Biomolecular chemistry and bioinformatics

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

What will you learn?

The study program Biomolecular chemistry and bioinformatics includes knowledge about the structure of biologically important bio(macro)molecules (proteins nucleic acids, oligosaccharides, etc.), and the relation between their structure and biological function. Students are trained in methods of carrying out and applying research on the 3-D structure and function of bio(macro)molecules. The technical facilities allow students regular use of the most modern methods, both experimental (nuclear magnetic resonance, x-ray diffraction, cryo-electron microscopy, methods in biomolecular interactions studies , methods of molecular biology) and computational (quantum chemistry, molecular mechanics and dynamics). Emphasis is placed on independent work by students in the context of implementing research projects, including the ability to communicate and present results in the English language. Students also learn to make use of information available in literature and electronic databases. The range of specialized lectures allows students to deepen their theoretical knowledge.

Study covers the following research areas:

Computational chemistry and chemoinformatics

Structural bioinformatics

Structural analysis using nuclear magnetic resonance, x-ray difraction and cryo-electron microscopy

Glycobiochemistry

Interaction of proteins with cell membrane

Structural virology

Structure and dynamics of nucleic acids

Structural biology of gene regulation

Non-coding genome

RNA quality control

Recombination and DNA repair

DNA sequence analysis

Next-generation sequencing

The program of studies is designed to be interdisciplinary, helping students learn to combine knowledge from various fields.

Practical training

No information available

Further information

http://ncbr.muni.cz

Career opportunities

The goal of the doctoral study programme is to prepare specialists at the highest level who will be not only specialists with detailed knowledge of certain techniques, but creative thinkers with a broad overview of the field of biomolecular chemistry and bioinformatics with good foundations in theory. Although the graduate will be qualified mainly for an academic career, he will also be a specialist capable of serving in the commercial sphere, especially in biochemical and pharmaceutical research, working with biologically-oriented databases, and in fields using advanced methods of computational chemistry and bioinformatics. As the experience of the past few years has shown, foreign contacts and study stays can help the graduate to find work at the top institutes abroad. Foreign contacts and study stays can help the graduate to find work at the top institutes abroad.

Admission requirements

The admission procedure evaluates expert knowledge (max. 100 points) and language skills (max. 100 points). For admission, the candidate must obtain at least 160 points. The candidate should consult his/her potential supervisor before submitting application.

Criteria for evaluation

No information available

Application guide

Deadlines

1 Jan – 30 Apr 2020

Submit your application during this period

Submit an application

Supervisors and dissertation topics

Supervisors

Dissertation topics

Single-subject studies

Inhibition of DNA repair nucleases – from biological probe to cancer therapy

Supervisor: doc. Mgr. Lumír Krejčí, Ph.D.

We invite applications for a PhD studentship from applicants with an enthusiastic interest in molecular biology and biochemistry. The successful candidate will work under the supervision of Dr. Krejčí to identify and characterize novel inhibitors of DNA repair nucleases, their mechanisms of action and therapeutic implications.

The PhD position candidate should hold or be about to complete a Masters degree in molecular biology, biochemistry or similar field. The applicant is also expected to demonstrate essential training in a range of molecular biology techniques relevant to basic research, should be well-organised, motivated and passionate about pursuing a career in biomedical research.

We offer fully funded positions with competitive salary in a well established laboratory. The lab hosts international team members, has a strong publication track record and international collaborations. The offered projects contribute to a rapidly advancing, very competitive field. The successful candidate can start immediately.

Mechanism of action of antimicrobial peptides

Supervisor: doc. RNDr. Robert Vácha, PhD.

OBJECTIVES: The aim is to elucidate the relationship between molecular properties of amphiphilic peptides and their ability to translocate and form transmembrane pores in membranes with various lipid compositions. The obtained understanding will be used for the development of new antimicrobial peptides, which can serve as a new type of antibiotic drugs.



DESCRIPTION: Antibiotic-resistant bacteria cause more than 700 000 deaths per year, and the forecast is 10 million per year in 2050. Moreover, emerging strains of bacteria resistant to all available antibiotics may lead to a global post-antibiotic era. Because of this threat, the WHO and the UN are encouraging the research and development of new treatments. Antimicrobial peptides are promising candidates for such new treatments. We will study the molecular mechanism of action of antimicrobial peptides and determine the critical peptide properties required for membrane disruption via the formation of transmembrane pores and spontaneous peptide translocation across membranes. Based on the obtained insight, we will design new peptides and test their abilities. The most effective peptides will be evaluated for antimicrobial activity and human cell toxicity using growth inhibition and hemolytic assays, respectively. Student(s) will master tools of computer simulations, in particular, molecular dynamics techniques and methods to calculate free energies. Moreover, he/she will learn the advantages and disadvantages of various protein and membrane parameterizations, including all-atom and coarse-grained models. The simulations will be complemented by in vitro experiments using fluorescent techniques.



EXAMPLES of potential projects: * Antimicrobial peptides and formation of membrane pores * Synergistic mechanisms between antimicrobial peptides * Membrane disruption by antimicrobial peptides in non-equilibrium conditions



MORE INFORMATION about the group: vacha.ceitec.cz



PLEASE NOTE: before the formal application process, all interested candidates should contact Robert Vacha (robert.vacha@mail.muni.cz).

Protein Affinity and Selectivity to Cellular Membranes

Supervisor: doc. RNDr. Robert Vácha, PhD.

OBJECTIVES: The aim is to elucidate the relationship between protein sequence and preferred composition and curvature of human membranes,i.e., find peptide motifs that are selective to specific membranes in cells (plasma membrane, endoplasmic reticulum, Golgi apparatus, mitochondria, etc.). The obtained understanding will be used for the development of new protein biomarkers, sensors, scaffolds, and drugs.



DESCRIPTION: The control of biological membrane shape and composition is vital to eukaryotic life. Despite a continuous exchange of material, organelles maintain a precise combination and organization of membrane lipids, which is crucial for their function and the recruitment of many peripheral proteins. Membrane shape thus enables the cell to organize proteins and their functions in space and time, without which serious diseases can occur. Moreover, membrane curvature and lipid content can be specific to cancer cells, bacteria, and enveloped virus coatings, which could be utilized for selective targeting. We will develop a new method, using which we will elucidate the relationship between the protein sequence and the preferred membrane. The relationship will lay the foundations for the design of new protein motifs sensitive to membranes with a specific curvature and composition. Student(s) will master tools of computer simulations, in particular, molecular dynamics techniques and methods to calculate free energies. Moreover, he/she will learn the advantages and disadvantages of various protein and membrane parameterizations, including all-atom and coarse-grained models.



EXAMPLES of potential projects: * Determination of helical motifs for specific membrane compositions * Development of implicit membrane model for fast determination of protein-membrane affinity * Helical peptides and their sensitivity for membrane curvature



MORE INFORMATION: vacha.ceitec.cz



PLEASE NOTE: before the formal application process, all interested candidates should contact Robert Vacha (robert.vacha@mail.muni.cz).

Protein Structure and Dynamics

Supervisor: prof. Mgr. Lukáš Žídek, Ph.D.

The research goal is investigation of structure, dynamics, and biologically relevant properties of proteins, using NMR spectroscopy and other high-resolution approaches. Currently, our group is mostly interested in studies of molecular motions using NMR relaxation and relaxation dispersion; in studies of protein disorder using NMR approaches providing sufficient resolution (usually based on non-uniformly sampled high-dimensional spectra); and in studies of interactions of intrinsically disordered proteins with their binding partners (using NMR, cryo-EM, and biophysical methods). The systems currently studied in the laboratory include bacterial RNA polymerases and microtubule associated proteins.

We are inetrested structure and dynamics of well-ordered and domains of subunits and sigma factors of RNA polymerase from B. subtilis, characterization of structural features and dynamics of disordered domain, and in importance of electrostatic interactions for structural properties and biological function of the protein. Currently we extend our interest to mycobacterial RNA polymerase.

Microtubule associated protein 2c (MAP2c) is a key factor regulating microtubule dynamics in developing brain neurons, and an example of an intrinsically disordered proteins with an important physiological function and detectable structure-function relationship. The first goal is to study MAP2c in a natural complexity and by methods providing atomic resolution. Such methods include paramagnetic relaxation interference, to detect and describe transient local structures of MAP2c important for its function, and real-time NMR, to monitor kinetics of MAP2c phosphorylation by relevant kinases of different signalling pathways. The second goal is to characterize interactions of MAP2c with biologically important binding partners, especially with isoforms and a monomeric form of regulatory protein 14-3-3. The third goal is to test the effect of cellular environment on MAP2c by recording NMR spectra at near-to-native conditions (in cells and/or cell lysates) and/or by performing cryo-electron tomography on monolayered neurons.

EXAMPLES OF POTENTIAL PHD TOPICS:
  • Interactions underlying physiological function of Microtubule Associated Protein 2c
  • Structure, dynamics and interactions of bacterial RNA polymerase subunits and sigma factors

Simultaneous gene transcription and translation in bacteria

Supervisor: Mgr. Gabriel Demo, Ph.D.

OBJECTIVES: The research aims to unravel the fundamental mechanism of the transcription-translation coupling in bacteria. These studies will significantly advance the current understanding how the lead ribosome closely trails the RNA polymerase (RNAP), thus promoting pause-free transcription, mRNA quality and efficient gene expression in bacteria.

FOCUS: Doctoral research projects focus on the mechanistic details and functional outcomes of coupled transcription-translation in bacteria. Students benefit from the shared cutting-edge core facilities of CEITEC that include (i) X-ray crystallography – crystallization robot Mosquito, Rigaku crystal hotel and diffraction system, (ii) cryo-EM equipment - Versa 3D dual beam microscope, Titan Krios and F20 electron microscopes (iii) High-field NMR systems, and (iv) biomolecular interactions equipment - confocal microscopes, near-field optical microscope (SNOM), surface plasmon resonance, microcalorimetric equipment.

EXAMPLES of potential student doctoral projects:

  • Structural and functional identification of factors required to couple transcription and translation in bacteria
  • Structal studies of various states of direct and bridged transcription-translation coupling in vitro and in vivo

PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact Gabriel Demo (gabriel.demo@ceitec.muni.cz) for informal discussion. MORE INFORMATION:https://www.ceitec.eu/structural-biology-of-coupled-transcription-translation-gabriel-demo

Structural dynamics, function and evolution of RNA and DNA. From the origin of life to modern biochemistry.

Supervisor: prof. RNDr. Jiří Šponer, DrSc.

Our scientific goal is understanding of the most basic principles of structural dynamics, function and evolution of DNA and RNA.

Our methods are:
  • Classical Molecular Dynamics (MD) simulations
  • Quantum-chemical (QM) method
  • Hybrid quantum-classical (QM/MM) methods, quantum molecular dynamics
  • Structural bioinformatics
Specific experiments are possible in the field of prebiotic chemistry in collaborating laboratories - need to discussed. Modern computations are extensively combined with many experimental techniques (NMR, X-Ray, high-energy lasers, biochemical techniques) mostly via numerous collaborations. We collaborate with 30 foreign and Czech laboratories. We publish about 20 papers annually and belong to the most cited Czech research groups. See the full list of papers on this web page. We have excellent in-house computer facilities, which are regularly upgraded. We currently work in several mutually interrelated research areas.
  • RNA structural dynamics, folding and catalysis
  • Protein-RNA complexes
  • DNA, with focus on G-quadruplexes
  • Diverse types of quantum-chemical studies on nucleic acids systems

Origin of life (prebiotic chemistry), i.e., creation of the simplest chemical life on our planet (or anywhere else in the Universe), with a specific attention paid to the formamide pathway to template-free synthesis of the first RNA molecules. This specific project includes also in house experimental research. Besides studies of specific systems, we are also involved extensively in method testing/development, mainly in the field of parametrization of molecular mechanical force fields for DNA

NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact Prof. Jiri Sponer (sponer@ncbr.muni.cz) for an informal discussion.

Laboratory web page https://www.ibp.cz/en/research/departments/structure-and-dynamics-of-nucleic-acids/info-about-the-department

List of publications https://www.ibp.cz/en/research/departments/structure-and-dynamics-of-nucleic-acids/publications

Study of molecular details of DNA repair and its role in cancer

Supervisor: doc. Mgr. Lumír Krejčí, Ph.D.

Naše laboratoř se zaměřuje na studium molekulární podstaty zhoubných onemocnění, které souvisí s rekombinací a opravou poškozené DNA. DNA obsažená v lidské buňce je neustále poškozována vnějšími i vnitřními vlivy (radiace, UV záření apod.) Různých poškození nebo zlomů v DNA je až půl milionu za den. Zvláště zlomy DNA vedou k nestabilitě genomu a mohou mít za následek zhoubné změny například vyvolání rakoviny. Jedním z mechanismů, který zaručuje bezchybnou opravu poškozené DNA je homologní rekombinace. Pro tento ročník vypisujeme jedno místo na některé z následujících témat. 1)RecQ4/RecQ helikáza, mutována u „Rothmund-Thomson Syndromu“, a její biochemická charakterizace. 2)Úloha Srs2 proteinu při opravě poškozené DNA. 3)„Bloom Syndrom“ protein a jeho role při odstraňování nebezpečných produktů. 4)Rad51 rekombinasa a co ji ovlivňuje. Při řešení těchto úkolů se zájemci seznámí s molekulárně biologickými, biochemickými, strukturálními a genetickými metodami.

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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