Introductory lesson

Introductory lesson given by the guarantor of the field of study prof. Lukáš Žídek followed by:

Graphics and color in scientific presentation (presentation given by prof. L. Žídek)

Krepl Miroslav, RNDr., Ph.D.

Dynamic recognition of nucleic acids by proteins and the role of partial disorder
Abstract: Biomolecular dynamics help elucidate complex intramolecular interfaces, such as protein-RNA and protein-DNA complexes, influencing binding affinities, specificities, and formation rates. These interfaces involve dynamic conformational sub-states rather than fixed geometries, enabling dynamic recognition. This mechanism aids highly specific RNA recognition without compromising biological function and is shaped by molecular evolution to optimize binding and kinetics. Dynamic recognition allows rapid, specific RNA interrogation in cells. During my talk, I will present key examples: HuR scanning multiple RNA sequences, Hfq cycling RNAs, RuvC recognizing DNA Holliday junctions, and spontaneous RNA binding to HuR, SRSF1, Hrp48, and TbRGG2 RRMs.I will also mention the methodological challenges associated with computational research of biomolecular complexes.

Mgr. Vladimíra Zlínská

Modulation of FGF receptor activity by DNA aptamers

Dysregulation of fibroblast growth factor signaling is implicated in various diseases, including cancer. Current therapeutics lack specificity, targeting multiple FGFR isoforms and other receptor tyrosine kinases. We identified VZ23, a DNA aptamer with high specificity for FGFR1, effectively inhibiting FGFR1 signaling. By partially resolving the structure of VZ23, we gained fundamental insight into its structural features, enabling the rational design and targeted incorporation of covalent modifications to enhance its stability and biological activity. Our findings highlight DNA aptamers as a promising alternative to current therapeutics for targeting FGFR1-related disorders.

Sofia Blasco Puyuelo - Ph.D. defence

Computational study of nanoparticle induced membrane fusion and peptide selectivity

Drug delivery systems are formulations designed to transport a drug to specific sites in the body while minimizing off-target interactions. Despite the many advances in the development of drug delivery systems over the last decades, certain challenges remain unresolved, such as active cell targeting, or efficient intracellular delivery. In this thesis, we used computational methods to address these challenges. We investigated the design of nanoparticles that induce lipid vesicle fusion for the purpose of intracellular delivery. And we designed peptides that selectively bind bacterial membranes for the purpose of bacterial cell targeting. To design a nanoparticle to induce fusion of lipid vesicles, we explored nanoparticle parameters such as size, prolateness, and ligand interaction strength to identify the optimal parameters that lower the energy barriers of membrane fusion. These findings can aid in the development of antimicrobial peptides with reduced toxicity towards mammalian cells, and in the development of drug delivery systems that target bacteria.

Seminar Cancelled

Seminar Cancelled due to the conference in Nové Hrady

Dirk G. Inzé, Ghent University and Director of the Center for Plant Systems Biology of the VIB

On the occasion of conferring the honorary degree of doctor honoris causa in biological sciences to Dirk G. Inzé, we invite you to a lecture by the laureate entitled "The quest for high-yielding, eco-friendly and climate-resilient crops," which will take place in CEITEC Atrium.

Alexei V. Demchenko, Ph.D. : SLU - Saint Louis University - B11/ROOM 132!!!

Alexei V. Demchenko, Ph.D. - CV and abstract

Přednáška České společnosti chemické
Saint Louis University, USA (hosted by Michaela Wimmerová)

New methods and technologies for the synthesis of glycopharmaceuticals

Complex carbohydrates (glycoconjugates, oligosaccharides, or glycans) are involved in many processes and are referred to as the “essential molecules of life.” Our life begins with fertilization, which takes place via carbohydrate-protein recognition. Our journey with sugars continues with human milk that becomes the ideal first food. Glycans present in human milk called HMO can provide prebiotic effects, function as antimicrobial agents, and supply nutrients for the development of cognition. Throughout our lifetime, sugars are involved in many upkeeping processes and defensive mechanisms including joint lubrication, cell growth, antigenic determination, anti-inflammation, immune response. The explosive growth of glycobiology has increased our understanding of the roles of sugars also as “molecules of death” due to their involvement in pathogenesis of every major disease including cancer, AIDS, pneumonia, septicemia, diabetes, malaria. With improved understanding of functions of glycans, the demand for robust methods to produce both natural glycans and their mimetics has increased. Glycans can be obtained by isolation from natural sources, prepared enzymatically, and/or chemically to study their composition, conformation, interaction with other molecules, and functional roles. Manufacturers are also interested in glycans due to their prebiotic, therapeutic, and diagnostic potential. The discovery of glycans is accelerating aided by advances in separation, analysis, and array technologies. Still, the availability of glycans remains low. The discovery of new methods and accessible technologies that offer new capabilities for obtaining pharmaceutically relevant glycans is at the heart of this presentation.

Prof. Dr. Dina Grohmann- Universität Regensburg

Single-molecule analysis of CRISPR-Cas enzymes

CRISPR-Cas systems constitute the adaptive immune systems of bacteria and archaea. As we scientist only discoverd CRISPR-Cas a few years ago, there is much to be learned about the diversity and function of these complex defence systems. Employing biophysical technqiues like single-molecule FRET, we seek to understand the molecular mechanisms and conformational dynamics of a subset of Cas proteins.

Dr. Bennett Van Houten, University of Pittsburgh

Watching DNA repair at the single molecule level in real-time: seeing is believing

Dr. Bennett Van Houten - CV and abstract

This seminar will present a new rapid and robust method for single molecule analysis of DNA binding proteins from nuclear extracts (SMADNE) of human cells expressing a fluorescently tagged protein of interest (Schaich et al., Nucleic Acids Res. 2023 Apr 24;51(7):e39). SMADNE when combined with the LUMICKS C-trap provides unprecedented observations of DNA repair protein dynamics on damaged DNA. Over the last 18 months our group has been able to analyze the dwell times of 35 proteins or protein variants on DNA substrates using this approach. After a brief introduction to DNA damage and base excision repair, this seminar will discuss new unpublished data, including the DNA binding dynamics of PARP1 and PARP1 variants or DNA LIG3-XRCC1 on nicks in naked DNA and in a nucleosomes. An important glycosylase, TDG, involved in active oxidative demethylation of 5mC through base excision repair will also be discussed (Nat Commun. 2024 Oct 25;15(1):9226.) Finally, the non-specific DNA interactions and the binding behavior to 8-oxoG of purified eGFP-OGG1, purified eGFP-OGG1 added to extracts, and eGFP-OGG1 from human cell nuclear extracts will be directly compared.

Mgr. Monika Čechová, Ph.D. and Mgr. Zuzana Hammerová (Presentations of Ph.D.students)

Mgr. Monika Čechová Ph.D.(Faculty of Informatics, MU)

The bioinformatics in the era of complete T2T human genomes

Mgr. Zuzana Hammerová (PhD student, Faculty of Science, MU)

Glycosyltransferases in M. tuberculosis

Mycobacterium tuberculosis is a pathogenic bacterium with a strong and impermeable saccharide cell wall that protects this bacterium against the human immune system. This cell wall must be synthesized by a variety of glycosyltransferases, however, not all of them have been discovered and characterized. Using a bioinformatics approach, I am discovering novel proteins with potential glycosyltransferase activity that are interesting targets for developing new antituberculosis drugs.

State Holiday

State Holiday

doc. Mgr. Jan Havliš, Dr.

Scientometry or the informal championship in scientific publication

Assoz. Prof. Dr. Dennis Kurzbach - Universität Wien

TBW