Introductory lesson

TBW

Eva Nagyová and Monika Kuchlei Sieberová: Starter pack for researchers’ (in)visibility

Rectorate, MU

Abstract:

Discover how scientists can communicate effectively with diverse audiences, boost their visibility, and make an impact beyond traditional metrics. This talk covers expert science communication, practical tools like persistent identifiers and professional profiles, social networks including ResearchGate, X, and LinkedIn, and essential skills for popularizing science to the public.

Marko Anderluh: New small molecular inhibitors form unexpected interactions with their targets: case studies of DNA Gyrase/topoIV and Galectin-8 inhibitors

University of Ljublana, Slovenia (host of M. Wimmerová)

Abstract:

The talk addresses our quest in the design of DNA Gyrase/topoIV inhibitors and galectin-8 inhibitors over the 10-year span of research work. The talk will be divided into 2 parts.

In the first part of the talk, I will focus on our quest in design of DNA gyrase inhibitors. We have focused on Novel bacterial type II topoisomerase inhibitors (NBTIs) that stabilize single-strand DNA cleavage breaks by DNA gyrase. Although the class is known for almost two decades, their exact mechanism of action has remained hypothetical until now. To address this issue, we have designed a small library of NBTIs with an improved DNA gyrase-binding moiety resulting in low nanomolar inhibition and very potent antibacterial activity. They stabilize single-stranded cleavage complexes and, importantly, we have obtained the crystal structure where an NBTI binds gyrase–DNA in a single conformation lacking apparent static disorder. This directly proves the previously postulated NBTI mechanism of action and shows that they stabilize single-strand cleavage through asymmetric intercalation with a shift of the scissile phosphate. The crystal structure shows that the chlorine forms a halogen bond with the backbone carbonyls of the two symmetry-related Ala68 residues. To the best of our knowledge, such a so-called symmetrical bifurcated halogen bond has not been identified in a biological system until now. From this more chemico-biological part of the research, we have moved to more medicinal chemistry-related work in which we optimized the NBTI potency and diminished hERG inhibition. At last, we performed in vivo studies (mouse thigh infection model), which show efficacy of our compounds in in vivo setting.

In the second part of the talk, I will present our results in designing potent and selective galectin-8 inhibitors. We have made a series of 3-substituted D-galactal derivatives, 3-lactoylgalactosides and 3-triazolyl-1-thiogalactosides as galectin-8 inhibitors and show the influence of various substitutions on D-galactose and D-galactal core on the galectin-8 affinity and selectivity. The synthetic data will be corroborated by structural data that allowed us drug design fine-tuning. Finally, I will present a new optimized focused D-galactosides library that reached nanomolar Kd on galectin-8 for the first time. In particular, I will present recently published data on how we obtained such affinity by new D-galactosides that form non-canonical cation-p interactions with Gal-8N. will also present some data on how galectin-8 may be used in Pseudomonas aeruginosa keratitis and other diseases.

Martina Mašková: Popularization of science on the radio

Český rozhlas, CR

Abstract:

Martina Mašková hosts the Laboratoř (Laboratory) program on Český rozhlas Plus and also presents the morning broadcast. Previously, she prepared the Téma dne (Topic of the Day) and Souvislosti (Connections) programs. She has been working in radio since 1996, after studying biology and chemistry in Prague and completing a one-year media course in Angers, France. She started at ČRo 6 – Radio Free Europe, worked for seven years at the BBC in Prague and London, and then returned to Czech Radio. She occasionally records radio documentaries, including in Germany, Switzerland, Ukraine, Namibia, the Palestinian territories, and Israel.

In addition to her main profession as a presenter, she has experience from a number of reporting trips, internships at British, French, and German radio stations, and study stays at European institutions and in the US. Since the beginning of her professional career, she has been involved in popularizing science, and in recent years she has deepened her interest in social media. Her presentation will be an interesting overview of how to popularize scienceand how to work with social media in our favour.

Session cancelled

Session cancelled due to conference in Nové Hrady 19.3.- 23.3.2026

David Bednář: FireProt: Advancing Protein Stability Engineering through Integrated Computational Approaches

Masaryk University, Brno, CZ

Abstract:

Protein stability is a key factor in understanding function, designing therapeutics, and engineering enzymes for biotechnological applications. The FireProt approach combines computational predictions with experimental validation to optimize protein stability efficiently. Using integrated computational methods, including energy calculations and evolutionary analysis, FireProt identifies stabilizing mutations while minimizing negative effects on protein function. This strategy enables the rational design of robust proteins for industrial, medical, and research purposes. The approach has been applied to a variety of enzymes, demonstrating significant improvements in thermal and chemical stability. By combining structural modeling with high-throughput mutational analysis, the workflow accelerates protein engineering while reducing experimental costs. The method also considers protein dynamics and folding pathways to ensure mutations support natural conformational flexibility. FireProt provides a framework for predicting synergistic effects of multiple mutations, leading to highly stable variants. Its computational efficiency allows rapid screening of candidate mutations before laboratory testing. Overall, FireProt exemplifies how computational tools can transform protein engineering and facilitate the design of proteins with enhanced stability and function.

Catherine H. Freudenreich: Replication and repair of structure-forming repeats: role of repositioning to the nuclear periphery

Tufts University, USA

Abstract:

All cells encounter replication barriers upon genome duplication and must overcome those barriers to survive. Many repeat sequences can form alternative DNA structures that interfere with replication and repair. This can lead to disease-causing repeat expansions. Alternatively, breaks within structure-forming repeats cause chromosome deletions and rearrangements, which are common in cancer cells undergoing replication stress. One strategy that cells use to overcome some types of replication barriers or difficult-to-repair lesions is repositioning to the nuclear periphery. I will describe research from my lab on how structure-forming DNA repeats are replicated and repaired and the role of relocation to the nuclear pore in these processes. Recent results on the mechanisms used to move damaged chromosomes to the nuclear pore and the role of this pathway in protecting genome instability will be covered.

Marek Šebesta: On the crosstalk between transcription and DNA repair

NCBR, MUNI, BRNO, CZ

Abstract:

Transcription is central to how cells use and protect their DNA. It operates alongside replication, DNA repair, and recombination; processes that all depend on the same DNA template and therefore must be tightly coordinated. When RNA polymerase II (RNAPII), the enzyme, which carries out transcription, pauses for too long or at the wrong place, it can obstruct other DNA-based processes and increase the risk of genome instability. Yet transcription also helps cells repair deleterious lesions such as DNA double-stranded breaks. Using examples from our recent work, I will discuss how we may reconcile these seemingly opposing roles of transcription, with a particular focus on our unpublished findings.

Anne Imberty: Lectins and lectoms for deciphering the glycocode

National Centre for Scientific Research, France (host of M. Wimmerová)

Abstract:

A large number of pathogenic microorganisms display receptors for specific recognition and adhesion to the glycoconjugates present on human tissues.  In addition to membrane-bound adhesins, soluble lectins are involved in lung infections caused by the bacteria Pseudomonas aeruginosa and Burkholderia cepacia and by the fungus Aspergillus fumigatus that are responsible for hospital-acquired diseases. The multivalency of lectin is proposed to play a role in their strong avidity for glycosylated cell surfaces, in their specific binding to targeted human tissues, and also in their ability to affect membrane dynamics by clustering glycosphingolipids, resulting in some cases in internalization of intracellular pathogens.

Accumulated knowledge about the structures of the lectins and the interactions with host glycoconjugates has led to the design of powerful glyco-derived inhibitors that can serve as antimicrobial therapeutic agents, as a complement to or an alternative to antibiotic therapy. Several strategies are developed with development of glycoderivatives and/or multivalent glycostructures. The structural role of calcium present in the binding site of fucose and galactose specific lectins has been investigated through x-ray and neutron crystallography [1] and novel inhibition strategy with using carbohydrate glycomimetics and non-carbohydrate glycomimetics are being developped [2,3].

Structural information on lectins is now organized in databases with possibility for datamining of lectin sequences in genomes [4].  This opens the possibility to develop tools from bacterial lectins, that can be used for purification and labelling glycoconjugates, vectorisation or as glue for creating artificial tissue. Synthetic glycobiology offers innovative methods for building super-lectins as novel architectures [5].

References:

1. L. Gajdos, M.P. Blakeley, M. Haertlein, V.T. Forsyth, J.M. Devos, A. Imberty, Nature Com. 2022,13,194.
   2. E. Zahorska, L.M. Denig, S. Lienenklaus, S. Kuhaudomlarp, T. Tschernig, P. Lipp, A. Munder, E. Gillon, S. Minervini, V. Verkhova, A. Imberty, S. Wagner, A. Titz, JACS Au 2024, 4, 4715–4728.
2. S. Leusmann, E. Siebs, A. Varrot, S.Kuhaudomlarp, A. Imberty, B. Kuhn, C. Lerner, U. Grether & A. Titz, Angew. Chem. 2025, 64, e202508864.
   4. F. Bonnardel, J. Mariethoz, S. Perez, A. Imberty, F. Lisacek, Nucleic Acids Res. 2021, 49, D1548-D1554.
   5. S. Notova, A. Imberty, Curr. Opin. Chem. Biol. 2023, 73, 102275.

Matthias Thoms: Structural Basis of Eukaryotic Ribosome Assembly

Ludwig-Maximilians, Universität München, Germany

Abstract: 

Ribosomes are universal molecular machines that synthesize proteins in all living organisms. Composed of ribosomal RNA (rRNA) and ribosomal proteins, ribosomes assemble into two subunits: the small (40S) subunit, which decodes messenger RNA (mRNA), and the large (60S) subunit, which catalyzes peptide bond formation. The assembly of eukaryotic ribosomes is a highly dynamic and energy-consuming process that requires more than 200 assembly factors to guide rRNA processing, modification and folding, as well as ribosomal protein incorporation.
Advances in cryo-electron microscopy (cryo-EM) have enabled visualization of ribosome assembly intermediates, providing unprecedented insight into this complex process. Here, I will present our work on key structural transitions during eukaryotic ribosome biogenesis, focusing on the role of RNA helicases and small nucleolar ribonucleoprotein particles (snoRNPs) in promoting the assembly of the two ribosomal subunits.
Together, these findings illustrate how coordinated structural rearrangements drive the assembly of the ribosome.

Jozef Hritz

NCBR, MUNI, BRNO, CZ

TBW

Gabriel Demo

CEITEC, MUNI, BRNO, CZ

Abstract:

Ribosomes are essential molecular machines that produce proteins in every living cell, and their proper assembly and activation are critical for life. In this talk, two complementary studies will be presented that reveal how cells carefully control this process to ensure accurate and efficient protein synthesis. First, it will be shown how defects in ribosome assembly - specifically the absence of a key bacterial biogenesis factor called RimM - trigger a quality control mechanism that delays ribosome activation. Second, using ensemble cryo-electron microscopy, it will be shown how bacterial initiation factors guide the formation of functional ribosomes by controlling subunit joining and driving dynamic structural changes. Together, these findings highlight how ribosome assembly and activation are coordinated to maintain the fidelity of protein synthesis.

Kostas Tripsianes: Studying biomolecular structures, interactions, and molecular mechanisms using advanced NMR techniques

Abtsract:
 
As a structural tool, Nuclear Magnetic Resonance (NMR) is highly complementary to X-ray crystallography and cryo-electron microscopy. Here I discuss NMR applications to protein structures, interactions, and molecular mechanisms that shaped my scientific career over the last twenty years and highlight my future NMR-based research plans

Session cancelled

Session cancelled due to Dies Academicus and a conference in Valtice