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Department of Biophysics

Head: Professor Wojciech Bal

There are six research groups in the Department:

  1. Prof. Wojciech Bal studies mechanisms of action of biologically active metal ions.
  2. Prof. Michał Dadlez investigates mechanisms of oligomerisation of Alzheimer disease Aβ peptides and their interactions with receptors.
  3. Assoc. Prof. Andrzej Dziembowski conducts research on RNA metabolism in yeast and on large protein complexes.
  4. Assoc. Prof. Jarosław Poznański follows various aspects of relationships between macromolecular structure and biological activity.
  5. Dr. Bożenna Rempoła is engaged in investigations aimed explaining functions of individual proteins of Saccharomyces cerevisiae yeast.
  6. Dr. Aleksandra Wysłouch-Cieszyńska studies proteomic, structural and functional aspects of posttranslational protein modifications, with special attention to S-nitrosylation in mammalian cells.

The research in the Department benefits from intense networking between leaders and members of its groups. One recent example is provided by a successful joint application for an Innovative Economy applied research grant between Bal, Dadlez and Wysłouch-Cieszyńska groups (Electrochemical biosensors for detection of activation of RAGE receptors – tools of cheap teranostics, WND-POIG.01.01.02-00-048/09)

 


 Functional analysis of open reading frames of Saccharomyces cerevisiae

Group leader: Dr. Bożenna Rempoła
Staff: M.Sc. Iga Zając (Ph.D. student)

Two subjects are being studied: one in collaboration with the Department of Genetics (the group of Prof. Joanna Rytka) and the second in collaboration with Dr. Anna Szkopińska, head of Research Project “Regulation of the biosynthesis of mevalonate-pathway derivatives in yeast Saccharomyces cerevisiae.”

  1. Our investigations concern the role of the Saccharomyces cerevisiae genes CCZ1 and YPT7 in sporulation, a process equivalent to gametogenesis in higher Eucaryota. It includes meiotic DNA synthesis, recombination, two meiotic divisions and spores formation. Ccz1p and Ypt7p interact physically and are involved in intracellular transport. They are essential for autophagy and sporulation processes. Our results indicate that the sporulation program is initiated in the absence of both proteins, Ccz1p and Ypt7p, however they are required for essential but different steps in the early stages of meiosis I.
  2. The yeast RER2 gene encoding one of two yeast cis-prenyltransferase is involved in dolichol synthesis and is important for N and O protein glycosylation and for the formation GPI anchors. Using TAP tagging method, Nus1p (nuclear undecaprenyl pyrophosphate synthase, putative prenyltransferase) was identified as a protein potentially interacting with cis-prenyltransferase, Rer2p. Verification of this finding and investigation on the biological role of Nus1p are in progress.

 


 The studies of early steps of protein aggregation and folding

Group leader: Prof. Michał Dadlez
Staff:

Current projects:

Research grants:

Selected publications:

 

 


Structural and functional consequences of protein post-translational modifications

Group leader: Dr. Aleksandra Wysłouch-Cieszyńska

Staff: M.Sc. Monika Zaręba, Lilia Zhukova, students: Ilona Zielińska, Magdalena Sulima 

Major research directions:

(a) structural and functional consequences of S-nitrosylation of calcium binding S100 proteins. (b) interaction of selectively S-nitrosylated S100A1 and S100B proteins with metal ions and target proteins such as the extracellular receptor RAGE and p53 protein; (c) development and optimization of strategies for mass spectrometry-based proteomic analysis of endogenous protein S-nitrosylation; (d) proteomic studies of changes in the cellular “S-nitrosome” in several experimental models in which an imbalance in the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) is observed. 

 

Research grants:

2010-2013 "Electrochemical biosensors for detection of activation of RAGE receptors – tools of cheap teranostics"
                (Structural Funds, POIG Ministry of Sciences and Higher Education)
2007-2010 "Protein S-nitrosylation and Cdk5 dependent phosphorylation – proteomic studies of synaptosomes from
                 transgenic mice - models of Alzheimer disease" (Ministry of Sciences and Higher Education)
2003-2007 "Redox modification of proteins: interaction of S100B protein with its extracellular receptor RAGE"
                 (Ministry of Sciences and Higher Education)

 

Selected publications:

  1. A. Krężel, E. Kopera, A. M. Protas, J. Poznański, A. Wysłouch-Cieszyńska, W. Bal, Sequence-specific Ni(II)-dependent Peptide Bond Hydrolysis for Protein Engineering. Combinatorial Library Determination of Optimal Sequences. J. Am. Chem. Soc. (2010), 132, 3355-3366.
  2. van Dieck J., Teufel D.P., Jaulent A.M., Fernandez-Fernandez M.R., Rutherford T.J., Wysłouch-Cieszyńska A., Fersht A.R., Posttranslational Modifications Affect the Interaction of S100 Proteins with Tumor Suppressor p53. J Mol Biol. (2009), 394, 922-30
  3. Smirnova J., Zhukova L., Witkiewicz-Kucharczyk A., Kopera E., Olędzki J., Wysłouch-Cieszyńska A., Palumaa P., Hartwig A., Bal W. Reaction of the XPA zinc finger with GSNO. Chem. Res. Toxicol. (2008) 21: 386-392
  4. Szurmak B., Wysłouch-Cieszyńska A., Wszelaka-Rylik M., Bal W., Dobrzanska M. A diadenosine 5’,5’’-P(1)P(4) tetraphosphate (Ap4A) hydrolase from Arabidopsis thaliana that is activated preferentially by Mn2+ ions. Acta Biochim. Pol. (2008) 55: 151-160
  5. Smirnova J., Zhukova L., Witkiewicz-Kucharczyk A., Kopera E., Olędzki J., Wysłouch-Cieszyńska A., Palumaa P., Hartwig A., Bal W. Quantitative electrospray mass spectrometry of zinc finger oxidation: the reaction of XPA zinc finger with H2O2. Anal. Biochem. (2007) 369: 226-231

 


 Molecular mechanisms of actions of biologically active metal ions

Group leader: Prof. Wojciech Bal
Staff: Dr. Arkadiusz Bonna, Dr. Grażyna Goch, Dr. Anna Staszewska, M.Sc. Agnieszka Belczyk, M.Sc. Ewa Kurowska, M.Sc. Katarzyna Piątek, M.Sc.Eng. Anna Maria Protas, M.Sc. Małgorzata Rózga, M.Sc. Aleksandra Witkiewicz-Kucharczyk (Ph.D. students)

 

Major research directions:
(a) the development of our proprietary methodology of recombinant protein purification based on a sequence-specific nickel(II)-dependent peptide bond hydrolysis reaction; (b) the effects of small molecules and metal ions on the stability and structure of zinc fingers; (c) the thermodynamic aspects of interactions of Alzheimer’s disease Aβ peptides with Cu(II) ions; (d) metal ion binding to albumin and structurally related peptides.

 

Research grants:

2008-2011 "New method of purification of recombinant proteins", (Ministry of Science and Higher Education)
2010-2012 "Competitive peptidic chelators as a tool for describing interactions of Cu(II) ion with Aβ peptide. Search for
                 novel molecular mechanisms of toxicity control in Alzheimer’s disease"
                 (Ministry of Science and Higher Education)
2010-2013 "Electrochemical biosensors for detection of activation of RAGE receptors – tools of cheap teranostics"
                 (Structural Funds, POIG Ministry of Sciences and Higher Education)
2010-2013 "Metal-dependent peptide hydrolysis. Tools and mechanisms for biotechnology, toxicology and supramolecular
                  chemistry" TEAM/2009-4/1 (Structural Funds, Fundation for Polish Science)

 

Selected publications:

  1. Sokołowska M., Pawlas K. , Bal W. Effect of common buffers and heterocyclic ligands on the binding of Cu(II) at the multimetal binding site in Human Serum Albumin. Bioinorg. Chem. Appl. (2010) - in press
  2. Bal W. , Protas A.M., Kasprzak K.S. Genotoxicity of Metal Ions: Chemical Insights, Metal Ions in Life Sciences Vol. 8, Metal Ions in Toxicology: Effects, Interactions, Interdependencies; eds. A. Sigel, H. Sigel, R.K.O. Sigel. RSC Press (2010) - in press
  3. Rózga M., Bal W. The Cu(II)/Aβ/HSA Model of Control Mechanism for Copper-related Amyloid Neurotoxicity. Chem. Res. Toxicol. (2010) 23: 298-308
  4. Rózga M., Kłoniecki M., Dadlez M., Bal W. A Direct Determination of the Dissociation Constant for the Cu(II) Complex of Amyloid Beta 1-40 Peptide. Chem. Res. Toxicol. (2010) 23: 336-340
  5. Krężel A., Kopera E., Protas A.M., Poznański J., Wysłouch-Cieszyńska A., Bal W. Sequence-specific Ni(II)-dependent Peptide Bond Hydrolysis for Protein Engineering. Combinatorial Library Determination of Optimal Sequences. J. Am. Chem. Soc. (2010) 132: 3355-3366
  6. Kurowska E., Bal W. Recent Advances in Molecular Toxicology of Cadmium and Nickel, Advances in Molecular Toxicology, Vol. 4, Ed. James C. Fishbein. Elsevier (2010) - in press.
  7. Rózga M., Protas A.M., Jabłonowska A., Dadlez M., Bal W. The Cu(II) complex of Ab40 peptide in ammonium acetate solutions. Evidence for ternary species formation. Chem. Commun. (2009) 11: 1374-1376
  8. Sokołowska M., Wszelaka-Rylik M., Poznański J., Bal W. Thermodynamic and spectroscopic determination of three distinct binding sites for Co(II) ions in Human Serum Albumin. J. Inorg. Biochem. (2009) 103: 1005-1013
  9. Piątek K., Hartwig A., Bal W. Physiological levels of glutathione enhance Zn(II) binding by a Cys4 zinc finger. Biochem. Biophys. Res. Commun. (2009) 389: 265-268

Modeling the relation between molecular structure and biological activity

Group leader: Dr. Jarosław Poznański

In parallel to our own studies numerous subjects are also studied in collaboration with other groups in IBB PAS.

  1. Analysis of TFE-induced fold of domain 4 of σ70 subunit of E. coli RNA polymerase (ECσ704) with the aid of heteronuclear NMR spectroscopy demonstrated that initially unfolded protein upon titration by TFE tends to adopt a structure of the canonical DNA-binding HLHTH fold.
  2. The new method of analysis of influence of salt mixture on the thermodynamics of organization of transcription complex enabled us to determine the corresponding equivalents for pure salt concentration.
  3. We have set up the method of immobilization of yeast cells in NMR tube, what enables 19F NMR studies on in vivo metabolism of fluorinated low-mass compounds.
  4. The method of chemical shift mapping coupled with docking procedures enabled us to point the individual binding sites on the HCV helicase surface.
  5. Analysis of the experimental data concerning inhibitory activity of a series of benzotriazole derivatives against CK2α kinase pointed the hydrophobic anion as the optimal ligand.



 

Group leader: Assoc. prof. Andrzej Dziembowski
Staff:

Current projects:

Research grants:

Selected publications: