Master Degree / Yüksek Lisans Tezleri

Permanent URI for this collectionhttps://hdl.handle.net/11147/3008

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Department: search.filters.department.Thesis (Master)--İzmir Institute of Technology, Molecular Biology and GeneticsSubject: search.filters.subject.Molecular biology

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Now showing 1 - 3 of 3
  • Master Thesis
    Identification of Neuroinflammatory Markers in a Mouse Model With a Deficiency of Neu1
    (01. Izmir Institute of Technology, 2024) Seyrantepe, Volkan; Seyrantepe, Volkan; Seyrantepe, Volkan; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
    Lysosomal neuraminidase 1 is responsible for sialic acid removal from oligosaccharides and glycoconjugates. Neu1 sialidase forms enzyme complex with protective protein cathepsin A, and glycosidase β-galactosidase. Mutations in Neu1 sialidase cause sialidosis, and Neu1-/- mice show symptoms of sialidosis patients. GM3 ganglioside is defined as substrate of lysosomal sialidase in vitro, and marked increase in GM3, GD3, and GM4 ganglioside levels in brain, spleen and liver autopsy tissues of sialidosis patients. Additionally, it was monitored that Neu1 has regulatory roles in immune response; expression of interleukins, activation of Toll-like receptor, and production of NF-kB in immune cells. However, relationship between inflammatory pathways and secondary lipid metabolisms in Neu1 sialidase deficiency remains unclear. Here, we aimed to investigate secondary lipid alterations and inflammatory response in tissues of Neu1-/- mice. In this study, lipidomic, molecular, histological and immunohistochemical analyses were performed in brain, spleen and kidney tissues of 2- and 5-month-old Neu1-/- mice. Decreasing levels of secondary lipids (phosphotidylcholine, phosphatidylethanolamine, and phosphotidylinositol) and elevated levels of pro-inflammatory cytokines, glycoconjugate accumulations, morphological degenerations, oligodendrocyte and neuronal loss, astrogliosis, and microgliosis were observed in brain, spleen and kidney of 2- and 5-month-old Neu1-/- mice. In the light of our findings, reduced levels of glycerophospholipids may be considered as biomarkers of activated inflammatory response in Type II sialidosis mice model. In the future studies, novel therapeutic strategies can target these altered glycerophospholipids, and their regulation can be crucial for alleviation of pathogenesis in sialidosis patients.
  • Master Thesis
    Identification of Novel Notch Target Genes That Are Mediators of Notch in Inducing Epithelial To Mesenchymal Transition and Migration/Invasion
    (Izmir Institute of Technology, 2016) Küçükköse, Cansu; Yalçın Özuysal, Özden; Yalçın Özuysal, Özden; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
    Notch signaling has first been described in murine mammary gland by the proviral integration of mouse mammary tumor virus (MMTV) into the Notch4 locus (Int3 locus) which resulted expression of constitutively active form of Notch4 and transformation of mammary epithelial cells. Notch1 is highly expressed in breast cancer and constitutively active form of Notch1 induces neoplasm. In breast cancer, overexpression of active Notch1 receptor (NICD) promotes epithelial-mesenchymal transition (EMT) via Snail induction which demonstrates the role of Notch signaling in induction of metastasis through EMT. However, the downstream mediators of Notch in EMT, migration and invasion processes are still elusive. In this study, we hypothesized that Notch signaling induces EMT and migration via regulating one or more of the seven candidate genes that are SEMA6D, SEMA3C, CXCR7, CXCL14, CCL20, HMGA2 and CYR61 which were shown to be differentially regulated by Notch signaling in breast cells in microarray data. The candidate genes are involved in EMT and migration in different cell types and tissues. We showed that Notch1 activation in normal breast epithelial cell line MCF10A significantly increased both mRNA and protein expressions of SEMA6D and CYR61 while it significantly reduced SEMA3C and HMGA2 mRNA levels. Notch inhibition led to significant reduction in mRNA expression of CYR61, CCL20 and HMGA2 and protein expression of CYR61 only, while the rest of candidate genes were affected slightly in breast cancer cell line, MDA-MB-231. We chose SEMA6D for further investigation because there is no data indicating the role of SEMA6D in breast cancer in the literature. SEMA6D could be mediator of Notch signaling to induce EMT because it partially rescues negative effect of Notch inhibition on EMT markers. Notch independent effect of SEMA6D suggested that SEMA6D may be involved in inhibiting EMT whereas, it induced migration and cell viability in MDA-MB-231 cell line.Further analysis is required to reveal the role of SEMA6D in EMT and migration.
  • Master Thesis
    Deciphering 5-Fluorouracil Mediated Molecular Mechanisms Required for Cell Death
    (Izmir Institute of Technology, 2011) Can, Geylani; Baran, Yusuf; Baran, Yusuf; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
    The chemotherapy agent 5-Fluorouracil (5-FU) is an antimetabolite that has been in use to treat several cancers for decades. In cells, it is converted into three distinct fluoro-based nucleotide analogues which interfere with DNA-synthesis and repair leading to impairment of the genome and, eventually apoptotic cell death. Current knowledge also state that 5-FU induced damage is signaling through a p53-dependent induction of death inducing complex (DISC) formation and further caspase-8 activation in certain cell types and members of the TNF-receptor family has been proposes to be required for the process. Here, we introduce calcium (Ca2+) as a messenger for p53 activation in the cellular response triggered by 5-FU. Using a combination of pharmacological and genetic approaches, we show that treatment of cultured colon carcinoma cells stimulates entry of extracellular Ca2+ through L-type plasma membrane channels and that this event direct posttranslational phosphorylation of at least two specific p53 serine residues (ser15 and ser33) by means of Calmodulin (CaM) activity. Obstructing this pathway by the Ca2+-chelator BAPTA or by two different inhibitors of CaM efficiently blocks 5-FU-induced cell death. The fact that a widely used therapeutic drug, such as 5-FU, is signaling by these means could provide new therapeutic intervention points, or specify new combinatorial treatment regimes.