Requirements on candidates:

    We are seeking a PhD. candidate who was trained in structural biology, mainly single particle cryo-EM or cryo-electron tomography (cryo-ET), and is a motivated person with collaborative mind set. The candidate should to be able to purify the components for structural studies of transcription-translation coupling.

    PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor or/and fill in the registration form on the web page of the CEITEC PhD School (link below).

    MORE INFORMATION:

    http://ls-phd.ceitec.cz/

    https://www.ceitec.eu/structural-biology-of-coupled-transcription-translation/rg352

    Poznámky

    Recommended literature:

    R. Kohler et al., Architecture of a transcribing-translating expressome. Science 356, 194-197 (2017).

    G. Demo et al., Structure of RNA polymerase bound to ribosomal 30S subunit. eLife 6, (2017).

    M. W. Webster et al., Structural basis of transcription-translation coupling and collision in bacteria. Science 369, 1355-1359 (2020).

    C. Wang et al., Structural basis of transcription-translation coupling. Science 369, 1359-1365 (2020).

    F. J. O'Reilly et al., In-cell architecture of an actively transcribing-translating expressome. Science 369, 554-557 (2020).

    Školitel

    Mgr. Gabriel Demo, Ph.D.

    Structural study of enterovirus replication in situ
    Školitel: doc. Mgr. Pavel Plevka, Ph.D.

    Diseases caused by enteroviruses include upper and lower respiratory tract infections, gastroenteritis, hand-foot-and-mouth-disease, and life-threatening meningoencephalitis. Rhinoviruses are responsible for 40% of common cold cases, which result in a yearly cost of tens of billions of US$ in treatments and lost working hours worldwide. The student will study the replication cycle of enteroviruses in situ by a combination of focused ion beam milling (FIBM) and cryo-electron tomography (cryoET). He/she will investigate the changes in intra-cellular organization induced by enterovirus infection, and the assembly of progeny virions. To facilitate the structural studies he/she will utilize patterned grids for electron microscopy to enable the automation of the FIBM of lamellas from tissue culture cells and the preparation of columnal sample geometry to increase the completeness of recordable cryo-ET data beyond the limit imposed by commonly used slab-shaped samples.

    Requirements on candidates:

    Ideal candidate should have background in one of the following: molecular biology, biochemistry, physical chemistry, structural biology or informatics.

    PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor or/and fill in the registration form on the web page of the CEITEC PhD School (link below).

    MORE INFORMATION:

    http://ls-phd.ceitec.cz/

    https://plevkalab.ceitec.cz/

    Poznámky

    Recommended literature:

    Palmenberg AC, et al. (2009) Sequencing and analyses of all known human rhinovirus genomes reveal structure and evolution. Science 324(5923):55-59.

    Fendrick AM, Monto AS, Nightengale B, & Sarnes M (2003) The economic burden of non-influenza- related viral respiratory tract infection in the United States. Archives of internal medicine 163(4):487-494.

    C. Tuthill TJ, Groppelli E, Hogle JM, & Rowlands DJ (2010) Picornaviruses. Curr Top Microbiol Immunol 343:43-89.

    Schaffer M, et al. (2017) Optimized cryo-focused ion beam sample preparation aimed at in situ.

    Structural studies of membrane proteins. J Struct Biol 197(2):73-82.

    Ren J, et al. (2013) Picornavirus uncoating intermediate captured in atomic detail. Nature communications 4:1929.

    Školitel

    doc. Mgr. Pavel Plevka, Ph.D.

    Structure of parallel forms of nucleic acids: NMR spectroscopy and molecular modeling
    Školitel: prof. RNDr. Radek Marek, Ph.D.

    The project is focused on detailed structural characterization of short purine oligonucleotides clipped by proper sequential motifs that induce parallel orientation of DNA strands. For this purpose, NMR experiments combined with MD simulations will be employed. The effect of modifications of selected nucleotides on the structural properties of designed models will be investigated to gain deeper understanding of key interactions that contribute to the folding of such systems.

    Requirements on candidates:

    Structural chemistry or biology, advanced NMR spectroscopy, computational chemistry.

    PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor or/and fill in the registration form on the web page of the CEITEC PhD School (link below).

    MORE INFORMATION:

    http://ls-phd.ceitec.cz/

    https://www.ceitec.eu/structure-of-biosystems-and-molecular-materials/rg108/tab?tabId=22

    Poznámky

    Recommended literature:

    Aleš NOVOTNÝ, Jan NOVOTNÝ, Iva KEJNOVSKÁ, Michaela VORLÍČKOVÁ, Radovan FIALA and Radek MAREK. Revealing structural peculiarities of homopurine GA repetition stuck by i-motif clip. Nucleic Acids Research, 2021, 49, 11425. doi:10.1093/nar/gkab915.

    Školitel

    prof. RNDr. Radek Marek, Ph.D.

    Tau conformational changes induced by phosphorylation, truncation, and 14-3-3 proteins relevant in neurodegenerative diseases
    Školitel: doc. RNDr. Mgr. Jozef Hritz, Ph.D.

    The main neuropathological signs of Alzheimer’s disease are associated with the fibrillization of tau protein into neurofibrillary tangles. Studying how different factors influence the formation of protein fibrils is the key to understanding these neurodegenerative processes. The main aim of this PhD project will be the characterization of conformational changes in the formation of tau fibrils due to their truncations, phosphorylation, and interaction with 14-3-3 proteins. An interdisciplinary approach combining biomolecular NMR, biophysical interaction techniques, and computational methods will be applied. The described activities are part of international research projects allowing us to spend part of PhD study in the groups of our collaborators in Europe or North and South America and to learn specific research techniques, there.

    Requirements on candidates:

    preferable candidate’s background in biophysics, biochemistry, structural or molecular biology.

    PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor or/and fill in the registration form on the web page of the CEITEC PhD School (link below).

    MORE INFORMATION:

    http://ls-phd.ceitec.cz/

    https://www.ceitec.eu/protein-structure-and-dynamics/rg110/tab?tabId=21

    Poznámky

    Recommended literature:

    Trosanova Z., Lousa P., Kozelekova A., Brom T., Gasparik N., Tungli J., Weisova V., Zupa E., Zoldak G., Hritz J.*: Quantitation of human 14-3-3zéta dimerization and the effect of phosphorylation on dimer-monomer ekvilibria. J. Mol. Biol. 2022, 434, 167479

    Kitoka K., Skrabana R., Gašparik N., Hritz J., Jaudzems K. NMR Studies of Tau Protein in Tauopathies. Front. Mol. Biosci. 2021, 8:761227.

    Zapletal, V.; Mládek, A.; Melková, K.; Louša, P.; Nomilner, E.; Jaseňáková, Z.; Kubáň, V.; Makovická, M.; Laníková, A.; Žídek L.; Hritz, J.* Choice of force field for proteins containing structured and intrinsically disordered regions. Biophys. J. 2020, 118, 1621 – 1633.

    Louša, P.; Nedozrálová, H.; Župa, E.; Nováček, J.; Hritz, J.*: Phosphorylation of the regulatory domain of human tyrosine hydroxylase 1 monitored using nonuniformly sampled NMR. Biophys. Chem. 2017, 223, 25-29.

    Jansen S., Melková K., Trošanová Z., Hanáková K., Zachrdla M., Nováček J., Župa E., Zdráhal Z., Hritz J.*, Žídek L.*: Quantitative Mapping of MAP2c Phosphorylation and 14-3-3zéta Binding Sites Reveals Key Differences Between MAP2c and Tau. J. Biol. Chem. 2017, 292, 6715-6727.

    Školitel

    doc. RNDr. Mgr. Jozef Hritz, Ph.D.

    Terminal RNA modifications in gene expression and viral infection
    Školitel: prof. Mgr. Štěpánka Vaňáčová, Ph.D.

    Posttranscriptional RNA modifications possess key roles in diverse pathways in humans, including development, disease and infections. This PhD project will focus on the machines and role of terminal modifications of coding and noncoding RNAs. They can affect mRNA metabolism and protein synthesis by direct mRNA modifications or via tailing of regulatory noncoding RNAs (ncRNAs). The topic is a follow up of our studies of RNA processing and surveillance mechanisms in human cells mediated by terminal uridylyltransferases (TUTases) and terminal nucleotide transferases (TENTS). You will address the question of regulators of this pathway and its impact in viral infections.

    The student will master diverse methodologies, such as human cell culture manipulations (cultivation, RNAi, CRISPR/Cas9, etc.), recombinant DNA preparation, protein expression and purification, high-throughput analyses and enzymatic assays.

    She/he will have the opportunity to present the results at prestigious international conferences. Moreover, this project will involve collaboration with other leading researches in European institutes.

    Requirements on candidates:

    The specification of the candidate's expected background in a case of importance Prospective student should ideally have done master degree in molecular biology/biochemistry and have a laboratory experience in nucleic acids and/or protein purification and analyses. Experience with coding in R and statistics is a big plus. The most highly valued feature however is excitement and curiosity for science and strong drive in tackling important biological questions.

    PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor and phd@ceitec.muni.cz

    MORE INFORMATION:

    http://ls-phd.ceitec.cz/

    https://www.ceitec.eu/rna-quality-control/rg55/tab?tabId=5

    Školitel

    prof. Mgr. Štěpánka Vaňáčová, Ph.D.

    Školitelé

    Studijní program nemá evidovány žádné školitele.

    Informace o studiu

    Zajišťuje Přírodovědecká fakulta
    Typ studia doktorský
    Forma prezenční ano
    kombinovaná ano
    distanční ne
    Možnosti studia jednooborově ano
    jednooborově se specializací ne
    v kombinaci s jiným programem ne
    Doba studia 4 roky
    Vyučovací jazyk angličtina
    Oborová rada a oborové komise
    Poplatky za studium
    Studium v cizích jazycích je zpoplatněné, platba je za akademický rok
    3 000 EUR
    Více informací

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