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nencki.gov.pl » Working Groups »
Department of Biochemistry

  Head
Prof. Sławomir PIKUŁA
e-mail: s.pikula@nencki.gov.pl

Department of Biochemistry was established in February 2007 after the fusion of Department of Cellular Biochemistry and Department of Muscle Biochemistry, and is composed of nine laboratories including the two new ones opened at the beginning of 2007 (Dobrzyń and Zabłocki). The research programs carried out in the Department are generally focused on molecular regulation of cell fate under normal and pathological conditions as well as elucidating molecular mechanisms of functioning of the contractile and motile apparatuses of muscle and non-muscle systems. We are interested in delineating signaling pathways responsible for cell death and cellular senescence of normal and cancer cells (Sikora’s and Duszyński’s laboratories) as well as lipid metabolism in normal and pathological conditions (Dobrzyń’s laboratory). The mechanisms of the protective action of potassium channel openers on cardiac and skeletal muscle mitochondria are also subject of our studies, as they can have serious application in protecting against heart damage (Szewczyk’s laboratory). Programs aimed at new ways of taking advantage of old targets in chemotherapy are focused on thymidylate synthase post-translational modifications and capacity to bind RNA and suppress translation (Rode’s laboratory). A particular attention is put on the role of mitochondria in apoptosis and calcium homeostasis as well as the effects of fatty acids and their derivatives on mitochondrial energy-coupling processes (Duszyński’s, Szewczyk’s, Zabłocki’s and Sikora’s laboratories). Calcium homeostasis in normal and pathological states (Duszyński’s and Zabłocki’s laboratories), with special emphasis to various calcium-binding proteins, including mammalian and plant annexins, their structure, function and role in human diseases, is also investigated (Pikuła’s laboratory). The studies on motile systems are mainly focused on structure-function relationships in motor proteins as well as regulators of their activities (Rędowicz’s and Kasparzak’s laboratories). Heterogeneity of prion protein complexes and functional interaction of prions with microtubular system is also studied (Rędowicz’s laboratory). In the recently established Laboratory of Cell Signaling and Metabolic Disorders (Dobrzyń’s) the research is focused on the molecular mechanisms of lipotoxicity with special emphasis on lipid-induced insulin resistance and the role of fatty acids in the regulation of gene expression.

 

Major recent achievements of the laboratories associated in the previous Department of Cellular Biochemistry and the Department of Muscle Biochemistry include:

  • identification of a GTP-sensitive domain in the human annexin A6 molecule that is most probably responsible for the formation of voltage dependent low-specificity ion channels by the protein under certain pathophysiological conditions (Pikuła’s laboratory);

  • establishment of the role of calcium release-activated channels, CRACs, in protecting Jurkat cells against calcium overload in transient episodes of energy stress and possible role of mitochondrial calcium pool in this process (Duszyński’s laboratory);

  • finding of high expression of enzymes involved in thymidylate biosynthesis in developmentally arrested larvae of parasitic (Trichinella spiralis and T. pseudospiralis) and free-living (Caenorhabditis elegans) nematodes, suggesting global cell cycle arrest (Rode’s laboratory);

  • elucidation of molecular mechanisms of mitotic catastrophe and cellular senescence as a cell fate of cancer cells resistant to apoptosis induced by many factors and demonstrating that curcumin, a natural dye, is a potent inducer of these processes (Sikora’s laboratory);

  • the effects of quinine on cardiac mitochondrial ATP-regulated potassium channel as trigger and effector in myocardial ischemic preconditioning as a result of the interaction of the drug with the mitochondrial sulfonylurea receptor (Szewczyk’s laboratory).

  • characterization of the effects of prion protein on microtubule formation and elucidation of the mechanisms of early steps of salt-induced actin polymerization (Rędowicz’s laboratory)

  • production and purification of a pseudo-heterodimeric kinesin Ncd, in which each of the subunits can be independently genetically manipulated (Kasprzak’s laboratory).

  • identification of nucleotide receptors participating in the impaired calcium homeostasis in dystrophic mouse myoblasts (Zablocki’s Laboratory).

The field of expertise of members of the Department is powered by many experimental units, including the following. The cytometry unit is equipped with a Beckton-Dickinson flow cytometer FACSCalibur, cell sorter FACSAria and CompuCyte laser scanning iCys. FACS flow is a typical flow cytometer but iCys is the versatile analysis platform that combines precise quantification of laser-based cytometry, high content of automated imagine analysis, and visualisation of inverted microscopy. The electrophysiological unit allows identification and characterization of ion channel activity of proteins. The Till Photonics unit is a fluorescence microscopy system (TILL Photonics GmbH), which can be used for a variety of different applications in living cells such as measurement of rapidly changing intracellular ion concentrations. InGenius Bio Imaging from Syngene serves for documentation and analysis of all electrophoresis gels, spots, blots, colonies, and films visible in UV and visible light. Its  software for image analysis makes possible band quantification and molecular weight determination, and rapid automatic analysis of gels, multiple layers of wells or multiple gels.

 

Selected publications of the Department

Jarmuła A., Cieplak P., Krygowski T.M., Rode W. (2007) The effect of 5-substitution in the pyrimidine ring of dump on the interaction with thymidylate synthase: Molecular modeling and QSAR. Bioorg. Med. Chem. 15: 2346-2358

Kicińska A., Swida A., Bednarczyk P., Koszela-Piotrowska I., Choma K., Dołowy K., Szewczyk A., Jarmuszkiewicz W. (2007) ATP-sensitive potassium channel in mitochondria of the eukaryotic microorganism Acanthamoeba castellanii. J. Biol. Chem. 282: 17433-17441

Schönfeld P., Wojtczak L. (2007) Fatty acids decrease mitochondrial generation of reactive oxygen species at the reverse electron transport but increase it at the forward transport. Biochim Biophys Acta 1767: 1032-1040

Sobczak M., Kocik E., Rędowicz M.J. (2007) A novel Amoeba proteus 120-kDa actin-binding protein with only one filamin repeat and a coiled-coil region. Biochem. Cell Biol. 85: 22-31

Kirilenko A., Pikuła S., Bandorowicz-Pikuła J. (2006) Effects of mutagenesis of W343 in human annexin A6 isoform 1 on its interaction with GTP: nucleotide-induced oligomer formation and ion channel activity. Biochemistry 45: 4965-4973

Reuther C., Hajdo Ł., Tucker R., Kasprzak A. A., Diez S. (2006) Biotemplated nanopatterning of planar surfaces with molecular motors. Nano Lett. 6: 2177-2183

Sikora E., Bielak-Zmijewska A., Magalska A., Piwocka K., Mosieniak G., Kalinowska M., Widlak P., Cymerman I. A., Bujnicki J.M. (2006) Curcumin induces caspase-3-dependent apoptotic pathway but inhibits DNA fragmentation factor 40/caspase-activated DNase endonuclease in human Jurkat cells. Mol. Cancer Ther. 5: 927-934

Yeung D., Zabłocki K., Jiang T., Arkle S., Brutkowski W., Brown J., Lochmuller H., Simon J., Barnard E.A., Górecki D.C. (2006) Increased susceptibility to ATP via alteration of P2X receptor function in dystrophic mdx mouse muscle cell. FASEB J.  20: 610-620               

Wawro B., Khaitlina S. Y., Galińska-Rakoczy A., Strzelecka-Gołaszewska H. (2005) Role of actin DNase-I-binding loop in myosin subfragment 1-induced polymerization of G-actin. Implications to the polymerization mechanism. Biophys. J. 88: 2883-2896

Zabłocki K., Szczepanowska J., Duszyński J. (2005) Extracellular pH modifies mitochondrial control of capacitative calcium entry in Jurkat cells. J. Biol. Chem. 280: 3516-3521          

Zhang L., Balcerzak M., Radisson J., Thouverey C., Pikuła S., Azzar G., Buchet R. (2005) Phosphodiesterase activity of alkaline phosphatase in ATP-initiated Ca2+ and phosphate deposition in isolated chicken matrix vesicles. J. Biol. Chem. 280: 37289-37296



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Published at: 2007-11-22 11:15
 

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