Structural Biology

Structure is function – Revealing the hidden machinery of a cell

Programme specification

General information

Structural Biology is a modern interdisciplinary and significantly methodologically focused study programme offering a possibility to study the structure and function of biologically active macromolecules – proteins, nucleic acids and their functional complexes.

It is open for graduates of Master's study programme with knowledge in the fields of biochemistry, biophysics, molecular biology, physical chemistry, pharmacology and related fields and enables students to develop research skills and socio-managerial competence by arranging their studies and selecting lectures according to their field of interest. Students will acquire the necessary methodological skills and knowledge to study the molecular structure of the essential components of living systems and will gain the socio-managerial competence in Life Sciences.

The goals of structural biology include developing a comprehensive understanding of the molecular shapes and forms embraced by biological macromolecules and extending this knowledge to understand how different molecular architectures are used to perform the chemical reactions that are central to life.

Central tools used in this research include X-ray diffraction, nuclear magnetic resonance (NMR), cryo-electron microscopy (cryo-EM), other spectroscopies and biophysical methods, protein expression, biophysical and bioorganic chemistry, computer science and bioengineering.

The programme brings together human and material resources of Masaryk University and Mendel University.

Experts of the research programme Structural Biology at the Central European Institute of Technology (CEITEC) transmit to students their unique experience in major areas of the field (NMR, cryo-EM, Glycobiochemistry, bioinformatics, computational chemistry, structure of proteins and nucleic acids).

The introductory part of the study is focused on deepening theoretical and practical knowledge. In parallel, each student will review the literature on the topic of their doctoral thesis. The essence of students' activity is focused on their own scientific projects. Students are taught to work independently and encouraged to process experimental data in methodologically relevant manners. An integral part of the study is a comprehensive interpretation of the obtained data and subsequent presentation of novel results by various means (presentation before the scientific community at professional forums, preparation of a poster and a scientific article).

Owing to an exceptionally high quality of the research infrastructure, the students of Structural Biology can apply a wide range of methods with different spatial and time-related resolution (e.g. single crystal X-ray diffraction, nuclear magnetic resonance, cryo-electron microscopy and tomography, etc.), and thus gain experience in the evaluation and interpretation of the measured data. Moreover, the students get insight into functional assays and gain practical experience, often based on in-vitro studies, using a variety of molecular biology, biochemistry and biophysics methods. Last but not least, they learn how to use complementary theoretical information obtained by provided computational methods, chemoinformatics, and bioinformatics

A successful graduate is able to

  • have profound theoretical knowledge in the field of functional and developmental biology and be aware of all aspects and current trends in the area
  • independently propose and solve important scientific projects from various fields of Life Sciences
  • manage a wide variety of laboratory methods as well as techniques of instrumental analysis of biological samples
  • design a wide scope of creative activities, plan and acquire resources for their implementation
  • propose and utilise advanced research methods using a broad spectrum of methods with different spatial and time-related resolution - single-crystal X-ray diffraction, nuclear magnetic resonance, cryo-electron microscopy and tomography etc.
  • evaluate and interpret results obtained by various methods of molecular biology, biochemistry and biophysics, and derive reasoned conclusions from their findings
  • use modern information technologies to acquire and process scientific information from the world electronic databases, to collect and process data online, to test the validity of models
  • join the international research teams in the field of Life Sciences
  • handle own findings in English language, not only in the form of writing a scientific paper, but also presenting and discussing with scientific capacities worldwide

Additional information

Detailed information regarding studies at MU and this particular programme is available here

http://ls-phd.ceitec.cz/

https://www.sci.muni.cz/student/phd/doporuceny-pruchod-studiem

Graduate destination

Graduates in Structural Biology, a modern field of study, have a wide range of opportunities in various fields of biomedicine and biotechnology-oriented companies, and in case of fundamental research in academic institutions as well. Knowledge of the spatial arrangement of biomolecules, their behaviour and function in living systems is the basis for defining their roles in physiological as well as pathological processes in living organisms, and therefore it is in research focus of many world-famous scientific teams. An innovative approach to teaching along with highly qualified and current curriculum is the best prerequisite for the smooth integration of graduates in major international research teams.

Admission Requirements

Requirements are specified in detail at http://ls-phd.ceitec.cz/information-for-applicants/ The admission procedure is carried out in two rounds. The first round is based on the application and background information - only complete applications with all mandatory parts will be accepted and reviewed. The applicants selected for the next round will be invited for the admission interview with the committee.

Evaluation criteria

Knowledge in the field of Life Sciences, communication in English, supplied materials and general impression.

Dissertation topics

Interaction Protein-Protein and Protein-Membrane

Supervisor: doc. RNDr. Robert Vácha, PhD.

EXAMPLES OF POTENTIAL PHD TOPICS:

  • Association of proteins in phospholipid membranes
A large fraction of membrane proteins form oligomers. These include receptors, ion channels, and fusion proteins, which association and dissociation control essential cellular processes. In the past, the membrane was viewed as a passive environment in which the association takes place. Now we know that membrane lipids can play an active role in determining the change of the oligomerization state. However, the interplay between the lipids and protein oligomerization state remains poorly understood. The goal of the PhD project is to calculate the association of selected membrane proteins in environments of various lipid compositions and determine the key features controlling the oligomerization state. We will do so by Molecular dynamics simulations with free energy calculations.
  • Selectivity of translocation across lipid membranes
We have shown that a specific class of transmembrane proteins, called scramblases, can facilitate not only spontaneous flip-flop of lipids but also a translocation of other amphiphilic molecules across cellular membranes. However, we miss information about the selectivity of this transport. The goal of the PhD project is to determine specificity of scramblase activity and obtain a molecular understanding of the selectivity. The main tool will be Molecular dynamics simulations with free energy calculations.

Candidates should have experience with simulations of membranes and proteins or free energy calculations

PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor and phd@ceitec.muni.cz

MORE INFORMATION: http://ls-phd.ceitec.cz/http-ls-phd-ceitec-cz

http://vacha.ceitec.cz/jobs-openings/

RNA as a drug target

Supervisor: Mgr. PharmDr. Peter Lukavsky, Dr. rer. nat.

RNA is an attractive drug target with enormous potential for future treatment of systemic and cancer-related pathologies. Yet, most of the currently applied and developed small molecule therapeutics for cancer and systemic diseases target proteins. Interestingly, from 20000 human protein-coding genes (1.5% of the human genome) only 2000-3000 genes are considered to be disease-related. In this context, small molecule drug therapies target less than 700 genes which represents less than 0.05% of the genome. While the portion of protein-coding information in the genome is minor, the ENCODE consortium has proposed that more than 75% of our genome is transcribed into RNAs. This also includes large non-coding regions of mRNAs, namely 3’UTRs which contain many regulatory elements important for spatio-temporal regulation of gene expression, such as translational control, RNA transport and localization and mRNA decay. We propose to target non-coding mRNA elements with small molecules to alter gene expression. We will focus on cancer-related genes, where protein targets often lack druggable elements and therefore targeting them on the mRNA level is an attractive alternative. Our research aims to identify functional mRNA motifs that can bind small molecules and to reveal common small molecule scaffolds which interact with similar 3D RNA structures and thus form a basis for rational lead optimization.

We are looking for highly motivated PhD candidates with background in biochemistry and biophysics who share our fascination for RNAs regulating gene expression.

PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor and phd@ceitec.muni.cz

MORE INFORMATION: http://ls-phd.ceitec.cz/http-ls-phd-ceitec-cz

https://www.ceitec.eu/rna-based-regulation-of-gene-expression-peter-lukavsky

Simultaneous gene transcription and translation

Supervisor: Mgr. Gabriel Demo, Ph.D.

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

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:

  • Determination of structural mechanism of coupled viral transcription and host translation in virus infected mammalian cells
  • 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: http://ls-phd.ceitec.cz/http-ls-phd-ceitec-cz

https://www.ceitec.eu/structural-biology-of-coupled-transcription-translation-gabriel-demo

Structural Analysis of Proteins

Supervisor: RNDr. Mgr. Jozef Hritz, Ph.D.

EXAMPLES OF POTENTIAL PHD TOPICS:

1. Structural characterization of hybrid proteins involved in neurodegenerative diseases

The hybrid proteins contains both structured and disordered regions of considerable lengths. Disordered region is often involved in the regulation of their enzymatic activity. The aim of this PhD project will be structural characterization of disordered region within the selected hybrid proteins having medicinal relevance. The structural properties will be studied by combination of solution NMR spectroscopy and computational simulations. Finally, the impact of phosphorylation on the interaction with client proteins will be evaluated by biophysical interaction techniques.

2. Structural properties of human carbonic anhydrase IX and design of its inhibitors

Carbonic anhydrase (CA) IX is cellular surface protein that in contrast to another isoforms in healthy condition is present mostly in gastrointestinal tract. However, it is highly upregulated in the cancer cells adapting to the extracellular environment while maintaining physiological conditions inside the cancer cell. The main aim of this PhD project is to characterize structural changes of CA-IX reflecting pH changes by NMR spectroscopy. It will also involve a computational design of inhibitors of CA-IX. Finally, their binding affinity will be experimentally verified by biophysical interaction methods.

PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor and phd@ceitec.muni.cz

MORE INFORMATION: http://ls-phd.ceitec.cz/http-ls-phd-ceitec-cz

https://www.ceitec.eu/protein-structure-and-dynamics-lukas-zidek

Structural Biology of WNT Signalling

Supervisor: Konstantinos Tripsianes, Ph.D.

We apply structural biology methods in order to gain a mechanistic view of CK1Epsilon action in the Wnt signaling pathways. CK1Epsilon represents an attractive therapeutic target but currently two key steps in the CK1Epsilon-mediated Wnt signal transduction are unclear: how CK1Epsilon gets activated and/or engages target proteins in response to Wnt signal and how CK1Epsilon phosphorylates its key substrate Dishevelled (DVL).

Our preliminary data suggest that we can efficiently apply methods of integrated structural biology to (i) probe the DVL conformational landscape using in vitro and in vivo FRET sensors coupled to SAXS and CryoEM, (ii) understand the (auto)phosphorylation regulatory mechanisms of CK1Epsilon, (iii) analyse by NMR the functional consequences of DVL phosphorylation and (iv) monitor DVL phosphorylation by real-time NMR under controlled cellular conditions. The position is part of a multidisciplinary project that combines (i) cellular and molecular biology, (ii) proteomic analysis, (iii) biochemistry and structural biology, and received generous funding in a very competitive grant scheme.

PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor and phd@ceitec.muni.cz

MORE INFORMATION: http://ls-phd.ceitec.cz/http-ls-phd-ceitec-cz

https://www.ceitec.eu/protein-dna-interactions-konstantinos-tripsianes

Structural Virology

Supervisor: Mgr. Pavel Plevka, Ph.D.

When Staphylococcus aureus cells form a biofilm in the human body they become shielded from the immune system and highly resistant to antibiotics. Current therapeutic options against biofilms are limited to the long-term application of a combination of several antibiotics in high doses or the surgical removal of infected tissues.

Viruses from the Enterovirus genus belong to the family Picornaviridae of human and vertebrate pathogens. Diseases caused by enteroviruses range from upper and lower respiratory tract infections to life-threatening encephalitis. Rhinoviruses are responsible for 40% of the common cold cases that result in yearly cost of tens of billions of US$ in treatments and lost working hours worldwide.

EXAMPLES OF POTENTIAL PHD TOPICS:

  • Structural and time-resolved studies of phage replication in bacterial biofilm
  • Structural study of enterovirus replication in vivo

PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor and phd@ceitec.muni.cz

MORE INFORMATION: http://ls-phd.ceitec.cz/http-ls-phd-ceitec-cz

http://plevkalab.ceitec.cz/jobs/

Structure of Biosystems and Molecular Materials

Supervisor: prof. RNDr. Radek Marek, Ph.D.

The novel forms of nucleotide moieties will be incorporated in silico in oligomers with sequences relevant for biosystems. The biocompatibility of artificial building blocks will be evaluated using advanced methods of quantum chemistry that provide also analytical tools for investigation of crucial noncovalent interactions. Available candidates of modified nucleobases and sugars will be studied experimentally by using NMR spectroscopy in solution.

The project is focused on detailed structural characterization of short purine oligonucleotides clipped by proper sequential motifs that induce parallel orientation of DNA strands. 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 deeper understanding of key noncovalent interactions that contribute to the folding of such systems.

EXAMPLES OF POTENTIAL PHD TOPICS:

  • Designing modified DNA fragments
  • Structure of parallel forms of nucleic acids studied by NMR spectroscopy and molecular modelling

PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact the supervisor and phd@ceitec.muni.cz

MORE INFORMATION: http://ls-phd.ceitec.cz/http-ls-phd-ceitec-cz

https://www.ceitec.eu/structure-of-biosystems-and-molecular-materials-radek-marek

Study field data

Faculty Faculty of Science
Type of study Doctoral
Mode full-time Yes
combined Yes
Standard length of studies 4 years
Language of instruction Czech

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