Molecular and Cell Biology and Genetics

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

Submit an application

International applicants for doctoral study (Czech and Slovak Republics applicants not included)
Submission deadline until midnight 15 December 2022.

What will you learn?

The program is a product of the fusion of former independent Molecular and Cellular Biology with General and Molecular Genetics. We propose the fusion to reflect modern holistic approaches dominating in both fields that converge them to close proximity and bring benefits to both of them. The aim of the program is to provide excellent scientific education in the field of molecular and cell biology and genetics. The graduates thus should be proficient to accomplish research of the nature of living phenomena on molecular, cellular, tissue and organismal levels. To achieve this aim, students are systematically guided to advance their theoretical knowledge in the field and master practical skills in applications of modern methods of molecular and cellular biology, genetics and other related fields. The key themes include the study of genes and genomes and their expression in microorganisms, plants, animals and humans. Special attention is paid to their relations to pathological conditions. Research performed on microorganisms is focused preferentially on molecular diagnosis and genomics of selected pathogenic and clinically significant bacterial strains and their interactions with bacteriophages. Research on plants is concentrated mainly on the study of genes of model plants and plants used in agriculture. In animals and humans, research is focused on the genetical structure of populations, molecular diagnosis of prenatal and postnatal pathogenic situations, genetics of tumours, the study of signalling processes connected with the regulation of proliferation, differentiation and programmed cell death in tumour cells and detection of genetical factors associated with certain polygenic diseases. Students are free to perform independent research in well-equipped laboratories and experienced supervisors are nominated to guide them in this effort. Students are continuously confronted with progress in the field by discussions in regular laboratory meetings, institutional seminars or conferences. Successful conference presentations or published articles are awarded by a special stipend.

“Windows of the living cell universe wide-opened.”

Practical training

The students who are interested in applied research can collaborate with companies as Repromeda (assisted reproduction), MB Pharma (devising phage preparations) or to participate in grant projects funded by TACR leading to applied outcomes. We aim to further support contractual research with applied potential, search for suitable partners and provide them with option to collaborate with students interested in this kind of research.

Further information

Additional information can be found in following addresses:

http://www.sci.muni.cz/cz/DoktorskeStudium/Prehled-programu-a-oboru

http://www.sci.muni.cz/cz/UEB

Career opportunities

Graduates find positions in various research institutes, universities, hospitals and other medical facilities and laboratories oriented to virology, microbiology, genetics, biochemistry, immunology, pharmacology, pathology, etc. They are ready to perform independent research, draft scientific projects, create grant applications, experimental work itself, including rigorous interpretations of results and presentations in oral as well as written forms. They are also educated to act as teachers. Graduates from this program are sought-after by employers and many of them currently work on positions of leading researchers, university teachers, top managers and directors in various research and education institutions in the Czech Republic. Many graduates leaves for postdoctoral stays abroad, especially to westeuropean countries, USA, Canada, Japan, Australia. They often become highly-appreciated members of research teams there.

Admission requirements

Admission procedure
The admission interview is usually in an online form and consists of two parts:
1) expert interview – checking expertise background and motivation (max. 100 points),
2) Language part – check of communication skills in English, interview and expert discussion is in English (max. 100 points)

More information about admission process for international applicants in general can be found here.

Date of the entrance exam
The applicants will receive information about the entrance exam by e-mail usually at least 10 days before the exam.
Please, always check your e-mails, including spam folders.

Conditions of admission
To be admitted, a candidate must obtain a total of 70 out of 100 points in the expert knowledge part and 60 out of 100 points in the language part.
Successful applicants are informed of their acceptance by e-mail and subsequently receive an invitation to the enrolment.

Programme capacity
The capacity of a given programme is not fixed; students are admitted based on a decision by the Doctoral Board after assessing their aptitude for study and motivation.

Deadlines

2 May – 15 Dec 2022

Submit your application during this period

Submit an application

Dissertation topics

Single-subject studies

Function of Cdk13 in the cellular signaling
Supervisor: Mgr. Jiří Kohoutek, Ph.D.

Rodina cyklin-dependentních kináz (CDK) se podílí na řízení celé řady buněčných pochodů a fyziologických procesů v rámci celého organismu. Historicky byly CDK poprvé popsány v souvislosti s jejich úlohou v regulaci buněčného cyklu. Kromě funkce v buněčném cyklu CDK hrají nezastupitelnou úlohu v translaci, replikaci, apoptóze a transkripci. A právě CDK13 je kináza, jejíž kinázová aktivita je nezbytná pro správný průběh transkripce. CDK13 fosforyluje RNA polymerázu II a tím řídí průběh jednotlivými fázemi transkripce. Ztráta funkce CDK13 je pro organismus kritická a vede k embryonální letalitě v důsledku nesprávného vývoje celé řady orgánů a orgánových struktur. Nicméně mechanismy, které jsou negativně ovlivněny ztrátou CDK13 aktivity jsou zatím neznámé. Cílem disertační práce bude určení role CDK13 v buněčné signalizaci a přestavbě cytoskeletu. K tomuto záměru budou využity coby modelové systémy transgenní kmeny myší, primární buněčné linie izolované z daných vývojových stádií orgánů a další modelové buněčné linie. Ke studiu funkce CDK13 budou použity pokročilé molekulárně biochemické metody a mikroskopické metody.

Supervisor

Mgr. Jiří Kohoutek, Ph.D.

In vivo characterization of dentition related stem cells - cellular and molecular aspects
Supervisor: prof. RNDr. Eva Matalová, Ph.D.

Kmenové buňky jsou zdrojem pro obnovu tkání v rámci homeostáze, ale také výzvou pro regenerativní medicínu. Jednou z komplikací při aplikaci zubních implantátů je jejich funkční ukotvení v čelisti, které u nativních zubů zajišťuje závěsný aparát. Kmenové buňky získané z periodontálních ligament závěsného aparátu zubu byly dosud charakterizovány zejména in vitro. Cílem vědecko-výzkumné práce bude získat co nejvíce dat k jejich in vivo lokalizaci a potenciálu z hlediska vývoje i údržby struktur, pozornost bude zaměřena také na jejich uplatnění při zánětových procesech (parodontóza).
Projekt zahrnuje metody in situ detekce proteinů, transkripční analýzy, časoprostorové korelace, experimentální modulace, statistická hodnocení dat atp. Základním modelem je myš, s extrapolacemi do humánní sféry. U kandidáta je důležitá motivace, zájem o osvojení nových metod, precizní provádění a hodnocení experimentů, přínos k poznání v daném oboru a schopnost komunikace v angličtině. Téma je vypsáno k aktuálně řešenému projektu GAČR (ve spolupráci s Kings College London).

Supervisor

prof. RNDr. Eva Matalová, Ph.D.

Inflammatory factors displayed on tumor cell surface: juxtracrine signaling to stromal compartment
Supervisor: doc. Mgr. Petr Beneš, Ph.D.

Chronic inflammation and proinflammatory cytokines such as interleukin 1 are considered to be tumour promoting. However, membrane anchorage of IL-1 alpha was found to provoke immune stimulatory signaling. Macrophages use membrane-associated form of IL-1alpha as a co-stimulatory molecule for T-lymphocytes activation. Fibrosarcoma cells with constitutive expression of membrane-bound IL-1 alpha elicited a strong anti-tumor immune response. The biologically active membrane-associated form of IL-1 alpha is anchored to the cell membrane via a mannose-like receptor and accumulates in response to oxidative stress, however, the mechanism and regulators of its membrane integration, as well as dynamics of its subcellular distribution during tumor dissemination are not known. A growing body of evidence indicates that metastasis initiation may be the culmination of a highly fluid process involving cell surface camouflage, dynamic interactions between clonal tumor populations and stromal components. Non-canonical externalization pathway of IL-1 alpha and its membrane-associated juxtacrine signaling is therefore of interest not only in context of cancer immunotherapy.

Supervisor

doc. Mgr. Petr Beneš, Ph.D.

Molecular factors associated with vascularization, innervation and stem cells of the dental pulp
Supervisor: Mgr. Eva Švandová, Ph.D.

Zubní pulpa představuje cévní a nervové zásobení zubu obklopené jeho tvrdými komponentami. Jedná se o unikátní tkáň, která je klíčová pro vitalitu zubu, současně náchylná na působení zevních vlivů a vykazující omezenou míru regenerace. Kmenové buňky, které byly identifikovány v zubní pulpě, jsou proto atraktivním předmětem biomedicínského výzkumu. Obecně je známo, že výskyt kmenových buněk je asociován s vaskularizací a inervací tkání, většina poznatků ke kmenovým buňkám zubní pulpy však pochází z in vitro analýz. Cílem vědecko-výzkumné činnosti bude výzkum molekulárních faktorů týkajících se těchto asociací, a to v kontextu in vivo. Projekt zahrnuje zejména histologické a imunohistochemické metody, PCR techniky, statistickou analýzu dat a experimentální práci na myším modelu. K pozici je možné získat částečný úvazek na běžícím GAČR projektu. Kandidát na tuto pozici by měl samostatně pracovat s odbornou literaturou a být všeobecně orientován v oboru molekulární biologie. Znalost výše uvedených technik není nutná.

Notes

This project will be supervised by dr. Eva Švandová, Ph.D upon approval by Scientific Board of the Faculty of Science.

Supervisor

Mgr. Eva Švandová, Ph.D.

Molecular mechanisms controlling chromosome segregation in oocytes and early embryos
Supervisor: doc. MVDr. Martin Anger, CSc.

Cílem projektu je popis molekulárních mechanismů regulujících segregaci chromozomů v oocytech a časných embryích savců za pomocí časosběrné a vysokorozlišovací mikroskopie a také dalších přístupů pokročilé mikroskopie, také za použití přístupů a technik molekulární a buněčné biologie. Během studia budou použity metody vícekanálové fluorescenční mikroskopie pro sledování paralelních událostí v rámci buněčného cyklu a budou objasněny souvislosti mezi poruchami segregace chromozomů a kontrolními procesy, odehrávajícími se na molekulární úrovni.

Supervisor

doc. MVDr. Martin Anger, CSc.

Molecular pathogenesis of giant cell tumor of bone
Supervisor: doc. RNDr. Jakub Neradil, Ph.D.

Giant-cell tumor of bone (GCTB) is an intermediate type of primary bone neoplasia, characterized by local aggressive growth and low metastatic potential. This neoplasm is associated with a wide range of biological behaviors ranging from latent benign to locally aggressive growth with destruction of the cortex and soft tissue extension. Histologically, GCTB contains 2 groups of cells, osteoclast-like giant cells and mononuclear neoplastic (stromal) cells. The main aim of this thesis is to describe molecular characteristics of both cell populations and their signaling interactions. These new results could bring new insights in the search for new therapeutic targets in treating GCTB.

Notes

More information: http://www.sci.muni.cz/ltb/phd-2020/.

Supervisor

doc. RNDr. Jakub Neradil, Ph.D.

Novel molecular interactions related to signalling pathways mediated by receptors from TNF and TGF families in osteogenesis
Supervisor: prof. RNDr. Eva Matalová, Ph.D.

Vývoj a homeostáze kostí podléhá molekulárnímu řízení, které zahrnuje členy rodin TNF a TGF. Výzkum bude zaměřen na nové interakce týkající se zejména receptoru CD95 a jeho ligandu CD178, z rodiny TGF pak především TGFbeta3. V centru zájmu budou osteocyty jako klíčová populace buněk maturovaných kostí, která se podílejí na signalizaci i metabolismu, dále pak osteoblasty a osteoklasty. Cíle navazují na dosavadní poznatky získané na školicím pracovišti, které na daném tématu spolupracuje s University of Southern California a Medizinische Universitaet Wien. Projekt zahrnuje práci se vzorky geneticky modifikovaných organismů, základem je myší model a analýzy na úrovni transkriptomu a proteomu, a to in vitro i v kontextu tkání. Výzkum je zastřešen projekty Inter-Excellence.

Supervisor

prof. RNDr. Eva Matalová, Ph.D.

Organotypic cultures for testing of targeted drug efficacy
Supervisor: Mgr. Jarmila Navrátilová, Ph.D.

Currently, more than half of all drugs fail in late-stage clinical trials due to a lack of efficacy, even though exhibiting high cytotoxicity in preclinical settings. This failure might result from the inappropriate models for pre-clinical drug testing, such as cell monolayers. Therefore, the dissertation will focus on 3D systems for drug testing: the spheroids and the organotypic slice cultures (OTSC). Both of these models provide more accurate conditions reflecting the tissue environment in vivo, such as hypoxia, acidosis, concentration gradients for nutrients, and others. The student will standardize the protocol for OTSC generation and cultivation; OTSC morphology and protein expression will be compared with the primary tumor. Then, the student will define signaling pathways deregulated in OTSC and select combined therapy effectively eliminating cancer cells and preserving the viability of healthy tissue. Moreover, the interaction between specific bacterial species enriched in cancer patients, OTSC, and the effect of therapy will be determined.

Notes

Po schválení Vědeckou radou PřF MU bude školitelkou práce dr. Jarmila Navrátilová.

Supervisor

Mgr. Jarmila Navrátilová, Ph.D.

Post-polyploid genome evolution in the mustard family (Brassicaceae)
Supervisor: RNDr. Terezie Malík Mandáková, Ph.D.

Notes

Školitelkou práce bude po schválení Vědeckou radou PřF MU Dr. Terezie Mandáková, Ph.D.

Supervisor

RNDr. Terezie Malík Mandáková, Ph.D.

Proteins interactions with DNA, focus on local DNA structures
Supervisor: prof. Mgr. Václav Brázda, Ph.D.

Genome sequencing brings a huge amount of information regarding the genetic basis of life. While this information provides a foundation for our understanding of biology, it has become clear that the DNA code alone does not hold all the answers. Epigenetic modifications and higher order DNA structures beyond the double helix contribute to basic biological processes and maintaining cellular stability. Local alternative DNA structures are known to exist in all organisms. Negative supercoiling induces in vitro local nucleotide sequence-dependent DNA structures such as cruciforms, left-handed DNA, triplex and quadruplex structures etc. The formation of cruciforms requires perfect or imperfect inverted repeats of 6 or more nucleotides in the DNA sequence. Inverted repeats are distributed nonrandomly in the vicinity of breakpoint junctions, promoter regions, and at sites of replication initiation. Cruciform structures could for example affect the degree of DNA supercoiling, the positioning of nucleosomes in vivo, and the formation of other secondary structures of DNA. The three-dimensional molecular structure of DNA, specifically the shape of the backbone and grooves of genomic DNA, can be dramatically affected by nucleotide changes, which can cause differences in protein-binding affinity and phenotype. The recognition of cruciform DNA seems to be critical not only for the stability of the genome, but also for numerous, basic biological processes. As such, it is not surprising that many proteins have been shown to exhibit cruciform structure-specific binding properties or G-quadruplex binding properties. Contemporary we have developed easy accessible web tools for analyses of inverted repeats and G-quadruplexes and we have analyzed the presence of inverted repeats and G-quadruplexes in various genomic datasets, such as all sequences mitochondrial genomes, all bacterial genomes, in S.cerevisiae, in human genome etc. A deeper understanding of the processes related to the formation and function of alternative DNA structures will be an important component to consider in the post-genomic era.

Notes

Supervisor:
Doc. Mgr. Václav Brázda, PhD.; Biofyzikální ústav AVČR, Královopolská 135, 612 65 Brno, tel. 541517231, fax 541211293, e-mail: vaclav@ibp.cz
https://www.ibp.cz/en/research/departments/biophysical-chemistry-and-molecular-oncology/staff/5

Supervisor

prof. Mgr. Václav Brázda, Ph.D.

Quantitative analysis of the cell cycle using live cell imaging and advanced microscopy
Supervisor: doc. MVDr. Martin Anger, CSc.

Cílem projektu je analýza buněčného cyklu za pomocí metod časosběrné a funkční mikroskopie. Studována bude dynamika změn hladiny a lokalizace proteinů řídících průběh buněčného cyklu a také aktivita enzymů v živých buňkách. Použité techniky budou zahrnovat taktéž mikromanipulace buněk, transfer jader a pokročilé postupy vícekanálové konfokální mikroskopie. K analýze dat bude využíván komerční i volně dostupný software pro analýzu obrazu. Smyslem práce je popsat kvantitativní změny na úrovni proteinů u buněk v průběhu buněčného cyklu a zjistit jakým způsobem dochází v procesu dělení buněk k nejčastějším chybám.

Supervisor

doc. MVDr. Martin Anger, CSc.

Regulation of DNA replication origins during cancer development
Supervisor: Mgr. Hana Polášek-Sedláčková, PhD.

DNA replication is essential process to copy genetic information in proliferating cells. Understanding how the cell regulates DNA replication remains one of the most fundamental questions in biomedicine, because up to two-thirds of all cancers are caused by the accumulation of errors during DNA replication. Pre-replicative complexes (pre-RCs) serve as essential precursors for DNA replication and their accurate levels are critical to alleviate genome instability associated with severe diseases, including cancer. Indeed, the overexpression of pre-RCs has been reported at early stages of variety of cancers making them an attractive target for cancer therapy. However, the molecular mechanism(s) of precise pre-RC formation and their roles in safeguarding genome integrity is incompletely understood.
The aim of this project is to decipher regulatory foundations of DNA replication and uncover the mechanisms controlling the assembly of pre-RCs and their roles in protecting genome integrity. By combining physiologically relevant mammalian cellular models with state-of-the-art CRISPR-Cas9 genome editing, quantitative cell biology, genomics, and proteomics approaches we will investigate signaling pathways responsible for optimal levels of pre-RCs and their contribution to genome instability during oncogene-induced tumorigenesis. Besides underpinning the basic regulatory foundations of human genome protection, our findings may inspire the development of new anticancer drug targets and thereby expand therapeutic strategies for treatment of cancer associated with mis-regulated pre-RC levels and poor prognosis.

Notes

Školitelem bude Mgr. Hana Polášek-Sedláčková, Ph.D. z Biofyzikálního ústavu AV ČR, e-mail: polasek-sedlackova@ibp.cz

Supervisor

Mgr. Hana Polášek-Sedláčková, PhD.

RNA modifications and DNA repair
Supervisor: doc. RNDr. Eva Bártová, Ph.D., DSc.

Cells have evolved multiple conserved mechanisms for maintaining genome integrity, collectively termed the DNA-damage response (DDR). DDR process identifies and repairs different types of injury in the genome; for example, cyclobutane pyrimidine dimers (CPDs) or other oxidative DNA lesions. Very deleterious are the double-strand breaks, which erroneous repair leads to tumorigenesis or nonsense mutations. Xiang et al. (2017) showed that RNA methylation N6methyladenosine; m6A) regulates DNA damage response in cells exposed to UV radiation. Similarly, as methylated RNA appears at UV-damaged chromatin, relevant methyltransferase METTL3 is recruited to UV-damaged genomic regions, but METTL3 knockout did not affect RPA, 53BP1, and BRCA1 recruitment to micro-irradiated chromatin. A pronounced UV-induced recruitment of METTL3 to the sites with DNA lesions was found to be dependent on the DNA damage-related function of PARP1 because PARP inhibitor abrogated METTL3 recruitment to UV-damaged chromatin. Moreover, METTL3 and METTL14 function parallel with Polymerase K playing a role in several DNA repair pathways. DNA polymerase K (Pol K) co-localizes with m6A in mRNA at damaged chromatin that is abundant on cyclobutane pyrimidine dimers (CPDs). In addition to this observation, we have found that not only m6A RNA but also m8A and ac4C-modified RNAs recognize microirradiated chromatin (Kovarikova Svobodova et al., Res. Square 2021; and Legartova et al., Res. Square, 2021). Student will study how modified RNAs work at DNA lesions. He/she will solve a question if the functioning of such modified RNAs should be linked to the formation of hybrid RNA-DNA loops.

Jazyk práce: čeština, angličtina nebo slovenština (zajistíme slovenského oponenta)

Literatura:
Arango, D. et al. Acetylation of Cytidine in mRNA Promotes Translation Efficiency. Cell 2018 175, 1872-1886.e1824. 10.1016/j.cell.2018.10.030
Ito, S. et al. Human NAT10 is an ATP-dependent RNA acetyltransferase responsible for N4-acetylcytidine formation in 18 S ribosomal RNA (rRNA). J Biol Chem 2014 289, 35724-35730. 10.1074/jbc.C114.602698
Sharma, S. et al. Yeast Kre33 and human NAT10 are conserved 18S rRNA cytosine acetyltransferases that modify tRNAs assisted by the adaptor Tan1/THUMPD1. Nucleic Acids Res 2015 43, 2242-2258. 10.1093/nar/gkv075
Xiang, Y. et al. RNA m6A methylation regulates the ultraviolet-induced DNA damage response. Nature 2017 543, 573-576. 10.1038/nature21671
Svobodová Kovaříková, A. et al. N(6)-Adenosine Methylation in RNA and a Reduced m(3)G/TMG Level in Non-Coding RNAs Appear at Microirradiation-Induced DNA Lesions. Cells 2020 9. 10.3390/cells9020360
Legartova Sona, S.J., Bartova Eva (2021). PARP dependent recruitment of RNA methylated at 8-adenosine is linked to base excision repair mechanism. Research Square, DOI: https://doi.org/10.21203/rs.3.rs-892499/v1
Alena Kovaříková Svobodová, Lenka Stixová, Aleš Kovařík, Eva Bártová (2021). PARP dependent acetylation of N4-cytidine in RNA appeared in UV-damaged chromatin. Research Square DOI:10.21203/rs.3.rs-971100/v1
Supervisor

doc. RNDr. Eva Bártová, Ph.D., DSc.

Structural and Biochemical Studies of Engineered Enzymes
Supervisor: Ing. RNDr. Martin Marek, Ph.D.

Enzymes catalyse most of the chemical reactions that occur in biological systems and can be given non-natural catalytic functions by protein engineering. However, despite their vast importance, we do not know how enzymes acquire the structural diversity and conformational flexibility that enables them to evolve towards new molecular functions. Our proof-of-concept data on three structurally similar but functionally distinct enzyme classes of haloalkane dehalogenases (EC 3.8.1.5), beta-lactone decarboxylases (EC 4.1.1.114), and light-emitting monooxygenases (EC 1.13.12.5) suggest that specific molecular elements – access tunnels and flexible loops – play a pivotal role in their functional diversification. The role of these molecular elements for protein evolution and function is insufficiently explored.
The proposed project will investigate the molecular structures of these model enzymes using an innovative multi-method biology approach to identify the key structural and dynamic elements that govern enzymes’ evolvability. This project will combine X-ray crystallography, single-particle cryo-electron microscopy, and advanced mass spectrometry techniques to capture unprecedented molecular details of the conformational sampling that is required for productive enzymatic biocatalysis. Complementary protein simulations, mutational and biochemical experiments will delineate the evolutionary trajectories that lead to the emergence of novel enzymatic functions. The resulting knowledge will extend our understanding of molecular evolution beyond the current state-of-the-art, particularly by revealing how the conformational diversity of proteins is associated with specific biocatalytic functions. The gained knowledge from this project will pave the way for the development of new theoretical concepts and cutting-edge software tools for the rational engineering of tailor-made biocatalysts exploitable in biotechnology and biomedicine.

Notes

Školitelem práce bude po schválení Vědeckou radou PřF MU dr. Martin Marek.

Supervisor

Ing. RNDr. Martin Marek, Ph.D.

Study of emergence of bacterial resistance to phages in staphylococci
Supervisor: prof. RNDr. Roman Pantůček, Ph.D.

Medical world is currently facing increasing antibiotic resistance and phage therapy provides a promising alternative. One of its limitation is possibility of emergence of bacterial strains resistant to phages. However, phages evolve together with their hosts and develop strategies to overcome bacterial resistance. Dynamics of this coevolution process and its impact on using phages as antimicrobial agents in staphylococci is still unclear. The aim of this thesis is to identify mechanisms responsible for bacterial resistance, their effect on phenotype and describe how these processes change over time. Three topics will be included, each with the potential of publication in scientific journal. Firstly, studied staphylococcal phages will be characterized on molecular biological level. Secondly, phage resistant mutants of bacteria will be obtained, mechanisms involved in acquisition of resistance will be determined by genomic analysis and methods of molecular cloning and site-directed mutagenesis. Thirdly, dynamics of coevolution process and its impact on host ranges of phages will be evaluated in time-shift assay. Topics have practical application in terms of assessing the role of bacterial resistance to phages in phage therapy and finding ways how to combat it. Phd student will cooperate on grant projects of the laboratory as well as with international laboratories focused on staphylococcal research.

Supervisor

prof. RNDr. Roman Pantůček, Ph.D.

The molecular role of the prominin-1/CD133 protein in cancer cells
Supervisor: prof. RNDr. Renata Veselská, Ph.D., M.Sc.

Prominin-1 (CD133) is a pentaspan transmembrane glycoprotein widely used to identify various stem cells, including cancer stem cells. Although CD133 is preferentially localized in highly curved plasma membrane protrusions, its presence in various subcellular compartments in cancer cells have been described by our group and others. CD133 was reported to be involved in cell signaling, mainly via PI3K/Akt and Src/FAK pathways induced by phosphorylation at two prominent sites (Y828 and Y852) identified in the CD133 molecule. However, the physiological function of CD133 in relation to its distribution within a cell remains largely elusive. This thesis will aim to characterize the dynamics of subcellular distribution of CD133 and elucidate its molecular role in cancer cells. The project will utilize advanced microscopy techniques, cell and molecular biology methods, and functional assays to gain better insight into the biological function of the CD133 protein in cancer.

Supervisor

prof. RNDr. Renata Veselská, Ph.D., M.Sc.

The p53 family proteins in the regulation of stemness in pediatric sarcomas
Supervisor: RNDr. Jan Škoda, Ph.D.

Pediatric sarcomas comprise about 15% of all pediatric malignancies. Despite the improved therapeutic options, pediatric sarcomas remain a serious clinical challenge. More than 30% of children with sarcoma suffers recurrence and dissemination of disease, with subsequent survival rates of only 20%. Hence, uncovering the mechanisms underlying the induction of therapy resistance in sarcomas is crucial for developing efficient treatment strategies. Our previous results indicate that aggressive sarcoma cells exhibit enhanced expression of transcription factors that are directly involved in the maintenance of stem cell traits. Although the p53 protein is the most-studied tumor suppressor and central mediator of cellular responses to stress, the wild-type p53 activity has only recently been demonstrated as a constraint in cellular reprogramming towards stemness. As an aberrant function of the p53 family proteins is often observed in pediatric sarcomas, this thesis will aim to functionally assess the potential link between impaired p53 activity and expression of stemness factors in pediatric sarcomas. Importantly, in collaboration with our international partners (LAQV/REQUIMTE, University of Porto), the effects of pharmacological re-activation of the p53 proteins will be evaluated in vitro and in vivo to gain further knowledge about the therapeutic utility of p53-mediated targeting of stemness factors in aggressive pediatric sarcomas.
This project will be supervised by dr. Jan Skoda, Ph.D upon approval by Scientific Board of the Faculty of Science. Before initiating the formal application process to doctoral studies, interested candidates are required to contact Dr. Jan Škoda for informal discussion. More information: http://www.sci.muni.cz/ltb/phd-2020/
Notes

This project will be supervised by dr. Jan Skoda, Ph.D upon approval by Scientific Board of the Faculty of Science. Before initiating the formal application process to doctoral studies, interested candidates are required to contact Dr. Jan Škoda for informal discussion. More information: http://www.sci.muni.cz/ltb/phd-2020/

Supervisor

RNDr. Jan Škoda, Ph.D.

Use of protease sensitive ferritins for transfer of pharmaceutically active compounds to target cells
Supervisor: Mgr. Vladimír Pekařík, Dr.

Feritiny jsou multipodjednotkové proteiny, kterých se často využívá pro přenos léčiv do cílových buněk. Tyto proteiny jsou velmi stabilní, což usnadňuje jejich izolaci a manipulaci s nimi, ale extrémní stabilita muže také bránit uvolňovaní do nich uzavřeného léčiva. Proto jsme v naší laboratoři připravili několik feritinů, které mají vnesené místo pro lysozomální proteázy. Úkolem studenta bude optimalizace uzavírání léčiv a fluorescenčních sond, ověření buněčné internalizace feritinového komplexu s danými látkami a jejich uvolňování uvnitř buňky. Dalším krokem budou povrchové modifikace feritinu, které mají za cíl zvýšit afinitu komplexu k nádorovým buňkám anebo aktivovat proteolytickou degradaci proteinu.

Supervisor

Mgr. Vladimír Pekařík, Dr.

Supervisors

Study information

Provided by Faculty of Science
Type of studies Doctoral
Mode full-time Yes
combined Yes
distance No
Study options single-subject studies Yes
single-subject studies with specialization No
major/minor studies No
Standard length of studies 4 years
Language of instruction English
Collaborating institutions
  • The Czech Academy of Sciences
  • Biofyzikální ústav AV ČR
Doctoral board and doctoral committees
Tuition fees
The studies are subject to tuition, fees are paid per academic year
€3,000
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