Vědy o živé přírodě

Annotation: 

This Ph.D. project is part of a national initiative to build a cutting-edge platform for storing and analyzing omics data, spanning genomic, epigenomic, transcriptomic, and proteomic datasets. The platform will be integrated with European networks created through the Genomic Data Infrastructure (GDI) project, enabling the sharing and analysis of data across borders, granting access to vast amounts of multi-omics data. This level of collaboration requires a federated approach, where data remains at local nodes, while computation and model training happen across distributed systems, ensuring both data privacy and security.

The primary goal of this Ph.D. will be to develop and orchestrate bioinformatics tools that leverage federated learning. These tools will facilitate scalable, collaborative computation across multiple European institutions, allowing local nodes to train models independently and contribute to a global model without centralized data storage. The Ph.D. candidate will design and deploy these federated bioinformatics tools, focusing on integrating long-read sequencing technologies - emphasizing the detection of structural variants and modeling methylation patterns - along with short-read sequencing data for a comprehensive analysis.

Federated learning will be crucial for efficiently processing the distributed datasets, allowing the platform to securely compute over sensitive data while preserving its informative value. By developing novel algorithms and workflows that integrate federated computing with omics data, the Ph.D. candidate will push the boundaries of current bioinformatics approaches. The research will lead to first-author publications, making significant contributions to both national and European scientific advancements in genomics, epigenomics, and multi-omics data integration.

Requirements for candidate:
The ideal candidate should possess strong IT skills, particularly in coding, machine learning, and data science, with a solid understanding of bioinformatics. Experience with sequencing data analysis, especially long-read and short-read technologies, is highly advantageous. Familiarity with federated computing concepts is also 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:

1.Zhao, Y., et al. “Federated Learning with Non-IID Data.” Proceedings of the 22nd International Conference on Artificial Intelligence and Statistics (2018).

2. Li, T., et al. “Federated Optimization in Heterogeneous Networks.” arXiv preprint arXiv:1812.06127 (2018).

3.Celi, L. A., et al. “Federated Learning Applications in Medicine: A Systematic Review.” PLOS Digital Health (2022).

4.Rieke, N., et al. “The Future of Digital Health with Federated Learning.” Nature Medicine 26 (2020): 1691–1700.

5.Wang, S., et al. “Privacy-Preserving Federated Learning for Bioinformatics Data Integration.” IEEE Transactions on Big Data (2022).

Školitel

Mgr. Vojtěch Bystrý, 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 literature, three salient features underlying its function in signaling 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 Ck1epsilon/sigma 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, MS-HDX) 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 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 behaviors associated with intrinsic disorder and their connection to DVL liquid-liquid phase separation?

Requirements on candidates:

Biomolecular NMR, Biochemistry, Molecular Cell Biology

More information: RG Protein-DNA Interactions

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:

Kravec M. et al. A new mechanism of posttranslational polyglutamylation regulates phase separation and signaling of the Wnt pathway protein Dishevelled. Embo J., 2024 (accepted)

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.

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.

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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: 
 
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: 
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.