Life Sciences

PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website , all interested candidates are required to contact Gabriel Demo (gabriel.demo@ceitec.muni.cz) for informal discussion.
Annotation: 
Bunyaviruses are medically important negative-strand RNA viruses whose replication and transcription are mediated by the multifunctional RNA-dependent RNA polymerase (L protein) and viral nucleoproteins (NPs). Recent cryo-electron microscopy studies have revealed the molecular architecture and conformational dynamics of bunyaviral L proteins during RNA synthesis, yet the mechanisms coordinating viral transcription with host translation remain poorly understood. Emerging evidence suggests that viral replication-transcription complexes may localize in proximity to host ribosomes and translation factors, potentially facilitating efficient viral gene expression.
The primary aim of this project is to determine how bunyavirus L proteins, nucleoproteins, and ribonucleoprotein complexes interact with host translational machinery during infection. Initial studies will employ sucrose-gradient polysome profiling, immunoblotting, and mass spectrometry to identify associations between viral replication-transcription factors and host ribosomes or translation factors. Purified viral and host components will be used in biochemical binding assays to validate direct interactions and define minimal interaction networks.
To investigate these interactions under physiologically relevant conditions, a minimal bunyavirus replication-transcription system will be established in mammalian cell lines using viral minigenome approaches. Structural characterization of identified complexes will be pursued using single-particle cryo-electron microscopy and cryo-electron tomography, enabling visualization of viral ribonucleoproteins and associated host translation components. These studies will provide mechanistic insight into how bunyaviruses coordinate RNA synthesis and translation, potentially uncovering novel targets for antiviral intervention.
Recommended literature:

1. Wang X. et al. Structure of Rift Valley Fever Virus RNA-Dependent RNA Polymerase. Journal of Virology (2022).
2. Arragain B. et al. Pre-initiation and elongation structures of full-length La Crosse virus polymerase reveal functionally important conformational changes. Nature Communications (2020).
3. Arragain B. et al. Structural snapshots of La Crosse virus polymerase reveal novel insights into replication and transcription mechanisms. Nature Communications (2022).

 Requirements for candidate:
We are seeking a highly motivated PhD candidate with an MSc degree in structural biology, biochemistry, virology, or a related field.
 
Preferred qualifications:

• Experience in molecular biology, biochemistry, or virology.
• Practical laboratory experience with protein purification, human cell cultures, or RNA biology.
• Basic knowledge of structural biology techniques, particularly cryo-electron microscopy.
• Interest in host-pathogen interactions and viral gene expression.
• Ability to work independently and collaboratively in an interdisciplinary environment.
• Good written and spoken English.

 
PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact Gabriel Demo (gabriel.demo@ceitec.muni.cz) for informal discussion.

Supervisor

Mgr. Gabriel Demo, 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.

Notes

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.

Supervisor

prof. Mgr. Richard Štefl, Ph.D.

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

Supervisor

doc. Mgr. Pavel Plevka, Ph.D.

PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website
Annotation: 
Cyclin-dependent kinase 11 (CDK11) is ubiquitously expressed in all tissues indicating an important role for CDK11 in cells. Our recent studies has shown CDK11 plays key roles in transcription of replication-dependent histone genes and in co-transcriptional mRNA splicing (1, 2). 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 is also of significant clinical interest. In this research we will use CDK11 inhibitors and advanced techniques of molecular biology and biochemistry to characterize roles of CDK11 in regulation of gene expression and tumorigenesis.
Requirements for candidate:
Background in molecular biology, biochemistry or life sciences. Interest in bioinformatics and data analyses is desirable.
Recommended literature:
1) Hluchy M, Gajduskova, P., Ruiz de los Mozos I., Rajecky M., Kluge M., Berger BT., Slaba Z. Potesil D., Weis E., Ule J., Zdrahal Z., Knapp S., Paruch K., Friedel CC., Blazek D*. CDK11 regulates pre-mRNA splicing by phosphorylation of SF3B1. Nature; 609(7928):829-834 (2022)
2) 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).

Supervisor

Mgr. Dalibor Blažek, Ph.D.

PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website
Annotation:  The development and progression of B-cell malignancies are critically influenced by signals originating from the tumor microenvironment. Over the past decade, non-coding RNAs have emerged as key regulators of cellular communication and signaling pathways in cancer. While microRNAs have been extensively studied and are known to play important roles in B-cell biology, the functions of long non-coding RNAs (lncRNAs) remain largely unexplored. Understanding how lncRNAs regulate malignant B-cell behavior represents one of the major unanswered questions in contemporary cancer biology.
This PhD project aims to uncover the role of lncRNAs in controlling B-cell receptor (BCR) signaling and B–T cell interactions, two fundamental processes that drive the pathogenesis of chronic lymphocytic leukemia (CLL). The project builds on the long-standing expertise of the research group in non-coding RNA biology and tumor–microenvironment interactions, supported by an ERC Starting Grant and multiple high-impact publications in the field. Preliminary data have identified several previously uncharacterized lncRNAs that are likely involved in regulating communication between CLL cells and their microenvironment.
The PhD candidate will investigate the molecular functions of these lncRNAs using a combination of state-of-the-art genetic, cellular, and biochemical approaches. A unique aspect of the project is the availability of newly generated lncRNA knockout mouse models, including mice carrying the genetic deletion of a candidate lncRNA. The student will characterize these models and combine them with established CLL mouse systems, including the Eu-TCL1 model, to determine the role of lncRNAs in leukemia development and progression in vivo. The project will further employ CRISPR interference technologies, RNA pulldown assays, transcriptomic analyses, and studies of primary patient-derived samples to identify molecular pathways and interaction partners controlled by candidate lncRNAs. In parallel, the student will take advantage of a recently developed co-culture system that enables robust proliferation of primary CLL cells in vitro, overcoming a major limitation in CLL research. This innovative platform will be used to perform the first CRISPR-based functional screens aimed at identifying lncRNAs and protein-coding genes that regulate the proliferation and survival of primary CLL cells. By integrating functional genomics, mouse modeling, and patient-based research, this project seeks to establish a comprehensive understanding of how lncRNAs shape B-cell signaling and microenvironmental responses in CLL. The findings are expected to reveal fundamental mechanisms of leukemia biology, identify novel therapeutic vulnerabilities, and generate insights that are broadly relevant to other B-cell malignancies, autoimmune diseases, and normal immune regulation.
This interdisciplinary project offers extensive training in molecular biology, cancer genomics, genome engineering, mouse models, and translational research, providing an excellent foundation for a scientific career in cancer and immunology research.
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.

Supervisor

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.
 

Supervisor

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.

Supervisor

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).

Supervisor

Mgr. Dalibor Blažek, Ph.D.

PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website
Annotation: 
Paramyxoviruses are membrane-enveloped RNA viruses that include major human pathogens such as measles and mumps viruses, as well as highly lethal emerging zoonotic viruses such as Nipah virus, which causes encephalitis with case fatality rates exceeding 50%. Despite their medical importance, there are currently no specific antiviral therapies targeting paramyxovirus infection.
A promising antiviral target is the process of virus assembly and budding, which is orchestrated by the viral matrix protein. Matrix acts as a molecular scaffold at the host-cell plasma membrane, coordinating the recruitment of viral components and driving membrane remodelling to enable virus release. However, current models do not fully explain how matrix specifically recognises the plasma membrane, selectively engages other viral components, and coordinates the timing of budding from the host cell.
This PhD project will investigate the structure and assembly mechanisms of selected paramyxoviruses both in situ and in vitro, using state-of-the-art cryo-electron microscopy approaches. Single-particle cryo-EM analysis will be used to determine the architecture of purified virions and to define the spatial relationships between individual viral components. Focused ion beam milling, cryo-electron tomography and subtomogram averaging will then be applied to visualise viral assembly and budding directly within virus-producing cells.
These in situ studies will be complemented by in vitro reconstitution of viral components on synthetic lipid membranes. These minimal systems will enable high-resolution cryo-EM analysis of matrix-membrane assemblies and dynamic fluorescence-based studies of assembly behaviour. Together, the project will provide new mechanistic insight into how paramyxoviruses assemble and bud from host cells.
Requirements for candidate:
Applicants should have a strong background in one or more of the following areas or related fields: structural biology, molecular biology, biochemistry, virology or biophysics. Experience with Linux-based systems and scripting would be advantageous, but is not essential.
We are equally interested in candidates who are enthusiastic about science, motivated by the project topic, keen to learn new experimental and computational methods, and driven to tackle important and challenging scientific questions. Hard skills are valuable, but curiosity, commitment and scientific ambition will be valued just as highly.

Recommended literature:
Watkinson RE, Lee B. Nipah virus matrix protein: expert hacker of cellular machines. FEBS Lett. 2016;590(15):2494-2511. doi:10.1002/1873-3468.12272

Norris MJ, Husby ML, Kiosses WB, et al. Measles and Nipah virus assembly: Specific lipid binding drives matrix polymerization. Sci Adv. 2022;8(29):eabn1440. doi:10.1126/sciadv.abn1440

Clemente CM, Mobarec JC, Bharat TAM. Applications and prospects of cryo-electron tomography in drug discovery and understanding disease. Curr Opin Struct Biol. 2026;98:103283. doi:10.1016/j.sbi.2026.103283

Supervisor

Mgr. Dominik Hrebík, Ph.D.

PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website
Annotation:  B-cell malignancies, including chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL), remain incurable diseases despite major advances in targeted therapies. Increasing evidence indicates that malignant B cells acquire profound alterations in chromatin organization, leading to aberrant activation of enhancers and promoters that drive oncogenic gene-expression programs. These changes create a permissive landscape for transcription factors (TFs), key regulators of cell fate, proliferation, and differentiation, to promote tumor growth and survival. Recent studies suggest that TF activity is further shaped by signals from the tumor microenvironment, including post-translational modifications induced by dysregulated signaling pathways. However, the identity of the critical TFs involved and the mechanisms through which they contribute to disease progression, therapeutic resistance, and interactions with the immune microenvironment remain poorly understood. This PhD project aims to uncover the role of novel transcription factors and chromatin-associated regulators in the pathogenesis of CLL, FL, and related B-cell malignancies. Building on our preliminary data, the PhD candidate will investigate TF-driven regulatory networks controlling malignant B-cell survival, proliferation, and communication with surrounding immune cells. Particular emphasis will be placed on transcriptional programs linked to the oncogene MYC and on identifying opportunities for their therapeutic disruption.
The project combines cutting-edge molecular and functional approaches, including CRISPR-based genome engineering, transcriptomic and epigenomic profiling (RNA-seq, ChIP-seq), analysis of primary patient samples, testing of inhibitors, and studies in advanced in vitro and in vivo mouse models, including in vivo CRISPR screening. The candidate will also evaluate emerging therapeutic strategies targeting transcription factors and chromatin regulators, with the goal of identifying new vulnerabilities that can be exploited for treatment. This interdisciplinary project offers training at the interface of cancer biology, genomics, epigenetics, and translational research, providing an opportunity to contribute to the development of next-generation therapies for B-cell malignancies.
 Requirements for candidate:

• 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.

Recommended literature:
Beekman et al. The reference epigenome and regulatory landscape of chronic lymphocytic leukemia. Nature Medicine 2018
https://pubmed.ncbi.nlm.nih.gov/29785028/
 
Sun et al. The immune microenvironment shapes transcriptional and genetic heterogeneity in chronic lymphocytic leukemia. Blood Advances 2022
https://pubmed.ncbi.nlm.nih.gov/35358998/
 
 

•  

Supervisor

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

Supervisor

doc. Mgr. Pavel Plevka, Ph.D.

PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website
Annotation: 
The bottom-up construction of an autonomously dividing minimal cell would represent a major advance in synthetic cell biology and provide a stringent test of our understanding of the fundamental principles of life, particularly the mechanisms that drive cell division. Decades of research have established Bacillus subtilis as a model organism for studying cell division in Gram-positive bacteria. However, despite substantial progress, a high-resolution structure of the bacterial division machinery remains elusive.
This PhD project will investigate the structure and assembly mechanism of the bacterial division Z-ring both in situ and in vitro, using a combination of focused ion beam milling, cryo-electron tomography, subtomogram averaging and single-particle cryo-EM analysis. The student will first optimise strategies to arrest cell division at a defined stage, enabling Z-ring structures to be averaged across multiple cells. They will then develop an approach for orienting cells perpendicular to the cryo-EM grid, facilitating downstream FIB-milling and high-resolution cryo-electron tomography.These methods will be used to determine the architecture of the Z-ring in its native cellular context.
In parallel, the student will support the in situ observations with in vitro reconstitutions of the division complex on artificial membranes, followed by structural analysis using cryo-EM. Together, these approaches will provide new insight into the molecular organisation and assembly of the bacterial cell division machinery, with broader implications for the design of antibiotics targeting cell division, synthetic cell biology and the design of minimal dividing cells.
Requirements for candidate:
Applicants should have a strong background in one or more of the following areas or related fields: structural biology, molecular biology, biochemistry or biophysics. Experience with Linux-based systems and scripting would be advantageous, but is not essential.
We are equally interested in candidates who are enthusiastic about science, motivated by the project topic, keen to learn new experimental and computational methods, and driven to tackle important and challenging scientific questions. Hard skills are valuable, but curiosity, commitment and scientific ambition will be valued just as highly.
Recommended literature:
Cameron TA, Margolin W. Insights into the assembly and regulation of the bacterial divisome. Nat Rev Microbiol. 2024;22(1):33-45. doi:10.1038/s41579-023-00942-x

Clemente CM, Mobarec JC, Bharat TAM. Applications and prospects of cryo-electron tomography in drug discovery and understanding disease. Curr Opin Struct Biol. 2026;98:103283. doi:10.1016/j.sbi.2026.103283

Errington J, Wu LJ. Cell Cycle Machinery in Bacillus subtilis. Subcell Biochem. 2017;84:67-101. doi: 10.1007/978-3-319-53047-5_3. PMID: 28500523; PMCID: PMC6126333.

Klumpe S, Plitzko JM. Cryo-focused ion beam milling for cryo-electron tomography: Shaping the future of in situ structural biology. Curr Opin Struct Biol. 2025;94:103138. doi:10.1016/j.sbi.2025.103138

Supervisor

Mgr. Dominik Hrebík, 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.

Supervisor

doc. Mgr. Pavel Plevka, Ph.D.

PLEASE NOTE: Before starting the formal application process, applicants must register on the CEITEC PhD School website

Annotation: 
Every organism faces a constant battle against invading genetic elements such as viruses and plasmids. To survive, bacteria and archaea have evolved a remarkable diversity of immune systems that detect and eliminate foreign DNA. Traditionally, these systems have been studied as independent defense mechanisms. However, recent discoveries suggest that some immune systems cooperate, forming more complex defense networks capable of responding to a broader range of threats.

One particularly intriguing example is provided by prokaryotic Argonaute proteins (pAgos), programmable nucleic-acid recognition factors found throughout bacteria and archaea. While some pAgos directly destroy invading DNA, many are genetically associated with proteins belonging to entirely different immune pathways. Why these systems became linked during evolution and how they cooperate at the molecular level remains unknown.
This PhD project will investigate how Argonaute proteins interact with partner immune systems to create novel defense strategies. Using state-of-the-art electron cryomicroscopy (cryo-EM), the student will determine structures of immune complexes captured at different stages of substrate recognition, remodeling, and processing. These structural studies will be complemented by biochemical, biophysical, microbiological, and evolutionary analyses performed in collaboration with leading international laboratories.
A particular focus will be understanding how catalytically inactive Argonautes have evolved into programmable regulators of partner immune proteins and how such cooperation increases the complexity and robustness of microbial immunity. By visualizing molecular machines in action and uncovering their dynamic mechanisms, the student will reveal fundamental principles governing the evolution and organization of immune systems.
The project sits at the interface of structural biology, microbiology, evolutionary biology, and biophysics, providing training in cryo-EM, protein biochemistry, computational structural biology, and molecular mechanism discovery.
Join us to uncover how evolution creates new immune systems by combining existing ones into more powerful defense machines.

Requirements for candidate:
Biochemistry/molecular biology/strucktural biology
Recommended literature:
1) Koopal B. et al. Diverse prokaryotic Argonaute-associated immune systems. Science (2023).
2) Ugarte R. et al. Molecular mechanisms of Argonaute-associated defense systems. Mol Cell (2025).
3) Makarova KS et al. Evolutionary classification of CRISPR-Cas systems. Nat Rev Microbiol (2020).
4) Swarts DC et al. Prokaryotic Argonautes: mechanisms and biological roles. Nat Rev Microbiol.
5) Finocchio G. et al. Cooperation between prokaryotic immune systems.
 

Supervisor

prof. Mgr. Richard Štefl, Ph.D.