<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Role of Phosphoinositides in Cellular Polarity and Immunity"^^ . "Cell polarity describes the asymmetric distribution of proteins, RNA, organelles and\r\nlipids. One of the best studied models of polarity are epithelial cells. They form the barriers that\r\nseparate and protect the organism from the outside environment. Establishment and maintenance\r\nof polarity is ensured through a highly complex network of proteins and lipids that mediate\r\nasymmetry through trafficking processes and reorganization of the cytoskeleton. One of the key\r\nplayers in polarity are phosphoinositides, phosphorylated forms of the lipid phosphatidylinositol.\r\nIn this thesis I investigated the role of one such phosphoinositide, PI(3)P, on cellular polarity and\r\nimmunity in human intestinal epithelial cells.\r\nIn my work I used established methods to evaluate the role of PI(3)P in human intestinal\r\nepithelial cells. These three methods were (1) the use of specific inhibitors targeting VPS34 (2)\r\nthe development of cell lines depleted of kinases and phosphatases needed for PI(3)P biogenesis\r\nand (3) on demand depletion of PI(3)P from endosomes using a chemical dimerizer system. Each\r\nof these methods were evaluated both for their ability to modulate PI(3)P levels and for their\r\nimpact on cellular polarity and immune response. While I could demonstrate that all three\r\nmethods successfully modulated PI(3)P levels the chemical dimerizer (AP21967) interferes with\r\npolarity and immunity itself and we require a new dimerizer before conclusions can be made\r\nusing this method. Interestingly, I determined that reduced PI(3)P levels, either by chemical\r\ninhibition or knock-down of the kinase VPS34, impaired cellular polarity in T84 cells indicating\r\na critical role of PI(3)P in the polarity program. Additionally, knock-down of the PI(3)P\r\nmetabolizing enzymes VPS34 and MTM1 showed interesting results for IFNλ production upon\r\nreovirus infection. IFNλ production in MTM1 and VPS34 knock-down cells is increased and\r\ndecreased respectively. This could be due to the previously reported PI(3)P dependent TLR3\r\nsorting adaptor WDFY1 and should be further investigated.\r\nIn parallel I also created a novel viral vector system in our lab. This viral vector is based\r\non the BacMam system which are baculovirus based vectors with a large cargo capacity. The\r\nBacMam was initially modified with an S/MAR sequence to allow for its persistence in cells. The\r\nvector was then further modified to allow expression of reporter genes. Both vectors were shown\r\nto be fully functional and will provide a valuable tool for future projects."^^ . "2018" . . . . . . . "Christian"^^ . "Kischnick"^^ . "Christian Kischnick"^^ . . . . . . "Role of Phosphoinositides in Cellular Polarity and Immunity (PDF)"^^ . . . "PhD Thesis - Christian Kischnick - PDF_A.pdf"^^ . . . "Role of Phosphoinositides in Cellular Polarity and Immunity (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Role of Phosphoinositides in Cellular Polarity and Immunity (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Role of Phosphoinositides in Cellular Polarity and Immunity (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Role of Phosphoinositides in Cellular Polarity and Immunity (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Role of Phosphoinositides in Cellular Polarity and Immunity (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #25144 \n\nRole of Phosphoinositides in Cellular Polarity and Immunity\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .