Molecular and Cell Biology and Genetics

Windows of the living cell universe wide-opened.

What will you learn?

The program is product of 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 bringing benefits to both of them. The aim of the program is providing excellent scientific education in the field of molecular and cell biology and genetics. The graduates thus should be proficient to accomplish research of living phenomena on molecular, cellular, tissue or 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 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 of plants is concentrated mainly on genes of model plants and plants used in agriculture. In animals and humans, research is focused on genetical structure of populations, molecular diagnosis of prenatal and postnatal pathogenic situations, genetics of tumors, study of signalling processes connected with deregulation of proliferation, differentiation and programmed cell death in tumor 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. Students successfully presenting their results in conferences or written articles can be awarded by special scholarships for excellent representation of the Deparmtent of Experimental Biology and following activities:

1. Successfull presentation record resulting from reaching aims of Ph.D. thesis projects, such as:

  • papers in international journals or chapters in monographies, considering ranking of the journal (IF, Q), placings of the student among co-authors, number of co-authors, proportion of the student efforts on the published results.
  • presentation of the results on conferencies, considering placings of the student amnog co-authors, number of co-authors, proportion of the student efforts on the published results and the type of the conference (international or domestic).

The scholarship can be used for partial covering of travel/accomodation expenses or conference fees.

The essential condition for awarding the scholarship is correct affiliation of the presentations (both papers and conference abstracts) to the Deparment of Experimental Biology, Faculty of Science, Masaryk University.

2. Participation in teaching younger students of Master programmes how to perform experimental methods and interprete the results obtained.

3. Participation in grant projects. Long-lasting participation and significant contribution to accomplishing the projects aims can be awarded by getting part-time job or contract for certain period.

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, design experimental work itself, interprete results rigorously and present them 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 Brno, Prague, Ostrava, České Budějovice, Olomouc, etc. Many graduates leaves for postdoctoral stays abroad, especially to west-european countries, USA, Canada, Japan, Australia. They often become highly-appreciated members of research teams there.

Admission requirements

Data from the previous admission procedure (1 Jan – 30 Apr 2020)

Expert part: 0-100 points, minimum for admission: 70 points Language part: 0-100 points, minimum for admission: 60 points Minimum for admission: 130 points

Criteria for evaluation

No information available

Application guide

Supervisors and dissertation topics

Supervisors

Dissertation topics

Single-subject studies

Diet reconstruction by usage methods of molecular biology in historical populations with regards on composition of diet and intestinal fill

Supervisor: doc. RNDr. Eva Drozdová, Ph.D.

Výzkum se bude týkat rekonstrukce složení potravy s využitím lidského kosterního materiálu, zubního kamene a střevního obsahu. Cílem bude identifikace proteinů obsažených v potravě a střevním obsahu. Za účelem poznání jejích složek, případně složení jídel, která zkoumaní lidé konzumovali. Druhou složkou výzkumu bude studium parazitární kolonizace organismu analýzou střevního obsahu. Důležité bude propojení informací složení o stravy a parazitárních nákazách a zjištění zda a v jaké míře přispívalo složení potravy k parazitárním onemocněním.

Notes

Rezervováno pro studentku: Bc. Kateřina Novotná UČO 449475

Mitochondrial dynamics in pathogenesis of pediatric solid tumors

Supervisor: RNDr. Jan Škoda, Ph.D.

Mitochondria are highly dynamic organelles continuously changing their morphology between the fragmented globular and fused tubular mitochondrial network. Proper mitochondrial dynamics, mitochondrial fission and fusion, is essential for mitochondria homeostasis, as it is indispensable for both mitochondrial biogenesis and degradation of damaged mitochondria by mitophagy. Mitochondrial dynamics therefore affects a plethora of functions performed by mitochondria, including their crucial role in regulation of stem cell fate. Indeed, the dysregulation of mitochondrial dynamics and turnover has been associated with many human diseases, including cancer. However, molecular mechanisms driving the modulation of mitochondrial dynamics in cancer are still poorly understood. Limited information is also available on the role of mitochondrial dynamics and turnover in regulation of cancer stem cells in childhood cancers. Thus, the aim of this thesis is to elucidate the role of mitochondrial dynamics in drug resistance and cancer stemness in pediatric solid tumors. Using in vitro and in vivo models, it will be also assessed whether targeting mitochondrial dynamics may prevent the drug-induced resistance. These results will provide an important insight into the molecular mechanisms underlying the induction of therapy resistance in aggressive childhood cancers.

Notes

Téma je určeno pro Bc. Karolínu Bořánkovou (učo 451603). Školitelem práce bude RNDr. Jan Škoda, Ph.D. po schválení Vědeckou radou PřF MU.

Molecular characterization of phage-host interactions with impact on host phenotype

Supervisor: Mgr. Tibor Botka, Ph.D.

The increasing prevalence of antibiotic resistant staphylococcal strains, mostly in hospital environment, is a serious health problem. To fight infections that cannot be treated by established procedures, therapy based on bacterial viruses - phages that kill host bacteria can be used. Phages also have several other applications, including phage-derived enzybiotics with antibacterial effect. The aim of this thesis is to characterize interactions between lytic phages and their hosts with possible impact on effectiveness of therapy of infections caused by the host bacterium. Three topics will be solved, each with potential to be published in an impacted journal. Firstly, novel lytic phages will be described on molecular level, comparative genomics and transcriptomics will follow, and their growth properties will be determined. Secondly, antimicrobial enzymes of studied phages will be characterized and their suitability for the therapeutic use will be evaluated. The third topic will be focused on emergence of bacterial resistance to phages. During the PhD study, the student will have opportunity to cooperate with laboratories focused on staphylococcal research in the University of Tübingen. The student will be involved in work on present and future grant projects of the laboratory.

Notes

Školitelem práce bude jmenován Mgr. Tibor Botka, Ph.D. po schválení Vědeckou radou Přírodovědecké fakulty MU. Téma je určeno pro Jiřinu Havránkovou (UČO 489500).

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/. Téma je určeno pro Petera Macseka (UČO 451608).

Organization and evolution of plant chromosomes

Supervisor: RNDr. Terezie Mandáková, Ph.D.

Notes

Šklitelkou této práce bude paní dr. Mandáková po schválení Vědeckou radou PřF MU. Téma je určeno pro studentku Michaelu Kubovou.

Post-polyploid genome evolution in the mustard family (Brassicaceae)

Supervisor: RNDr. Terezie Mandáková, Ph.D.

Recurring polyploidization and post-polyploid diploidization (PPD) cycles have shaped genome evolution, speciation and cladogenesis in plants. The role of polyploidization and PPD in genome evolution of the selected Brassicaceae species will be addressed by high-quality genome and transcriptome sequencing and assemblies with the aim to (i) establish genomes structure of these species, (ii) specify intra- and inter-subgenome rearrangements, (iii) reveal patterns of gene fractionation and subgenome dominance, (iv) elucidate dynamics of transposable elements and small-scale genomic variations, and (v) employ phylogenomic approaches to date species divergences and polyploidization(s). The resulting findings will advance our understanding of post-polyploid genome evolution in plants.

Notes

Školitelkou práce bude dr. Terezie Mandáková, PhD. - po schválení Vědeckou radou PřF MU.

Proteins interactions with DNA, focus on local DNA structures

Supervisor: doc. 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.
Školitel: Doc. Mgr. Václav Brázda, PhD.; Biofyzikální ústav AVČR, Královopolská 135, 612 65 Brno, tel. 5 41517231, fax 5 41211293, e-mail: vaclav@ibp.cz

Notes

Téma je rezervováno pro studentku Veroniku Bosákovou.

Study of emergence of bacterial resistance to phages in staphylococci

Supervisor: doc. 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.

Study of guanine quadruplexes in the RNA genome of tick-borne encephalitis virus and elucidating their role in viral life cycle

Supervisor: Mgr. Luděk Eyer, Ph.D.

Disertační práce si klade za cíl identifikovat a charakterizovat guaninové kvadruplexy (G4) lokalizované v genomu viru klíšťové encefalitidy pomocí biofyzikálních, biochemických a (molekulárně) biologických metod. Pozornost bude zaměřena rovněž na studium antivirové aktivity (an)organických ligandů specificky se vázajících a stabilizujících G4, které představují novou generaci potenciálních terapeutik. Důležitým bodem bude selekce virových mutant nesoucích mutace v G4-lokusech (tzv. konformačně-specifické mutace) a charakterizace biologických vlastností takových mutantů in vitro i na myším modelu. Práce přinese cenné poznatky vedoucí k objasnění role G4 v replikačním cyklu viru a otevře nové možnosti antivirové terapie.

Notes

Školitelem práce bude: RNDr. Luděk Eyer, Ph.D., Výzkumný ústav veteriárního lékařství, v.v.i., Hudcova 70, 621 00 Brno (E-mail: eyer@vri.cz; Tel: 736 615 800) po schválení Vědeckou radou PřF MU.

TGF-beta in craniofacial osteogenesis - novel molecular aspects and interactions

Supervisor: prof. RNDr. Eva Matalová, Ph.D.

Téma je součástí projektu Inter-Action (spolupráce ČR-USA), který byl zahájen v roce 2020 a má za cíl výzkum molekulárních interakcí týkajících se TGF-beta signalizace se zaměřením na osteogenní markery. Základní výzkum s aplikačním potenciálem v oblasti regenerativní medicíny.

The molecular role of the prominin-1/CD133 protein in cancer cells

Supervisor: RNDr. Jan Škoda, Ph.D.

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.

Notes

Školitelem projektu bude dr. Jan Škoda po schválení Vědeckou radou PřF MU. Téma je určeno pro Petra Pleskače (učo 473885.

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/

Tumor-derived inflammatory factors and anti-tumor immunity in metastasis

Supervisor: Mgr. Lucia Knopfová, Ph.D.

Chronic inflammation and proinflammatory cytokines such as interleukin 1 are considered to be tumour promoting. However, successful cancer immunosurveillance is consistently associated with elevated local levels of proinflammatory cytokines. Inflamed, immunologically “hot” tumors are rich in infiltrating T-cells and provoke a strong response by the immune system. On contrary, tumor cells may benefit from mimicking local inflammation e.g. while exiting vasculature or awaking from dormancy. A growing body of evidence indicates that metastasis initiation may be the culmination of a highly fluid process involving transitional cellular states, dynamic interactions between clonal tumor populations, and both short-distance and long-range interactions between tumor cells and the host organs. Successful manoeuvring of tumor cell communities in perils of systemic versus local inflammation thereby qualifies them for efficient metastasis initiation. How tumor-driven inflammation incites or stupefies host cells or facilitates interclonal cooperation in different steps of metastatic cascade is thereby of interest not only in context of cancer immunotherapy.

Notes

Školitelkou práce bude jmenována Dr. Knopfová po schválení Vědeckou radou Přírodovědecké fakulty MU.

Utilizing CRISPR/Cas9 technology for the functional characterization of non-coding RNAs in glioblastoma multiforme

Supervisor: RNDr. Kamila Součková, Ph.D.

Velká část eukaryotického genomu je tvořena sekvencemi DNA, které jsou přepisovány do nekódujících RNA. Vedle intenzívně studovaných krátkých nekódujících RNA se jedná především o velkou, sekvenčně a funkčně rozmanitou a současně málo prozkoumanou skupinu dlouhých nekódujících RNA. Nekódující RNA hrají klíčové role v transkripčních a post-transkripčních regulačních drahách- Výsledky dosavadního bádání naznačují, že deregulace celé řady nekódujících RNA je úzce spojena s procesy provázejícími vznik a průběh nádorové bujení. Multiformní glioblastom je nejčastější primární nádor mozku astrocytárního původu. Prognóza pacientů s tímto onemocněním je i přes dostupnou konvenční terapii velmi nepříznivá. Studium funkce nekódujících RNA by mohlo vést k nalezení nových terapeutických cílů nebo diagnostických markerů a zlepšit tak celkovou prognózu pacientů s tímto fatálním onemocněním. Náplní doktorské práce bude vytypovat, experimentálně ověřit a popsat zapojení vybraných nekódujících RNA v signálních drahách souvisejících s maligní transformací u multiformního glioblastomu. K dosažení cíle bude využita bohatá škála molekulárně biologických metod včetně metodiky CRISPR/Cas9.

Notes

Téma je vypsáno pro Bc. Mateje Jasíka. Vedoucím práce bude RNDr. Kamila Součková, Ph.D. po schválení vědeckou radou PřF MU.

Study information

Provided by Faculty of Science
Type of studies Doctoral
Mode full-time Yes
combined Yes
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 Czech
Doctoral board and doctoral committees

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