Department of Cell Biology
Head: Dr. Sc. Katarzyna Kwiatkowska
e-mail: k.kwiatkowska@nencki.gov.pl
The research interests of the Department of Cell Biology encompass the fundamental issues of plasma membrane receptor activation and signal transduction under physiological and pathological conditions. Our activities are directed to study signalling cascades and the regulation of gene expression associated with (i) tumor pathology, (ii) immuoresponses, (iii) endocytosis and phagocytosis, (iv) folding of cytoskeletal proteins and cytoskeleton reorganization. Approaches range from molecular biology to electrophysiology and whole organism physiology. The ongoing research projects in the Department are focused on:
• Molecular mechanisms regulating endocytosis and degradative pathways investigated in diff erent cell types undergoing gene silencing (RNAi) and stimulation. Characterization of the products encoded by the genes cloned by us in a model unicellular eukaryote Paramecium octaurelia and indispensable for endosome/phagosome formation, sorting and membrane traffi cking including Rab7 and its eff ectors. Studies are performed at the protein and cellular levels including proteomics, molecular biology techniques, confocal/electron microscopic immunocytochemistry and 3D imaging (Head of Laboratory – Elżbieta Wyroba)
• Identifi cation of signalling pathways, transcriptional and epigenetic regulation of gene expression underlying brain tumour pathogenesis and neuroinfl ammation; development of RNAi and recombinant interfering peptide technology-based molecules to study tumour invasion and tumour-host interactions in vitro and in vivo (the laboratory is a member of Polish-French GDRE); development of computational methods and databases that integrate ChIP assays with DNA microarray and high-throughput sequencing technologies enabling the profi ling of wholegenome histone modifi cations and transcription factor occupancy sites under brain inflammation (Head of Laboratory – Bożena Kamińska-Kaczmarek)
• Investigations of the function of proteins involved in folding of cytoskeletal proteins, particularly actin and tubulin, in protists and mammalian cells and its role in physiological cell responses; proteomic and functional analysis of proteins involved in ciliogenesis in protozoan cells and immortalized mammalian cell lines by genetic engineering, immunochemical, immunocytochemical and ultrastructural characteristics; the role of extracellular factors in dynamics of actin cytoskeleton in Amoeba proteus with the identifi cation and determination of the function of actin binding proteins; the function of RhoA/ROCK pathway and calcium signal in the actin skeleton arrangement; the role of actin and unconventional myosins in cell migration; electrophysiological patch-clamp investigations characterizing the structure and function of mechanosensitive ion channels in Escherichia coli membrane (Head of Laboratory – Stanisław Fabczak)
• Studies on the mechanisms of signal generation by Fcγ and TLR4 immunoreceptors at the onset of phagocytosis and LPS recognition in macrophages and monocytes. The essential approach is to examine how activated receptors initiate a cascade of events leading to reorganisation of membrane constituents, activation of tyrosine kinases and phosphoinositide kinases. In particular, this group is focussed on: the involvement of plasma membrane rafts in receptor signalling, the role of the sphingomyelin cycle and ceramide generation in the transduction of signals by the receptors, the role of PI P2 in modulation of submembrane cytoskeleton and cytokine generation (Head of Laboratory – Andrzej Sobota)
• Revealing the role of the Grainyhead-like (GRHL) transcription factors in signal transduction in mammalian cells. The studies are focused on understanding the regulation of gene expression by GRHL and regulation of the activity of GRHL proteins. Analysis of phenotypes of mouse strains carrying mutations in the Grhl genes is performed. The investigations aim at mechanisms of GRHL function in health and disease; role of the GRHL factors in neural tube closure; involvement of the planar cell polarity pathway in wound healing. (Head of Laboratory – Tomasz Wilanowski) established in our Department in 2009.
Selected publications:
Kwiatkowska A., Kijewska M., Lipko M., Hibner U., Kamińska B. (2011) Downregulation of Akt and FAK phosphorylation reduces invasion of glioblastoma cells by impairment of MT1-MMP shuttling to lamellipodia and down-regulates MMPs expression. Biochimica et Biophysica Acta, 1813: 655-667.
Liu L., Wyroba E., Satir B.H. (2011) RNAi knockdown of parafusin inhibits the secretory pathway. European Journal of Cellular Biology, 90: 844-853.
Koprowski P., Grajkowski W., Isacoff E.Y., Kubalski A. (2011) Genetic screen for potassium leaky small mechanosensitive channels (MscS) in E. coli: recognition of cytoplasmic beta domain as a new gating element. Journal of Biological Chemistry, 286: 877-888.
Boglev Y., Wilanowski T., Caddy J., Parekh V., Auden A., Darido C., Hislop N.R., Cangkrama M., Ting S.B., Jane S.M. (2011) The unique and cooperative roles of the Grainy head-like transcription factors in epidermal development refl ect unexpected target gene specifi city. Developmental Biology, 349: 512–522.
Józefowski S., Czerkies M., Łukasik A., Bielawska A., Bielawski J., Kwiatkowska K., Sobota A. (2010) Ceramide and ceramide 1-phosphate are negative regulators of TNF-α production induced by lipopolysaccharide. Journal of Immunology, 185: 6960-6973.
Tyburczy M.E., Kotulska K., Pokarowski P., Mieczkowski J., Kucharska J., Grajkowska W., Roszkowski M., Jóźwiak S., Kamińska B. (2010) Novel proteins regulated by mTOR in subependymal giant cell astrocytomas of patients with tuberous sclerosis complex a and new therapeutic implications. American Journal of Pathology, 176: 1878-1890.
