<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Spatial proteomics: from tissue organization to protein function"^^ . "Tumor heterogeneity is a term that refers to differences between tumors of the same type in\r\ndistinct patients as well as to differences observed between cells within a tumor. The later is\r\nknown as intratumoral heterogeneity (ITH) and is of high clinical relevance, since it directly\r\naffects the robustness of prognostic, diagnostics and prediction of biomarkers. Up to date ITH\r\nhas been mainly investigated at the genomic level. Sequencing of multiple regions from the same\r\ncancer specimen have revealed that within a single tumor several clones of cells with distinct\r\nmutational landscapes exist, likely as a consequence of clonal evolution. However, ITH can also\r\nbe driven by differences in the microenvironment that may rather be reflected in differential gene\r\nexpression or protein turnover than in genomic changes. Nevertheless, to what extent the ITH is\r\nmanifested on a proteome-wide scale remains largely unknown, mainly due to technical\r\nlimitations. To overcome these limitations an efficient protocol that allows for proteomic\r\nanalysis of limited amounts of formalin-fixed and paraffin-embedded (FFPE) material was\r\ndeveloped and employed to characterize the proteomic changes in hepatocellular carcinoma\r\n(HCC). First, by comparing neoplastic to the adjacent, non-neoplastic tissues, I defined\r\nproteomic features that distinguish tumor from peritumoral tissues. The analysis revealed a\r\ndecrease in abundances of various mitochondrial proteins including components of the NADH\r\ndehydrogenase complex I, possibly indicating the metabolic rearrangement in HCC.\r\nSubsequently, by analyzing different regions of HCC, I demonstrated the existence of a\r\nproteomic heterogeneity, beyond genetic variations, even in morphologically homogenous\r\nspecimens, which affects various biological processes. Several clinically relevant proteins were\r\nidentified as differentially expressed across the analyzed tumors or subject to ITH, thus\r\nunderlying the importance of ITH studies for biomarker discovery and diagnostic applications.\r\nIn the second part of my thesis, I focused on the functional characterization of gp210 – a\r\ntransmembrane component of the nuclear pore complex (NPC). In eukaryotic cells the nuclear\r\nenvelope constitutes a barrier separating the nucleoplasm and cytoplasm. The transport of\r\nmacromolecules between these compartments occurs through NPCs which form channels across\r\nthe inner and outer membrane of the nuclear envelope. Apart from regulating the\r\nnucleocytoplasmic transport, NPCs are also involved in the other cellular processes such as\r\nchromatin organization, regulation of gene expression or differentiation. The NPC is comprised\r\n8\r\nof multiple copies of around 30 proteins called nucleoporins (~1000 protein in total). While the\r\nstoichiometry of scaffold components is constant across cell lines, differences in the composition\r\nof peripheral sites have been observed. One example of a nucleoporin with a cell-type specific\r\nexpression is gp210. It is a transmembrane nucleoporin that associates with the NPC via its short\r\nC-terminal domain. The remaining larger part of the protein is localized within the perinuclear\r\nspace and it is not required for the interaction with the NPC. The luminal function of gp210 so\r\nfar has been linked to muscle cell differentiation but apart from this, its role remains largely\r\nunknown. In order to investigate the luminal function of gp210, I attempted to draft a map of\r\npotential interacting proteins. This was achieved by in-situ proximity labeling combined with\r\nmass spectrometry-based proteomics using the so-called BioID approach. Data obtained in\r\nBioID experiments indicate a functional link between gp210 and endoplasmic reticulum (ER)\r\nrelated biological functions. I have identified multiple factors involved in the regulation of ER\r\nstress and several proteins involved in glycophosphatidylinositol anchor attachment."^^ . "2019" . . . . . . . "Katarzyzna"^^ . "Buczak"^^ . "Katarzyzna Buczak"^^ . . . . . . "Spatial proteomics: from tissue organization to protein function (PDF)"^^ . . . "PhD_Thesis_Katarzyna_Buczak.pdf"^^ . . . "Spatial proteomics: from tissue organization to protein function (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Spatial proteomics: from tissue organization to protein function (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Spatial proteomics: from tissue organization to protein function (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Spatial proteomics: from tissue organization to protein function (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Spatial proteomics: from tissue organization to protein function (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #25909 \n\nSpatial proteomics: from tissue organization to protein function\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . .