Genomics and Proteomics

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Přijímací řízení do doktorských programů - akad.rok 2020/2021 (zahájení: jaro 2021)
Submission deadline until midnight 30 Nov 2020

What will you learn?

The aim of the Genomics and Proteomics program is to train top class specialist in these subjects. Students will acquire extensive and in-depth knowledge about the structure and function of the genome at all basic levels of living systems ( i.e., the viral genome, the genome of bacteria, protozoa, fungi and yeasts, algae, higher plants, animals and human genome in more detail). They will deepen their knowledge and skills in basic biological disciplines (especially genetics, molecular biology, microbiology, immunology, biostatistics, physiology of organisms), in biochemistry and proteomics (general biochemistry, enzymology, biochemical proteomic methods) and in biophysics (biophysical methods).

In addition to the theoretical principles of the discipline, students are also closely acquainted with performing basic and advanced methods used in various disciplines. Graduates of this field of study will find jobs in various fields: particularly in research focused on the analysis of genomes (basic research as well as applied research), in bioinformatics (including evolutionary aspects), in the field of molecular medicine (cancer, familial and hereditary diseases, gene therapy), in genetic engineering of microorganisms, plants, and animals, in the development of new biotechnologies, in pharmacogenomics, and in analyzing the proteome of individual groups of organisms, including humans.

Practical training

Students conduct their research activities in the laboratories of their supervisors, where they acquire practical skills essential for their research topics. Further practical skills can be acquired via collaborative frameworks of their labs (either in Czech Republic or abroad).

Further information

http://www.sci.muni.cz/en/DoktorskeStudium/Prehled-programu-a-oboru/obor/Genomika-a-proteomika

Career opportunities

Graduates of this doctorate program are qualified to run a research activities at research institutions and biotech companies, and teach at universities. They will find jobs in various fields, particularly in research focused on the analysis of genomes (basic research as well as applied research), on bioinformatics, molecular medicine, genetic engineering of microorganisms, plants, and animals, on the development of new biotechnologies, and on the analysis of the proteome of individual groups of organisms. In wider sense, they can conduct research and research-related activities like experimental work, project management, etc.

Admission requirements

During the admission interview, the general knowledge of the candidate is examined, as well as the motivation and knowledge in the area of the topic for which the candidate is applying. The ability to communicate in English is verified by the applicant briefly presenting his / her current professional experience (eg master thesis). To be accepted, the applicant must obtain a min. 180 out of a total of 300 points: 1. expert knowledge 60 points / 100 2. language skills 60 points / 100 3. formal criteria 60 points / 100

Application guide

Deadlines

1 Aug – 30 Nov 2020

Submit your application during this period

Submit an application

Supervisors and dissertation topics

Supervisors

Dissertation topics

Single-subject studies

Identification and quantification of N-linked glycoproteins presented in sera and tissues of patients with oncological disease

Supervisor: prof. Ing. Lenka Hernychová, Ph.D.

Je známo, že změny glykanových struktur na povrchu nádorových buněk ovlivňují proliferaci, adhezi, migraci i buněčnou signalizaci. Strukturně změněné N-glykany (zvýšená fukosylace, sialylace nebo přítomnost komplexních rozvětvených struktur) byly detekovány v sérech a nádorových tkáních pacientů s různými typy nádorů. Proto glykoproteiny i jejich glykanové části jsou atraktivními markery vhodnými pro diagnostiku onkologických onemocnění.
Cílem dizertační práce bude podílet se na vývoji metod izolace glykoproteinů ze sér a tkání pacientů s nádorem vaječníků nebo nádorem prsu s využitím hydrazidové chemie nebo lektinové chromatografie. Analýza připravených vzorků na hmotnostních spektrometrech, hodnocení dat, selekce markerů a jejich diskuze s dostupnou literaturou.

Doporučená literatura
Zhang H, Li XJ, Martin DB, Aebersold R. Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nat Biotechnol. 2003 Jun;21(6):660-6. PMID:12754519

Hernychová L, Uhrík L, Nenutil R, Novotný MV. Glycoproteins in the Sera of Oncological Patients. Klin Onkol. 2019 Fall;32(Supplementum 3):39-45. PMID:31627705

Mechanisms of effect of LDL receptor genetic variants

Supervisor: Mgr. Lukáš Tichý, Ph.D.

Our workgroup is interested in molecular basis of severe dyslipidemias in human. The most common of dyslipidemias is familial hypercholesterolemia (FH). The frequency of FH in most populations is about 1/200, and so it is possible to predict that about 50,000 people could be affected in the Czech Republic. The clinical phenotype of FH is caused predominantly by mutations in the LDLR gene. LDLR mutations have been reported along the whole length of the gene. Our workgroup focuses on functional assays of LDLR mutations. For further details please refer to our publications (PMIDs: 27175606, 20663204, 28379029, …).

Modeling Small RNA binding rules using Machine Learning

Supervisor: Panagiotis Alexiou, PhD

Small RNAs (miRNAs, piRNAs) bind their targets in a sequence and structure dependent manner. The rules of binding for each category of small RNAs have been studied for a long time, but have not to date been clearly identified.

New technological advancements in the fields of Sequencing have allowed the production of 'chimeric' reads that contain both the small RNA and a part of the binding site sequence. Using these type of datasets we can, for the first time, have an unbiased prediction of where small RNAs bind on their targets.

Deep Learning is a field of Machine Learning that has shown great advances in the past decade by using Deep Neural Networks to model complex datasets. In the field of Genomics, it is being increasingly used to identify RNA binding protein sites, Transcription Factor Binding Sites etc.

We will utilize Deep Learning techniques and NGS datasets of small RNA binding to model and interpret the rules of small RNA binding to their targets.

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 [1] or G-quadruplex binding properties [2]. Contemporary we have developed easy accessible web tools for analyses of inverted repeats [3] and G-quadruplexes[4] and we have analyzed the presence of inverted repeats and G-quadruplexes in various genomic datasets, such as all sequences mitochondrial genomes [5], all bacterial genomes [6], in S.cerevisiae (in review), 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.

Proteins involved in the regulation of telomeric repeats

Supervisor: Mgr. Petra Procházková Schrumpfová, Ph.D.

Telomeres are the physical ends of linear chromosomes that protect these ends against erroneous recognition as unrepaired chromosomal breaks and regulate the access to Telomerase, a reverse transcriptase that solves the problem terminal DNA loss in each cell cycle. Telomeric structures are known to be composed of short repetitive DNA sequences (telomeric repeats), histone octamers, and number of proteins that bind telomeric DNA, either directly or indirectly, and together, form the protein telomere cap.

Interestingly, telomeric repeats are not exclusively located at the chromosome ends, but they belong among cis-regulatory elements present in promoters of several genes. The distribution of short telomeric motifs (telo-boxes) within the genome is not random, and proteins associated with these telomeric repeats may serve as the epigenetic regulatory mechanisms facilitating metastable changes in gene activity.

The telomeric cap proteins of diverse organisms are less conserved than one might expect. In plants, knowledge of telomere-associated proteins associated with telomeres and regulation of access to telomerase complex is incomplete. The research aims to elucidate the roles of candidate proteins involved in telomerase biogenesis in plants. The outcomes contribute to the characterization of new telomere- or telomerase-associated proteins, complete our knowledge of telomerase assembly or telomere maintenance in plants. In addition, we would like to examine the regulatory factors associated with the telo-boxes present in promoters of the genes active during plant development.

Notes

Poznámky: Práce může být vypracována ve slovenštině či angličtině.

Qualitative and quantitative analysis of selected types of posttranslational modifications

Supervisor: prof. RNDr. Zbyněk Zdráhal, Dr.

V rámci mého doktorského studia bych se chtěla věnovat analýze posttranslačních modifikací (PTM). Posttranslační modifikace (PTM) významně ovlivňují regulaci buněčných procesů. V současné době je známo více než 400 druhů. Analýza PTM je poměrně složitý proces, jelikož neexistuje jedna univerzální metoda, která by byla schopná detekovat všechny druhy PTM současně, a zpravidla je nutno použít pro každý druh modifikace individuální postup přípravy vzorku, resp. metodu analýzy. Navíc modifikovaných forem proteinů je v rámci proteomu kvantitativně řádově méně než odpovídajících nemodifikovaných proteinů, což také znesnadňuje jejich detekci.

Cílem disertační práce bude vývoj a optimalizace souboru metod pro kvalitativní a kvantitativní charakterizaci vybraných typů posttranslačních modifikací hmotnostní spektrometrií a aplikace těchto metod v rámci řešení probíhajících projektů.

Experimentální část bude probíhat v laboratořích VS/CL Proteomika, CEITEC-MU (budova A26, UKB Bohunice), vybavených špičkovou instrumentací.

Notes

Před podáním přihlášky je nutno se neformálně seznámit s tématem, kontaktujte prof. Zbyňka Zdráhala.

Regulation of transposons in dioecious plants

Supervisor: RNDr. Roman Hobza, Ph.D.

Transpozony jsou mobilní genetické elementy schopné samostatné replikace v rámci genomů většiny organismů. Transpozony mohou být domestikovány, podílejí se na tvorbě funkčních strukur genomů a genových regulačních sítí, ale jejich inzerční aktivita může způsobovat škodlivé mutace. Pro přežití hostitele je proto důležitá existence mechanizmů bránících nadměrné aktivitě transpozonů. Tyto obranné mechanizmy jsou založeny především na RNA interferenci (RNAi) využívající krátké molekuly RNA (sRNA) k cílenému umlčení transpozonů na transkripční (epigenetické modifikace chromatinu) nebo posttranskripční úrovni. U dvoudomých rostlin byly objeveny transpozony s velmi odlišnou distribucí na pohlavních chromozomech, což naznačuje, že jsou transpozony různě aktivní v samčí a samičí linii. Předmětem doktorské práce je charakterizace repetitivních sekvencí a transpozonů u vybraných dvoudomých rostlin a následně studium mechanizmů regulujících aktivitu transpozonů. Doktorská práce předpokládá zvládnutí širokého spektra metod molekulární biologie a cytologie, přípravu transgenních a mutantních rostlin, práci s tkáňovými kulturami, zvládnutí mikroskopických technik a analýzy obrazu, některých bioinformatických nástrojů a práci s odbornou literaturou. Výsledky budou prezentovány formou plakátových sdělení nebo přednášek na mezinárodních konferencích a článků v impaktovaných časopisech.

Structural Maintenance of Chromosomes (SMC) complexes

Supervisor: doc. Mgr. Jan Paleček, Dr. rer. nat.

Our lab is interested in the chromatin structure and dynamics. The chromatin structure must be not only maintained through the cell cycle, but also dynamically modulated during processes like mitosis and replication. Amongst the chromatin-associated complexes, the SMC (Structural Maintenance of Chromosomes) complexes play the central role. Two of them, Cohesin and Condensin, facilitate chromosome segregation and condensation, respectively. Third, the most enigmatic SMC5/6 complex is involved in the DNA damage repair and replication restart, however its essential chromatin-modulating function is still unclear. Our laboratory focuses on the SMC5/6 architecture and functions using state-of-the-art structural biology approaches and various molecular biology tools. For further details please refer to our website (http://www.ncbr.muni.cz/SPEC/) and our publications (https://orcid.org/0000-0002-6223-5169).

Structure-functional relationship of telomeres and telomerases

Supervisor: Mgr. Eva Sýkorová, CSc.

In brief, intracellular life of telomerase is linked to processes of telomerase biogenesis, action at telomeres and degradation. During these processes telomerase interacts with many protein partners that might be essential for particular steps. Highly dynamic nature of telomerase interactome causes difficulty in uncovering functions of telomerase partners that are important for telomerase and those unrelated to telomerase. Using classical experimental methods as well as genomics and proteomics approaches accompained with in silico analyses, we study structure-functional relationship of telomeres and telomerases.

Telomere biology

Supervisor: prof. RNDr. Jiří Fajkus, CSc.

This research direction includes the structure, evolution and maintenance of telomeres and their roles in chromosome stability, DNA repair and plant speciation
Further we investigate epigenetic mechanisms in the regulation of gene expression, chromatin assembly, genome stability and telomere homeostasis. Biochemical, bioinformatic and molecular biology approaches are applied in this research.
For more details, see our web pages: https://www.ceitec.eu/chromatin-molecular-complexes-jiri-fajkus/rg51

Tumor biology

Supervisor: doc. Mgr. Roman Hrstka, Ph.D.

Notes

Před podáním přihlášky je vhodné se seznámit s konkrétními tématy pro daný kalendářní rok. Kontakt: doc. Hrstka, MOÚ, Brno.

Y chromosome epigenetic degeneration in dioecious plant Silene latifolia

Supervisor: José Luís Rodríguez Lorenzo, Ph.D.

Silene latifolia is a model organism to study evolutionary young heteromorphic sex chromosomes in plants. S. latifolia sex chromosomes are formed by several regions with ongoing recombination suppression. This recombination suppression triggers Y-allele gene degeneration through accumulation of mutations, chromosome rearrangements and transposable element (TE) insertions. It is known that epigenetic processes can be involved in both gene degeneration and TE regulation. Recent research on maize TEs indicated a new player in TE mobility regulation. This new regulator is another cytosine modification called 5-hydroxymethylcitosine (5-hmC). We aim to analyze methylation and hydroxymethylation of the different TE families and the quantification of these modifications in both sex chromosomes in both sexes separately. We will provide important information about sex chromosome evolution and degeneration processes in plants.

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
Collaborating institutions
  • The Czech Academy of Sciences
  • Biofyzikální ústav AV ČR
Doctoral board and doctoral committees

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