CeNT
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Biomolecular Machines Laboratory

Our research interests involve studying the function, dynamics, and physico-chemical properties of nanoscale assemblies to understand their activities in the cell. The main object of our studies is the ribosome – the macromolecular complex responsible for protein synthesis.

The focus of our research is to extend, apply and verify experimentally simulation techniques to study the association of ligands with the ribosomal RNA. The goal is to explore ribosomal internal motions and electrostatic properties, as well as the thermodynamics and kinetics of binding of antibiotics inhibiting the bacterial ribosome.

Research areas include:

  • physicochemical properties of macromolecular complexes
  • design of ligands targeting the bacterial ribosome
  • thermodynamics of interactions between modified oligonucleotides
  • coarse-grained models for proteins and nucleic acids
  • molecular dynamics simulations of RNA systems
  • academic software development for molecular modeling and simulations

We combine theoretical approaches (computational simulations and molecular modeling) with experimental biophysical measurements (absorbance, fluorescence, circular dichroism spectroscopy, isothermal titration calorimetry).

 
Prof. Joanna Trylska
email: joanna@cent.uw.edu.pl
phone: +48 22 55 43683
room: 04.03
Strona laboratorium: http://bionano.cent.uw.edu.pl/People/JoannaTrylska

Areas of specialization:

  • modeling macromolecular nanoassemblies such as the ribosome
  • development of coarse-grained models for proteins and nucleic acids
  • antibacterial antisense oligonucleotides
  • thermodynamics and energetics of ribosome and its complexes with antibiotics
  • enzymatic activity of proteases
  • quantum-classical molecular dynamics methods to simulate proton transfer processes in enzymatic reactions

Employment:

  • January 2012 – present Associate Professor, Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097 Warsaw, Poland
  • May 2009 – December 2011 Associate Professor, Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw, Pawińskiego 5A, 02-106 Warsaw, Poland
  • Feb 2005 – May 2009 Assistant Professor, Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw, Pawińskiego 5A, 02-106 Warsaw, Poland
  • Jan 2003 – Jan 2005 Post-doctoral Researcher, University of California at San Diego, Department of Chemistry and Biochemistry and Center for Theoretical Biological Physics, 9500 Gilman Drive, La Jolla, CA 92093-0365, USA
  • Dec 2001 – Dec 2002 Faculty Adjunct, Interdisciplinary Centre for Mathematical and Computational Modelling (ICM), University of Warsaw, Pawińskiego 5A, 02-106 Warsaw, Poland
  • Sept 2000 – Nov 2001 Research Assistant, University of Warsaw, Poland

Education:

  • Sept 2017 – Professor title awarded by the President of Poland
  • May 2009 – habilitation colloquium, Faculty of Physics, University of Warsaw, thesis: “Internal dynamics, association and energetics of binding of ligands with the ribosome”
  • Oct 2001 – PhD degree at Faculty of Physics, University of Warsaw, specialization: molecular biophysics, thesis “Computational Modelling of Protonation Equilibria and Reaction Mechanism of HIV-1 Protease”
  • 1995 – 2000 PhD student, University of Warsaw, Faculty of Physics, Department of Biophysics
  • 1989 – 1995 student, University of Warsaw, Faculty of Physics, specialization: molecular biophysics, MSc degree in physics, thesis entitled “Molecular modelling studies of physicochemical properties of human erythrocytic purine nucleoside phosphorylase”

Fellowships and Awards:

  • 2017 – “Biophysicist in Profile” an article in Biophysical Society Newsletter
  • 2016 – a silver medal from the Rector for the 200 anniversary of the University of Warsaw
  • since 2011 – Associate Editor of BMC Biophysics
  • 2015, 2012, 2010, 2009 – University of Warsaw Rector’s award for research achievements
  • 2014 – nomination by the Foundation for Polish Science and Robert Bosh Foundation to AcademiaNet initiative
  • 2008 – University of Warsaw Rector fellowship
  • 2007 – 2012 – Foundation for Polish Science “Focus” fellowship
  • 2003 – 2004 – NSF Center for Theoretical Biological Physics fellowship
  • 1995 – 2000 – Faculty of Physics, PhD fellowship
  • 1993 – 1995 – Faculty of Physics, student’s fellowship

Memberships:

  • The International Society of Quantum Biology and Pharmacology
  • Biophysical Society
  • American Chemical Society
  • Polish Bioinformatics Society

Teaching experience:

  • lecture on “Modelling Macromoleculat Machines”, courses “Introduction to Physics”, “Molecular Quantum Mechanics”, “Biophysics”
  • laboratories in physics, molecular modelling methods

Title Project Leader Project period Project funding
Development of new antibacterial agents based on lytic enzymes produced by bacteriophages Monika Wojciechowska 2024 - 2029 NCN, SONATA BIS 13
Biological membranes and macromolecular crowding in the function of the hepatitis C virus proteases Joanna Trylska 2023 - 2027 PRELUDIUM BIS 4, NCN
Making use of siderophore transport systems to deliver peptide nucleic acids to bacterial cells Joanna Trylska 2021 - 2026 OPUS 19, NCN
Conjugates of peptide nucleic acids with aminoglycosides and fluoroquinolones as a novel strategy to target multi-drug resistant bacteria Izabela Siekierska 2024 - 2026 PRELUDIUM 22, NCN
Conjugates of aminoglycosides with amphipathic peptides as antibacterials Monika Wojciechowska 2020 - 2024 SONATA 15, NCN
Ribozyme-based potential antibacterial strategy Joanna Miszkiewicz 2021 - 2023 PRELUDIUM 19, NCN
Opracowanie efektywnych związków przeciwbakteryjnych poprzez stabilizację struktury peptydów penetrujących błony biologiczne Joanna Trylska 2022 - 2023 IDUB New Ideas
Why and how does cellular crowding affect enzymatic activity? Joanna Trylska 2022 - 2023 IDUB Tandems for Excellence
The effect of crowded environment on the catalytic activity and dynamics of viral proteases Joanna Trylska 2017 - 2021 OPUS 12, NCN
Przewidywanie powinowactwa ligandów do RNA na przykładzie ryboprzełącznika aminoglikozydowego. Joanna Trylska 2018 - 2021 HARMONIA 9, NCN
In quest for the mechanism of transport of vitamin B12-peptide nucleic acid conjugates to E. coli cells Tomasz Pieńko 2018 - 2021 PRELUDIUM 14, NCN
Vitamin B12 as a delivery vehicle for antibacterial oligonucleotide analogues Joanna Trylska 2014 - 2019 SYMFONIA, NCN
Przewidywanie powinowactwa ligandów do RNA na przykładzie ryboprzełącznika aminoglikozydowego. Joanna Trylska - HARMONIA, NCN
Molecular dynamics in multidimensional space explains how mutations affect the association path of neomycin to a riboswitch
Chyży P., Kulik M., Shinobu A., Re S., Sugita Y., Trylska J.
Proceedings of the National Academy of Sciences of the United States of America, 121 (15), art. no. e2317197121
Editorial: Combining Simulations, Theory, and Experiments into Multiscale Models of Biological Events
Fabio Trovato, Joanna Trylska, Peter J. Bond, Peter G. Wolynes
Front. Mol. Biosciences, vol. 8, 797754
Stapled anoplin as an antibacterial agent
Monika Wojciechowska, Julia Macyszyn, Joanna Miszkiewicz, Renata Grzela, Joanna Trylska
Frontiers in Microbiology, vol. 12, 772038
Insight into the binding and hydrolytic preferences of hNudt16 based on nucleotide diphosphate substrates
Magdalena Chrabąszczewska, Maria Winiewska-Szajewska, Natalia Ostrowska, Elżbieta Bojarska, Janusz Stępiński, Łukasz Mancewicz, Maciej Łukaszewicz, Joanna Trylska, Michał Taube, Maciej Kozak, Edward Darżynkiewicz, Renata Grzela
Int. J. Mol. Sci. 22(20), 10929
Crowding affects structural dynamics and contributes to membrane association of the NS3/4A complex
Natalia Ostrowska, Michael Feig, JoannaTrylska
Biophys. J., 20:3795–3806
Vitamin B12 – Peptide Nucleic Acid Conjugates
Monika Wojciechowska, Joanna Trylska
Methods in Molecular Biology, Springer, vol. 2355, p. 65-82
Vitamin B12-peptide nucleic acids use the BtuB receptor to pass through the E. coli outer membrane
Tomasz Pieńko, Jakub Czarnecki, Marcin Równicki, Monika Wojciechowska, Aleksandra J Wierzba, Dorota Gryko, Dariusz Bartosik, Joanna Trylska
Biophys. J., vol. 120, p. 725–737
Mutations of N1 riboswitch affect its dynamics and recognition by neomycin through conformational selection
Piotr Chyży, Marta Kulik, Suyong Re, Yuji Sugita, Joanna Trylska
Front. Mol. Biosciences, vol. 8, 633130
Kinetic analysis of IFIT1 and IFIT5 interactions with different native and engineered RNAs and its consequences for designing mRNA-based therapeutics
Miedziak, B., Dobieżyńska, A., Darżynkiewicz, Z. M., Bartkowska, J., Miszkiewicz, J., Kowalska, J., ... & Darzynkiewicz, E.
RNA, 26(1), 58-68.
Development of bis-ANS-based modified fluorescence titration assay for IFIT/RNA studies
Dobieżyńska, A., Miszkiewicz, J., Darżynkiewicz, Z. M., Tyras, M., Stankiewicz-Drogoń, A., Trylska, J., ... & Grzela, R.
Biochemical and Biophysical Research Communications, 533(3), 391-396
Conformational changes of anoplin, W-MreB1-9 and (KFF)3K peptides in proximity to membrane environments
Wojciechowska, M., Miszkiewicz, J., & Trylska, J.
International journal of molecular sciences, 21(24), 9672
Targeting type II toxin-antitoxin systems as antibacterial strategies
Równicki, M., Lasek, R., Trylska, J., & Bartosik, D.
Toxins, 12(9), 568
The effect of the crowded environment on the activity and inhibition of the NS3/4A protease
Popielec, A., Ostrowska, N., Wojciechowska, M., Feig, M., & Trylska, J.
Biochimie, 176, 169-180
Extracellular loops of BtuB facilitate transport of vitamin B12 through the outer membrane of E. coli
Pieńko, T., & Trylska, J.
PLOS Computational Biology, 16(7), e1008024
Antibacterial peptide nucleic acids – facts and perspectives
Wojciechowska, M., Równicki, M., Mieczkowski, A., Miszkiewicz, J., & Trylska, J.
Molecules, 25(3), 559
Inhibition of Escherichia coli Growth by Vitamin B 12 –Peptide Nucleic Acid Conjugates
Rownicki, M., Dabrowska, Z., Wojciechowska, M., Wierzba, A. J., Maximova, K., Gryko, D., Trylska, J. (2019).
ACS Omega, 4(1), 819-824
Enzyme kinetics in crowded solutions from isothermal titration calorimetry
Maximova, K., Wojtczak, J., & Trylska, J. (2019).
Analytical Biochemistry, 567, 96-105
Thermodynamics of the fourU RNA thermal switch derived from molecular dynamics simulations and spectroscopic techniques
Leonarski, F., Jasiński, M., & Trylska, J. (2019).
Biochimie, 156, 22-32
Vitamin B12 transports modified RNA into E. coli and S. Typhimurium cells
Giedyk, M., Jackowska, A., Równicki, M., Kolanowska, M., Trylska, J., & Gryko, D.
Chem Communications, 55(6), 763-766.
Computational methods used to explore transport events in biological systems
Pieńko, T., & Trylska, J.
Journal of Chemical Information and Modeling, 59(5), 1772-1781.
Thermal stability of peptide nucleic acid complexes
Maciej Jasiński, Joanna Miszkiewicz, Michael Feig and Joanna Trylska
J. Phys. Chem. B
Modeling crowded environment in molecular simulations
Natalia Ostrowska, Michael Feig and Joanna Trylska
Frontiers in Molecular Biosciences
Enzymatic activity of human immunodeficiency virus type 1 protease in dilute and crowded solutions
Ksenia Maximova, Jakub Wojtczak, Joanna Trylska
European Biophysics Journal
Peptidomimetic inhibitors targeting the membrane-binding site of the neutrophil proteinase
Ksenia Maximova, Nathalie Reuter, Joanna Trylska
Biochimica et Biophysica Acta (BBA). Biomembranes
Towards catalytic antibiotics: redesign of aminoglycosides to catalytically disable bacterial ribosomes
Smolkin, B., Khononov, A., Pieńko, T., Shavit, M., Belakhov, V., Trylska, J., & Baasov, T.
ChemBioChem, 20(2), 247-259
Exploring Eukaryotic Versus Prokaryotic Ribosomal RNA Recognition with Aminoglycoside Derivatives
Sabbavarapu, N. M., Pieńko, T., Zalman, B. H., Trylska, J., & Baasov, T. (2018).
MedChemComm, 9(3), 503-508.
d-Peptides as inhibitors of PR3-membrane interactions
Maximova, K., Venken, T., Reuter, N. and Trylska, J., (2018).
Biochimica et Biophysica Acta (BBA)-Biomembranes, 1860(2), pp.458-466.
Interactions of 2′-O-methyl oligoribonucleotides with the RNA models of the 30S subunit A-site
Jasiński, M., Kulik, M., Wojciechowska, M., Stolarski, R., & Trylska, J. (2018).
PloS one, 13(1), e0191138
Molecular dynamics simulations suggest why the A2058G mutation in 23S RNA results in bacterial resistance against clindamycin
Kulczycka-Mierzejewska, K., Sadlej, J., & Trylska, J. (2018).
Journal of molecular modeling, 24(8), 191
Improved Force Fields for Peptide Nucleic Acids with Optimized Backbone Torsion Parameters
Jasiński, M., Feig, M., & Trylska, J. (2018).
Journal of chemical theory and computation
Thermodynamics of the pseudo‐knot in helix 18 of 16S ribosomal RNA
Wojciechowska, M., Dudek, M., & Trylska, J. (2018).
Biopolymers, 109(4), e23116
Exploring Eukaryotic Versus Prokaryotic Ribosomal RNA Recognition with Aminoglycoside Derivatives
Sabbavarapu, N. M., Pieńko, T., Zalman, B. H., Trylska, J., & Baasov, T. (2018).
MedChemComm, 9(3), 503-508.
Molecular mechanisms for dynamic regulation of N1 riboswitch by aminoglycosides
Kulik, M., Takaharu, M., Sugita, Y., Trylska, J. (2018)
Nucleic Acids Research
Artificial Activation of Escherichia coli mazEF and hipBA Toxin–Antitoxin Systems by Antisense Peptide Nucleic Acids as an Antibacterial Strategy
Równicki, M., Pieńko, T., Czarnecki, J., Kolanowska, M., Bartosik, D., & Trylska, J.
Frontiers in Microbiology, 9
Antimicrobial synergy between mRNA targeted peptide nucleic acid and antibiotics in E. coli
Castillo, J. I., Równicki, M., Wojciechowska, M., & Trylska, J.
Bioorganic & Medicinal Chemistry Letters, 28(18)
Does a Conjugation Site Affect Transport of Vitamin B12–Peptide Nucleic Acid Conjugates into Bacterial Cells?
Wierzba, A. J., Maximova, K., Wincenciuk, A., Równicki, M., Wojciechowska, M., Nexø, E., . . . & Gryko, D.
Chemistry – A European Journal, 24(70)
Vitamin B12 transports modified RNA into E. coli and S. Typhimurium cells
Giedyk, M., Jackowska, A., Równicki, M., Kolanowska, M., Trylska, J., & Gryko, D.
Chemical Communications, 55(6), 763-766.
Analysis of ribosomal inter-subunit sites as targets for complementary oligonucleotides
S.G. Thoduka, P.A. Zaleski, Z. Dąbrowska, M. Równicki, J. Stróżecka, A. Górska, M. Olejniczak, J. Trylska
Biopolymers, 2017, 107(4), e23004
Analysis of ribosomal inter‐subunit sites as targets for complementary oligonucleotides.
Thoduka, S. G., Zaleski, P. A., Dąbrowska, Z., Równicki, M., Stróżecka, J., Górska, A., ... & Trylska, J. (2017).
Biopolymers, 107(4).
Helix 69 of Escherichia coli 23S ribosomal RNA as a peptide nucleic acid target.
Kulik, M., Markowska-Zagrajek, A., Wojciechowska, M., Grzela, R., Wituła, T., & Trylska, J. (2017).
Biochimie, 138, 32-42.
Molecular dynamics simulations of l-RNA involving homo-and heterochiral complexes.
Dudek, M., & Trylska, J. (2017).
Journal of chemical theory and computation, 13(3), 1244-1253.
Vitamin B12 as a carrier of peptide nucleic acid (PNA) into bacterial cells
Równicki, M., Wojciechowska, M., Wierzba, A. J., Czarnecki, J., Bartosik, D., Gryko, D., & Trylska, J. (2017).
Scientific reports, 7(1), 7644.
Conformational Dynamics of Cyanocobalamin and Its Conjugates with Peptide Nucleic Acids
Pieńko, T., Wierzba, A. J., Wojciechowska, M., Gryko, D., & Trylska, J.
The Journal of Physical Chemistry B, 121(14)
Vitamin B12 suitably tailored for disulfide-based conjugation
Wierzba, A., Wojciechowska, M., Trylska, J., & Gryko, D. (2016).
Bioconjugate chemistry, 27(1), 189-197
Scanning of 16S ribosomal RNA for peptide nucleic acid targets.
Górska, A., Markowska-Zagrajek, A., Równicki, M., & Trylska, J. (2016).
The Journal of Physical Chemistry B, 120(33), 8369-8378.
Conformational space of clindamycin studied by quantum and full-atom molecular dynamics-Supplementary Material.
Kulczycka-Mierzejewska, K., Trylska, J., & Sadlej, J.
Journal of Molecular Modeling,22:20
Conformational space of clindamycin studied by ab inito and full-atom molecular dynamics.
Kulczycka-Mierzejewska, K., Trylska, J., & Sadlej, J. (2016).
Journal of molecular modeling, 22(1), 20.
Effects of Spatially-Dependent Mobilities on the Kinetics of the Diffusion-Controlled Association Derived from the First Passage Time Approach
Długosz, M., & Antosiewicz, J. M. (2016).
The Journal of Physical Chemistry B, 120(29), 7114-7127.
MINT: software to identify motifs and short-range interactions in trajectories of nucleic acids
Górska, A., Jasiński, M., & Trylska, J. (2015)
Nucleic acids research, 43(17), e114-e114
Kinetics of trypsin catalyzed hydrolysis determined by isothermal titration calorymetry
Maximova, K., & Trylska, J. (2015)
Analytical biochemistry, 486, 24-34
RedMDStream: Parametrization and simulation toolbox for coarse-grained molecular dynamics models
Leonarski, F., & Trylska, J. (2015)
Biophysical journal, 108(8), 1843-1847
Conformational dynamics of bacterial and human cytoplasmic models of the ribosomal A-site
Panecka, J., Šponer, J., & Trylska, J. (2015)
Biochimie, 112, 96-110.
Electrostatic interactions in aminoglycoside-RNA complexes.
Kulik, M., Goral, A. M., Jasiński, M., Dominiak, P. M., & Trylska, J. (2015).
Biophysical journal, 108(3), 655-665.
Interplay of the bacterial ribosomal A-site, S12 protein mutations and paromomycin binding: a molecular dynamics study.
Panecka, J., Mura, C., & Trylska, J. (2014).
PloS one, 9(11), e111811.
Inhibition of bacterial translation and growth by antisense peptide nucleic acids and their potential application in biotechnology
Markowska-Zagrajek, A., Rownicki, M., & Trylska, J. (2014)
POSTEPY MIKROBIOLOGII, 53(3), 255-263
Interactions of amikacin with the RNA model of the ribosomal A-site: computational, spectroscopic and calorimetric studies.
Dudek, M., Romanowska, J., Wituła, T., & Trylska, J. (2014).
Biochimie, 102, 188-202.
Role of S-turn2 in the structure, dynamics, and function of mitochondrial ribosomal A-site. A bioinformatics and molecular dynamics simulation study.
Panecka, J., Havrila, M., Réblová, K., Šponer, J., & Trylska, J. (2014).
The Journal of Physical Chemistry B, 118(24), 6687-6701.
Modeling nucleic acids at the residue-level resolution.
Leonarski, F., & Trylska, J. (2014).
Computational Methods to Study the Structure and Dynamics of Biomolecules and Biomolecular Processes (pp. 109-149). Springer, Berlin, Heidelberg
Evolutionary algorithm in the optimization of a coarse-grained force field.
Leonarski, F., Trovato, F., Tozzini, V., Les, A., & Trylska, J. (2013).
Journal of chemical theory and computation, 9(11), 4874-4889.
Using Sequence-Specific Oligonucleotides To Inhibit Bacterial rRNA
Trylska, J., Thoduka, S. G., & Dąbrowska, Z. (2013).
ACS Chemical Biology, 8(6), 1101-1109.
Comparing aminoglycoside binding s ites in bacterial ribosomal RNA and aminoglycoside modifying enzymes
Romanowska, J., Reuter, N., & Trylska, J. (2013)
Proteins: Structure, Function, and Bioinformatics, 81(1), 63-80
Determining geometrically stable domains in molecular conformation sets.
Romanowska, J., Nowinski, K. S., & Trylska, J. (2012).
Journal of chemical theory and computation, 8(8), 2588-2599.
Molecular dynamics techniques in the studies of the bacterial ribosome.
Panecka, J., & Trylska, J.( 2012, June).
AIP Conference Proceedings (Vol. 1456, No. 1, pp. 207-214).
Contributions of far-field hydrodynamic interactions to the kinetics of electrostatically driven molecular association
Długosz, M., Antosiewicz, J. M., Zieliński, P., & Trylska, J. (2012)
The Journal of Physical Chemistry B, 116(18), 5437-5447.
Unwrapping of nucleosomal DNA ends: a multiscale molecular dynamics study
Voltz, K., Trylska, J., Calimet, N., Smith, J. C., & Langowski, J. (2012)
Biophysical journal, 102(4), 849-858
Quantum mechanical studies of lincosamides
Kulczycka-Mierzejewska, K., Trylska, J., & Sadlej, J. (2012)
Journal of molecular modeling, 18(6), 2727-2740
Constributions of Far-Field Hydrodynamic Interactions to the Kinetics of Electrostatically-Driven Molecular Association
Długosz, M., Antosiewicz, J. M., Zieliński, P., & Trylska, J. (2012)
Journal of Physical Chemistry B, 116(18), 5437-5447