Vědy o živé přírodě

Annotation: 
 The aim of the project is to develop computational approaches and protocols for paramagnetic NMR spectroscopy. This includes density functional theory methods and multireference approaches for the calculation and analysis of EPR parameters (g-tensor, zero-field splitting, hyperfine coupling) and NMR shielding. The protocols will be developed and tested using model systems of metallodrugs and MRI contrast agents, and in later stages will be applied to selected metalloenzymes. Theoretical methods could be combined with molecular dynamics simulations and experimental NMR spectroscopy.

Requirements for candidate:
MSc degree in theoretical or physical chemistry, chemical physics, or related disciplines
Experience in computational chemistry

 PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website (link).
More information:
https://www.ceitec.eu/admission-step-by-step/t11340

Recommended literature:
Jan Novotný, Stanislav Komorovsky, Radek Marek. Paramagnetic Effects in NMR Spectroscopy of Transition-Metal Complexes: Principles and Chemical Concepts. Accounts of Chemical Research, 2024, 57, 1467-1477. doi: 10.1021/acs.accounts.3c00786.
 
Jan Novotný, Martin Sojka, Stanislav Komorovsky, Marek Nečas, Radek Marek. Interpreting the paramagnetic NMR spectra of potential Ru(III) metallodrugs: Synergy between experiment and relativistic DFT calculations. Journal of the American Chemical Society, 2016, 138, 8432-8445. doi: 10.1021/jacs.6b02749.
 
Anagha Sasikumar, Jan Novotný, Jan Chyba, Libor Kobera, Radek Marek. Supramolecular covalency of halogen bonds revealed by NMR contact shifts in paramagnetic cocrystals. Chemical Science, 2025, 16, online. doi: 10.1039/D5SC05769H.
 
Jan Novotný, Jan Chyba, Anna Hruzíková, Petra Pikulová, Aliaksandra Kursit, Michal Knor, Katerina Marková, Jaromír Marek, Pia Jurček, Ondrej Jurček, Radek Marek. Flipping hosts in hyperfine fields of paramagnetic guests. Cell Reports Physical Science, 2023, 4, 101461. doi: 10.1016/j.xcrp.2023.101461.

Školitel

prof. RNDr. Radek Marek, Ph.D.

Annotation: 
Small RNAs are master regulators of gene expression in animals and plants. They guide Argonaute proteins to target RNAs, forming effector complexes that execute RNA silencing - an essential process for cellular homeostasis, development, and defense. Despite decades of research, the molecular principles governing Argonaute activation, guide-RNA loading, and strand selection remain poorly understood.
This PhD project aims to decipher the molecular mechanism of Argonaute loading using state-of-the-art electron cryomicroscopy (cryo-EM) combined with complementary biochemical and functional analyses. Building on our recent discoveries and concepts, we propose that two distinct loading pathways operate in mammals: one orchestrated by Dicer and another by HSP90–co-chaperone systems, both relying on negatively charged intrinsically disordered regions (IDRs) that have been largely overlooked in previous structural studies.
The student will determine high-resolution cryo-EM structures of key intermediates in these pathways-including Dicer-Argonaute-RNA and HSP90-co-chaperone-Argonaute-RNA assemblies-to visualize how conformational changes enable RNA transfer and strand selection.
By resolving this long-standing mechanistic puzzle, the project will define the molecular principles of Argonaute loading, shed light on the evolution and regulation of RNA silencing, and provide structural insights into the pathogenic mechanisms underlying AGO-related developmental disorders (AGO Syndrome).
Requirements for candidate:
Biochemistry/molecular biology/structural biology

PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website (link).
More information:
https://www.ceitec.eu/admission-step-by-step/t11340

Recommended literature:
1) Dicer structure and function: conserved and evolving features. Zapletal D, Kubicek, K, Svoboda P, Stefl R EMBO Reports (2023) 24:e57215 doi:10.15252/embr.202357215
2) microRNAs in action: biogenesis, function and regulation. Shang R, Lee S, Senavirathne G, Lai EC. Nat Rev Genet. 2023 doi:10.1038/s41576-023-00611-y.

Poznámky

Recommended literature:

1) Dicer structure and function: conserved and evolving features. Zapletal D, Kubicek, K, Svoboda P, Stefl R EMBO Reports (2023) 24:e57215 doi:10.15252/embr.202357215

2) microRNAs in action: biogenesis, function and regulation. Shang R, Lee S, Senavirathne G, Lai EC. Nat Rev Genet. 2023 doi:10.1038/s41576-023-00611-y.

Školitel

prof. Mgr. Richard Štefl, Ph.D.

Annotation: 

Most approved drugs act on cell-surface targets or enter cells passively. For compounds with poor solubility or low membrane permeability, encapsulation in liposomes is a proven strategy to improve these properties. However, encapsulated drugs often remain trapped within the liposome, limiting their bioavailability and therapeutic efficacy. This project will investigate coiled-coil peptides as a scaffold for assemblies that enable controlled membrane fusion and intracellular cargo delivery. Using a combination of coarse-grained molecular dynamics simulations with the Martini force field and complementary biophysical approaches, we will elucidate the peptide features and molecular mechanisms that enable efficient membrane fusion. The outcomes of this research will advance our understanding of peptide-mediated membrane fusion and provide a framework for the rational design of delivery systems for biotechnological and therapeutic applications.
Requirements for candidate:

• MSc in computational biophysics/chemistry/physics and related fields
• Experience with Molecular Dynamics using coarse grained or atomistic models
• Advantage is experience with simulations of disordered proteins/polymers and membranes
• Excellent track record
• Good English language – spoken and written
• Motivated person with collaborative mind set

PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website (link).
More information:
https://www.ceitec.eu/admission-step-by-step/t11340
 

Recommended literature:

Blasco S.; Sukeník, L.; Vácha, R.: Nanoparticle induced fusion of lipid membranes. Nanoscale 2024, 16, 10221-10229, doi: 10.1039/D4NR00591K

Risselada H.J.; Bubnis G.; Grubmüller H.: Expansion of the fusion stalk and its implication for biological membrane fusion. Proc. Natl. Acad. Sci. USA 2014, 111, 30, 11043-11048, doi: 10.1073/pnas.1323221111

Jahn R.; Cafiso D.C.;  Tamm L.K.: Mechanisms of SNARE proteins in membrane fusion. Nat. Rev. Mol. Cell. Bio.l 2024, 25, 101–118, doi: 10.1038/s41580-023-00668-x

Wang L.; Wang G.; Mao W.; et al. Bioinspired engineering of fusogen and targeting moiety equipped nanovesicles. Nat Commun 2023, 14, 3366, doi: 10.1038/s41467-023-39181-2

Školitel

prof. RNDr. Robert Vácha, PhD.

Annotation:
To initiate infection, viruses deliver their genomes into host cells. Whereas enveloped viruses fuse their membrane with that of a cell, the cell entry mechanisms employed by non-enveloped viruses are less understood. Recently, it has been shown that endosome rupture enables cell entry of picornaviruses. The student will analyze the putative role of endosome rupture in the cell entry of adenoviruses, polyomaviruses, and parvoviruses. He/She will employ cryo-electron microscopy and tomography to visualize the early stages of cell virus entry in peripheral parts of cells that can be imaged using transmission electron microscopy. The student will analyze changes in the structure of virus particles and endosome membranes that enable the viruses to deliver their genomes into the cytoplasm.
Requirements for candidate:
The prospective student should be interested in learning cryo-EM and structure determination approaches. Previous experience with molecular biology, programming, scripting, and data analyses is a plus.


PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website (link).
More information:
https://www.ceitec.eu/admission-step-by-step/t11340
Recommended literature:
Virus entry by endocytosis. Mercer J, Schelhaas M, Helenius A. Annu Rev Biochem. 2010;79:803-33. doi: 10.1146/annurev-biochem-060208-104626. PMID: 20196649
 
Adenovirus Entry: From Infection to Immunity. Greber UF, Flatt JW. Annu Rev Virol. 2019 Sep 29;6(1):177-197. doi: 10.1146/annurev-virology-092818-015550. Epub 2019 Jul 5. PMID: 31283442
 
Sending mixed signals: polyomavirus entry and trafficking. Mayberry CL, Bond AC, Wilczek MP, Mehmood K, Maginnis MS. Curr Opin Virol. 2021 Apr;47:95-105. doi: 10.1016/j.coviro.2021.02.004. Epub 2021 Mar 6. PMID: 33690104
 
Parvoviral host range and cell entry mechanisms. Cotmore SF, Tattersall P. Adv Virus Res. 2007;70:183-232. doi: 10.1016/S0065-3527(07)70005-2. PMID: 17765706

Školitel

doc. Mgr. Pavel Plevka, Ph.D.

Annotation:
The project is focused on detailed structural characterization of short oligonucleotides in noncanonical forms clipped together by proper sequential motifs. 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 a deeper understanding of key interactions that contribute to the system folding and stability.

Requirements for candidate:
Structural chemistry or biology, advanced NMR spectroscopy, computational chemistry

PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website (link).
More information:
https://www.ceitec.eu/admission-step-by-step/t11340
 

Recommended literature:

Aleš Novotný, Jan Novotný, Iva Kejnovská, Michaela Vorlíčková, Radovan Fiala, 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.

Annotation:

With nearly 10 million lives claimed annually, cancer remains one of the leading causes of mortality worldwide, highlighting the urgent need for more effective treatments. One promising strategy involves mRNA-based cancer immunotherapy vaccines, which require a drug delivery system capable of reliably reaching the cytosol. Developing such delivery systems is challenging: they must ensure cytosolic delivery and therapeutic efficacy while maintaining safety, long-term stability, and compliance with scalable manufacturing standards -  including high mRNA loading efficiency and uniform particle size. Current lipidand polymer-based systems offer distinct advantages but integrating lessons from both may help develop more effective next-generation carriers. A major limitation remains the incomplete understanding of nanoparticle assembly and disassembly under diverse physiological conditions (e.g., extracellular fluids, endosomal compartments, cytosol). This project will use coarse-grained molecular simulations, complemented by in-house experimental validation, to gain molecular insights in the controlled system assembly and disassembly. Our goal is to guide the rational design of improved mRNA delivery systems to advance the efficacy of cancer immunotherapy.

Requirements for candidate:
 
Msc in computational biophysics/chemistry/physics and related fields
Experience with Molecular Dynamics using coarse grained or atomistic models
Advantage is experience with simulations of disordered proteins/polymers and membranes
Excellent track record
Good English language – spoken and written
Motivated person with collaborative mind set

PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website (link).
More information:
https://www.ceitec.eu/admission-step-by-step/t11340


Recommended literature:

Paunovska K., et al.: Nat Rev Genet 2022, 23, 265–280, Doi: 10.1038/s41576-021-00439-4
Hou X., et al.: Nat Rev Mater 2021, 6, 1078–1094, Doi: 10.1038/s41578-021-00358-0
Yasuda I. et al.: J. Chem. Theory Comput. 2025, 21, 5, 2766–2779, Doi: 10.1021/acs.jctc.4c01646
Chew P.Y., et al.: Chem. Sci., 2023,14, 1820-1836, Doi: 10.1039/D2SC05873A

Školitel

prof. RNDr. Robert Vácha, PhD.

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 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 novel therapeutic options, e.g. drugs targeting CLL proliferation, development of resistance in long-term culture or combinatory approaches, which cannot be analysed in experiments based on conventional culture of CLL/lymphoma primary cells. This project will utilize models developed in the laboratory and will further optimize and modify them. We have recently developed a co-culture model that is allowing to induce robust proliferation of primary CLL cells, something that was virtually impossible for decades (Hoferkova et al, Leukemia, 2024). Using kinase inhibitors, the biology of CLL and responses to targeted treatment will be interrogated. The student will utilize various functional assays, 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 who 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.

More information: RG Microenvironment of Immune Cells

PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website (link).
More information:
https://www.ceitec.eu/admission-step-by-step/t11340
 

Poznámky

Recommended literature:

1. Hoferkova E, et al…. Mraz M. Stromal cells engineered to express T cell factors induce robust CLL cell proliferation in vitro and in PDX co-transplantations allowing the identification of RAF inhibitors as anti-proliferative drugs. Leukemia. 2024 Aug;38(8):1699-1711

2. Pavlasova G, et al…. Mraz M. Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by the CXCR4/SDF-1 axis. Blood. 2016 Sep 22;128(12):1609-13. doi: 10.1182/blood-2016-04-709519. Epub 2016 Aug 1. PMID: 27480113 Free PMC article

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

4. 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

prof. MUDr. Mgr. Marek Mráz, Ph.D.

Annotation: 
Co-translational quality control is triggered as a response to translational stalling events. Yet, different molecular mechanisms are employed for the recognition of these stalls and to trigger downstream rescue and quality control pathways. The use of collided ribosomes as a proxy for the recognition of translation problems in the cell is conserved from bacteria to humans. In eukaryotes, co-translational quality-control processes triggered by ribosome collisions accomplish several tasks and eventually trigger stress response signalling pathways. These tasks include the degradation of aberrant mRNAs, the degradation of potentially deleterious nascent peptides, the ribosomal subunit rescue and tRNA recycling. We mainly use structural analysis by cryo-EM to gain mechanistic understanding of these translational control events. To that end, we reconstitute macromolecular complexes involved in these processes in vitro or isolate them from cells.
The successful candidate will utilize a multidisciplinary approach to provide detailed mechanistic understanding of the critical human co-translational processes. He/she will utilize human cell cultures, protein expression and purification techniques and biochemistry methods to produce samples for cryogenic electron microscopy (cryo-EM). Comprehensive training in cryo-EM will be available to the successful candidate.

Requirements for candidate:
The ideal candidate should have background in either molecular biology, biochemistry or structural biology. Experience with human cell culture work, RNA biochemistry or protein expression and purification is a strong plus.

PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website (link).
More information:
https://www.ceitec.eu/admission-step-by-step/t11340

Recommended literature:
1. Filbeck, S., et al., Ribosome-associated quality-control mechanisms from bacteria to humans. Mol Cell, 2022. 82(8): p. 1451-1466.
2. Ikeuchi, K., et al., Collided ribosomes form a unique structural interface to induce Hel2-driven quality control pathways. EMBO J, 2019. 38(5).
3. Saito, K., et al., Ribosome collisions induce mRNA cleavage and ribosome rescue in bacteria. Nature, 2022. 603(7901): p. 503-508.
4. Narita, M., et al., A distinct mammalian disome collision interface harbors K63-linked polyubiquitination of uS10 to trigger hRQT-mediated subunit dissociation. Nat Commun, 2022. 13(1): p. 6411.
5. Wu, C.C., et al., Ribosome Collisions Trigger General Stress Responses to Regulate Cell Fate. Cell, 2020. 182(2): p. 404-416 e14.
 

Školitel

RNDr. Petr Těšina, Ph.D.

Annotation:
 
Tick-borne encephalitis virus (TBEV) is a medically significant flavivirus causing severe neurological disease in humans. Despite the availability of TBE vaccines, the number of TBE cases continues to rise, necessitating further research into the immune response to TBEV infection to enable the development of therapeutics. The student will use cryo-electron microscopy to determine the structures of antibody-TBEV complexes at near-atomic resolution, revealing binding modes and conformational changes to both the virus envelope proteins and antibodies. Using EMPEM approach the student will analyse polyclonal antibodies from human sera and compare their epitopes to those of functionally well-characterized  mabs with different neutralizing and/or enhancing properties.
Requirements for candidate:
The prospective student should be interested in learning cryo-EM and structure determination approaches. Previous experience with molecular biology, programming, scripting, and data analyses is a plus.
PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website (link).
More information:
https://www.ceitec.eu/admission-step-by-step/t11340
Recommended literature:
Torrents de la Peña A, Ward AB. Microfluidics combined with electron microscopy for rapid and high-throughput mapping of antibody-viral glycoprotein complexes. Sewall LM, de Paiva Froes Rocha R, Gibson G, Louie M, Xie Z, Bangaru S, Tran AS, Ozorowski G, Mohanty S, Beutler N, Rogers TF, Burton DR, Shaw AC, Batista FD, Chocarro Ruiz B, Nat Biomed Eng. 2025 Jun 3:10.1038/s41551-025-01411-x. doi: 10.1038/s41551-025-01411-x. Epub ahead of print. PMID: 40461656; PMCID: PMC12404239.
 
Fuzik T, Formanova P, Ruzek D, Yoshii K, Niedrig M, Plevka P. Structure of tick-borne encephalitis virus and its neutralization by a monoclonal antibody. Nat Commun. 2018;9(1):436. doi: 10.1038/s41467-018-02882-0.
 
The structure of immature tick-borne encephalitis virus supports the collapse model of flavivirus maturation.
Anastasina M, Füzik T, Domanska A, Pulkkinen LIA, Šmerdová L, Formanová PP, Straková P, Nováček J, Růžek D, Plevka P, Butcher SJ. Sci Adv. 2024 Jul 5;10(27):eadl1888. doi: 10.1126/sciadv.adl1888.
 
Kuhn RJ, Zhang W, Rossmann MG, Pletnev SV, Corver J, Lenches E, et al. Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell. 2002;108(5):717-25. doi: 10.1016/s0092-8674(02)00660-8.

Školitel

doc. Mgr. Pavel Plevka, Ph.D.

Annotation: 
 
CDK12 is a 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, and plays a role in cell cycle progression by regulating processivity of RNA Polymerase IIat core DNA replication genes. Apart from the C-terminal domain of RNA Polymerase II, other cellular substrates of CDK12 are not known. In this research, we propose using a screen in cells carrying an analogsensitive mutant of CDK12 to discover its novel cellular substrates. The substrates and their roles in normal and cancerous cells will be characterized by advanced techniques of molecular biology and biochemistry.

Requirements for candidate:
 
Background in molecular biology, biochemistry, or life sciences. Interest in bioinformatics and data analysis is desirable.
PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website (link).
More information:
https://www.ceitec.eu/admission-step-by-step/t11340

Recommended literature:
 
1. 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)
2. 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)
3. 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)
4. 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).

Školitel

Mgr. Dalibor Blažek, Ph.D.

Annotation: 
 
Protein-DNA interactions are critical in cellular processes and genetic instability-related conditions, particularly involving G-quadruplexes (G4) and their complementary C-rich sequences (i-Motif). Due to the composite viscoelastic environment in living cells, the polymorphism is highly complex, featuring dynamic conformational equilibrium between several folded and unfolded sub-populations driven by G4/i-Motif-binding proteins (Helicases, recruited proteins, transcription factors, etc.). Helicases are ubiquitous molecular motors involved in the homeostatic regulation of the folding/unfolding of these structures, thereby mediating replication, repair, transcription, and DNA damage response through protein barriers. Peptides from helicase motifs can be used to investigate atomistic details of G4-Helicase interactions and decipher structure-activity relations. The candidate will explore the folding and regulation of their rugged folding energy landscape of G-quadruplexes and i-Motifs in the presence of peptide fragments from the helicase motifs.
This project will utilize low and high-resolution orthogonal biophysical techniques (such as NMR, native mass spectrometry, and molecular dynamics) to investigate atomistic details of these interactions and conformational alterations. The results will shed light on the fundamental mechanisms of Helicase-Non-canonical nucleic acid interactions, which are essential for understanding G4/ i-Motif biology in fine-tuning gene expression and alleviating associated cellular dysfunctions. The design of peptide-based G4/i-Motif inhibitors can be used in (a) epigenetic-driven anticancer, neurological, or antiviral therapies by disrupting the overrepresentation of those forms, (b) non-invasive biomarkers to detect G4/i-Motif structures in biological samples (blood plasma) for disease diagnosis.

Requirements for candidate: Master's degree in Chemistry/Biochemistry/Biology/Biophysics

PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website (link).
More information:
https://www.ceitec.eu/admission-step-by-step/t11340

Recommended literature:

1. Tateishi-Karimata,H. and Sugimoto,N. (2021). Nucleic Acids Res., 49, 7839–7855.
2. 17. Sauer,M. and Paeschke,K. (2017. Biochem. Soc. Trans., 45, 1173–1182.
3. Mendoza,O., Bourdoncle,A., Boulé,J.-B., Brosh,R.M. and Mergny,J.-L. (2016). Nucleic Acids Res., 44, 1989–2006.
4. Chen,M.C., Tippana,R., Demeshkina,N.A., Murat,P., Balasubramanian,S., Myong,S. and Ferré-D'Amaré,A.R. (2018). Nature, 558, 465–469.
5. Heddi,B., Cheong,V.V., Martadinata,H. and Phan,A.T. (2015). Proc. Natl. Acad. Sci., 112, 9608–9613.

Školitel

doc. Mgr. Lukáš Trantírek, Ph.D.

Annotation: 

Cancer remains one of the leading causes of mortality worldwide, claiming nearly ten million lives each year. One promising treatment is cancer immunotherapy using mRNA encapsulated in lipid vesicles, which facilitate efficient drug transport into target cells. However, the delivery of mRNA into the cell remains a challenge due to limited endosomal escape. To overcome the endosomal escape barrier, this project aims to computationally design proteins that induce fusion between lipid vesicles and endosomes. Using mesoscopic simulations, we will identify the key structural features of proteins with a transmembrane domain that promote membrane fusion. These insights will inform the rational design of coiled-coil peptide sequences with said features and assess their capacity to induce membrane fusion using Martini coarse-grained simulations. This research will elucidate the molecular mechanism of protein-mediated membrane fusion, establishing a framework for the rational design of fusogenic proteins. The designed proteins will enable the development of lipid vesicles with increased endosomal escape efficiency, which has the potential to improve the intracellular delivery of mRNA. Collectively, these advances will contribute to the broader vision of developing clinically relevant platforms that expand the therapeutic potential of nucleic acid medicines and accelerate their translation into effective therapies.

Requirements for candidate:

• MSc in computational biophysics/chemistry/physics and related fields
• Experience with Molecular Dynamics using coarse grained or atomistic models
•  Advantage is experience with simulations of disordered proteins/polymers and membranes
• Excellent track record
• Good English language – spoken and written
• Motivated person with collaborative mind set

 PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website (link).
More information:
https://www.ceitec.eu/admission-step-by-step/t11340
 

Recommended literature:

Blasco S.; Sukeník, L.; Vácha, R.: Nanoparticle induced fusion of lipid membranes. Nanoscale 2024, 16, 10221-10229, doi: 10.1039/D4NR00591K

Risselada H.J.; Bubnis G.; Grubmüller H.: Expansion of the fusion stalk and its implication for biological membrane fusion. Proc. Natl. Acad. Sci. USA 2014, 111, 30, 11043-11048, doi: 10.1073/pnas.1323221111

Jahn R.; Cafiso D.C.;  Tamm L.K.: Mechanisms of SNARE proteins in membrane fusion. Nat. Rev. Mol. Cell. Bio.l 2024, 25, 101–118, doi: 10.1038/s41580-023-00668-x

Wang L.; Wang G.; Mao W.; et al. Bioinspired engineering of fusogen and targeting moiety equipped nanovesicles. Nat Commun 2023, 14, 3366, doi: 10.1038/s41467-023-39181-2

Školitel

prof. RNDr. Robert Vácha, PhD.

Annotation: 
In-cell NMR spectroscopy has emerged as a unique and powerful approach for probing biomolecular structure, dynamics, and interactions directly within living human cells under near-physiological conditions. It holds transformative potential for both basic biomedical research and pharmaceutical development, enabling direct analysis of drug-target engagement, binding affinities, and structural validation in the cellular context. However, current applications of in-cell NMR remain largely confined to asynchronous, 2D monocultures of immortalized or cancer-derived cell lines. This narrow experimental window limits both biological relevance and translational potential.
In our previous work, we successfully addressed key limitations of in-cell NMR by establishing two innovative strategies: (1) structural characterization in cell cycle–synchronized cells and (2) in-cell NMR within 3D human tissue spheroids. These efforts provided essential proof-of-principle for expanding the applicability of the technique to more complex biological systems.
Building on this foundation, the proposed project aims to take a critical step forward by developing and applying in-cell NMR spectroscopy in 3D human organ models derived from pluripotent stem cells. These models represent the current gold standard for replicating organ-level physiology in vitro, offering unprecedented opportunities to study molecular events within realistic tissue architecture and differentiation contexts. The PhD candidate will develop protocols for isotope labeling, sample handling, and NMR acquisition in stem cell-derived 3D tissues.

Requirements for candidate:

Master's degree in Molecular or Cellular Biology/ Biochemistry /Chemistry / Biophysics

Prior experience with organoid production, induced pluripotent stem cells (iPSCs), or protein NMR spectroscopy is considered an asset.

PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website (link).
More information:
https://www.ceitec.eu/admission-step-by-step/t11340

Recommended literature:
1: Theillet FX, Luchinat E. In-cell NMR: Why and how? Prog Nucl Magn Reson
Spectrosc. 2022 Oct-Dec;132-133:1-112.
2: Theillet FX. In-Cell Structural Biology by NMR: The Benefits of the Atomic
Scale. Chem Rev. 2022 May 25;122(10):9497-9570.
3: Luchinat E, Banci L. In-cell NMR: From target structure and dynamics to drug
screening. Curr Opin Struct Biol. 2022 Jun;74:102374.
4:  Rynes J, Istvankova E, Dzurov Krafcikova M, Luchinat E, Barbieri L, Banci L,
Kamarytova K, Loja T, Fafilek B, Rico-Llanos G, Krejci P, Macurek L, Foldynova-
Trantirkova S, Trantirek L. Protein structure and interactions elucidated with
in-cell NMR for different cell cycle phases and in 3D human tissue models.
Commun Biol. 2025 Feb 7;8(1):194.

Školitel

doc. Mgr. Lukáš Trantírek, Ph.D.

The project goal is to understand the molecular machinery that regulates the migration of malignant B cells between different niches such as lymphoid and bone marrow niche and peripheral blood. This is of great interests a general mechanism of how migration is regulated in cancer cells, but also especially in chronic lymphocytic leukemia (CLL), which is a disease dependent on the B cell recirculation between different compartments (reviewed in Seda and Mraz, 2015; Seda et al, 2021). In CLL, but also in other lymphomas, the malignant B cells permanently re-circulate from peripheral blood to lymph nodes and back, and blocking this recirculation can be used therapeutically since malignant B cells depend on signals in the immune microenvironment. However, the factors that regulate this are mostly unclear. The lab established several models for in vitro and in vivo studies of microenvironmental interactions and their interplay (Hoferkova et al, Leukemia, 2024; Pavlasova et al. Blood, 2016; Pavlasova et al. Leukemia, 2018; Musilova et al. Blood, 2018; Mraz et al. Blood, 2014; Cerna et al. Leukemia, 2019).
We have identified candidate molecules that might act as novel regulators of the B cell migration or the balance between homing and survival in peripheral blood. This will be further investigated by the PhD student using technics such as genome editing (CRISPR), RNA sequencing, use of primary samples, functional studies with various in vitro and in vivo mouse models. The research is also relevant for understanding resistance mechanisms to BCR inhibitors, pre-clinical development of novel drugs and their combinations (several patents submitted by the lab).

Requirements on candidates:

Motivated smart people who 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.

More information: RG Microenvironment of Immune Cells

PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website (link).
More information:
https://www.ceitec.eu/admission-step-by-step/t11340
 

Poznámky

Recommended literature:

1. Seda et al….Mraz FoxO1-GAB1 Axis Regulates Homing Capacity and Tonic AKT Activity in Chronic Lymphocytic Leukemia. Blood 2021 March (epub). https://pubmed.ncbi.nlm.nih.gov/33786575/

2. Pavlasova G, et al…. Mraz M. Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by the CXCR4/SDF-1 axis. Blood. 2016 Sep 22;128(12):1609-13. doi: 10.1182/blood-2016-04-709519. Epub 2016 Aug 1. PMID: 27480113 Free PMC article

3. 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

prof. MUDr. Mgr. Marek Mráz, Ph.D.

Annotation:
Despite decades of study, important aspects of phage replication cycles, such as the mechanism of genome delivery, initiation of head assembly, and genome packaging, are poorly understood. We propose to use cryo-electron microscopy and tomography to characterize replication intermediates of phage LE3 infecting Leptospira. The in situ data collection will be enabled by the dimensions of leptospira cells, which are 100 nm thin. Analysis of the infection intermediates will focus on genome delivery, initiation of head assembly, and genome packaging. These processes cannot be studied in vitro because of the challenges of preparing the corresponding complexes in functional form in sufficient amounts.
Requirements for candidate:
The prospective student should be interested in learning cryo-EM and structure determination approaches. Previous experience with molecular biology, programming, scripting, and data analyses is a plus.
PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website (link).
More information:
https://www.ceitec.eu/admission-step-by-step/t11340
Recommended literature:
Characterization of LE3 and LE4, the only lytic phages known to infect the spirochete Leptospira. Schiettekatte O, Vincent AT, Malosse C, Lechat P, Chamot-Rooke J, Veyrier FJ, Picardeau M, Bourhy P. Sci Rep. 2018 Aug 6;8(1):11781. doi: 10.1038/s41598-018-29983-6.
 
Molecular architecture of tailed double-stranded DNA phages. Fokine A, Rossmann MG. Bacteriophage. 2014 Jan 1;4(1):e28281. doi: 10.4161/bact.28281. Epub 2014 Feb 21. PMID: 24616838
 
A century of the phage: past, present and future. Salmond GP, Fineran PC. Nat Rev Microbiol. 2015 Dec;13(12):777-86. doi: 10.1038/nrmicro3564. Epub 2015 Nov 9. PMID: 26548913
 
Viral genome packaging machines: Structure and enzymology. Catalano CE, Morais MC. Enzymes. 2021;50:369-413. doi: 10.1016/bs.enz.2021.09.006. Epub 2021 Nov 10. PMID: 34861943
 
Casjens, S. R. (2011). The DNA-packaging nanomotor of tailed bacteriophages. Nature Reviews Microbiology, 9(9), 647–657. doi:10.1038/nrmicro2632

Školitel

doc. Mgr. Pavel Plevka, Ph.D.

Annotation: 
The PhD project is a continuation of previous studies of the research group, in collaboration with the Libor Krasny of Institute of Microbiology, Academy of Sciences of The Czech Academy of Sciences. Krasny’s lab discovered several proteins of Gram-positive bacteria that play so far little understood roles in transcription regulation. The goal of the project is to combine structural biology approaches to establish relation between structure, biophysical properties, and function of these proteins and other poorly understood bacterial transcription factors. The particular aims include maping of transient interactions of the delta subunit with the RNA polymerase core of Bacillus subtilis, interplay between delta subunit and sigma factors, interactions of a recently discovered transcription factor MoaB2 with mycobacterial sigma factors and RNA polymerases. Cryo-electron microscopy will be used as a major tool to study structures of the proteins in complexes with RNA polymerase. A particular attention will be paid to dynamics of the proteins, that often contain large disordered regions, where cryo-EM data will be combined with results of NMR spectroscopy. As alternative methods, FRET (and potentially EPR in collaboration with V. Laguta) using advanced labelling techniques will be used. The project should result in publications in respected journals with the student being the (shared) first author.

Requirements for candidate:
Strong background in biophysics and/or physical chemistry, experience with electron microscopy or NMR spectroscopy is an advantage.

PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website (link).
More information:
https://www.ceitec.eu/admission-step-by-step/t11340
Recommended literature:
 
Brezovská et al., J. Bacteriol. 2024, 122, 206
https://dx.doi.org/10.1128/jb.00066.24
Camacho-Zarco et al., Chem. Reviews. 2022, 122, 9331-9356
https://dx.doi.org/10.1021/acs.chemrev.1c01023
Kubáň et al., J. Am. Chem. Soc. 2019, 141, 16817-16828.
https://dx.doi.org/10.1021/jacs.9b07837

Školitel

prof. Mgr. Lukáš Žídek, Ph.D.

Annotation:
Tailed phages are a diverse group of viruses abundant in all econiches as revealed by recent metagenomic studies. In the past ten years a substantial effort has been made over an evolutionary sound classification of these viruses. However, due to rapid evolution, the phylogenetic signal, contained in the amino acid sequence of tailed phages, is eroded. As a result, current classification stays fragmented. On the other hand, protein folds remain conserved over greater evolutionary distances. Therefore, phylogenetic inference based on the structure of phage virion proteins may provide a deeper insight into their evolutionary history. Currently, the methods for structure-guided phylogeny are not well developed. The purpose of this project is to optimize the method for maximum likelihood phylogenetic inference on protein structure and use it to reveal new evolutionary connections within tailed phages. The work will involve general bioinformatics methods, including bash-scripting, database search tools, multiple sequence alignment tools and phylogenetic software. The candidate will gain extensive theoretical background and practical skills to work in the field of evolutionary biology.
Requirements for candidate:
The prospective student should be interested in learning techniques of structural phylogeny. Previous experience with molecular biology, programming, scripting, and data analyses is a plus.
PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website (link).
More information:
https://www.ceitec.eu/admission-step-by-step/t11340
Recommended literature:
Weinheimer AR, Ha AD, Aylward FO. Towards a unifying phylogenomic framework for tailed phages. PLoS Genet. 2025 Feb 5;21(2):e1011595. doi: 10.1371/journal.pgen.1011595. PMID: 39908317; PMCID: PMC11835377.
 
Mifsud JCO, Suchard MA, Holmes EC, Lemey P. Recent advances in the inference of deep viral evolutionary history. J Virol. 2025 Sep 23;99(9):e0029225. doi: 10.1128/jvi.00292-25. Epub 2025 Aug 22. PMID: 40844272; PMCID: PMC12456133.
 
Ng WM, Stelfox AJ, Bowden TA. Unraveling virus relationships by structure-based phylogenetic classification. Virus Evol. 2020 Feb 12;6(1):veaa003. doi: 10.1093/ve/veaa003. PMID: 32064119; PMCID: PMC7015158.
 
Moi D, Bernard C, Steinegger M, Nevers Y, Langleib M, Dessimoz C. Structural phylogenetics unravels the evolutionary diversification of communication systems in gram-positive bacteria and their viruses. Nat Struct Mol Biol. 2025 Oct 10. doi: 10.1038/s41594-025-01649-8. Epub ahead of print. PMID: 41073779.

Školitel

doc. Mgr. Pavel Plevka, Ph.D.

Annotation: 
CAR-T cells are genetically engineered T lymphocytes expressing chimeric antigen receptor (CAR), which reprograms them to specifically kill tumour cells. Despite their clear success in the therapy of some haematological malignancies, CAR-T cell therapy largely fails in other leukaemias like CLL or AML. One of the reasons is the dysfunction of patients T cells due to their functional exhaustion. Recently, it was shown that tumour cells can form thin membranous protrusions with their surrounding cells, among others with T cells. These protrusions are called tunnelling nanotubes (TNTs) and it was proposed that tumour cells are able to use these TNTs to steal mitochondria from their partners, incl. T cells, thereby weakening T cells and causing their dysfunction. We have discovered that these TNTs are indeed formed also between CLL cells and T cells and this results in the transport of mitochondria from T cells towards leukemic cells.
This PhD project will analyse the molecular mechanisms responsible for TNT formation and mitochondrial loss. We will perform genome-wide CRISPR/Cas9 screen and RNA-sequencing to identify factors required for mitochondrial exchange. Importantly, we will investigate approaches how to revert this phenomenon and how to enhance mitochondrial content within T cells in order to generate more potent CAR-T cells with boosted killing activity.
Requirements for candidate:

• Master degree in molecular biology, cell biology, biochemistry or related studies
• Practical experience with mammalian cell culture
• Knowledge of tumour cell biology is of advantage
• High motivation and enthusiasm to perform top-notch research

PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website (link).
More information:
https://www.ceitec.eu/admission-step-by-step/t11340
Recommended literature:

1. Sadelain, M., et al. (2013). "The basic principles of chimeric antigen receptor design." Cancer Discov 3(4): 388-398.
2. Riches, J. C., et al. (2013). "T cells from CLL patients exhibit features of T-cell exhaustion but retain capacity for cytokine production." Blood 121(9): 1612-1621
3. Saha, T., et al. (2022). "Intercellular nanotubes mediate mitochondrial trafficking between cancer and immune cells." Nat Nanotechnol 17(1): 98-106.
4. Borcherding, N. and J. R. Brestoff (2023). "The power and potential of mitochondria transfer." Nature 623(7986): 283-291.
5. Baldwin, J. G., et al. (2024). "Intercellular nanotube-mediated mitochondrial transfer enhances T cell metabolic fitness and antitumor efficacy." Cell 187(23): 6614-6630 e6621

Školitel

Mgr. Michal Šmída, Dr. rer. nat.