Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Permanent URI for this collectionhttps://hdl.handle.net/11147/9
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Article Citation - WoS: 5Citation - Scopus: 5A Microrna-Regulated Transcriptional State Defines Intratumoral Cd8+t Cells That Respond To Immunotherapy(Cell Press, 2025) Tang, William W.; Battistone, Ben; Bauer, Kaylyn M.; Weis, Allison M.; Barba, Cindy; Fadlullah, Muhammad Zaki Hidayatullah; O'Connell, Ryan M.The rising incidence of advanced-stage colorectal cancer (CRC) and poor survival outcomes necessitate new and effective therapies. Immune checkpoint inhibitors (ICIs), specifically anti-PD-1 therapy, show promise, yet clinical determinants of a positive response are suboptimal. Here, we identify microRNA-155 (miR-155) as necessary for CD8+ T cell-infiltrated tumors through an unbiased in vivo CRISPR-Cas9 screen identifying functional tumor antigen-specific CD8+ T cell-expressed microRNAs. T cell miR-155 is required for anti-PD-1 responses and for a vital intratumor CD8+ T cell differentiation cascade by repressing Ship-1, inhibiting Tcf-1 and stemness, and subsequently enhancing Cxcr6 expression, anti-tumor immunity, and effector functions. Based on an underlying miR-155-dependent CD8+ T cell transcriptional profile, we identify a gene signature that predicts ICI responses across 12 diverse cancers. Together, our findings support a model whereby miR155 serves as a central regulator of CD8+ T cell-dependent cancer immunity and ICI responses that may be leveraged for future therapeutics.Article Blank Frame and Intensity Variation Distortion Detection and Restoration Pipeline for Phase-Contrast Microscopy Time-Lapse Images(Aves, 2024) Ucar, Mahmut; Iheme, Leonardo O.; Onal, Sevgi; Pesen-Okvur, Devrim; Yalcin-Ozuysal, Ozden; Toreyin, Behcet U.; Unay, DevrimIn this study, we propose a preprocessing pipeline for the detection and correction of distorted frames in time-lapse images obtained from phase-contrast microscopy. The proposed pipeline employs the average intensities of frames as a foundational element for the analysis. In order to evaluate the degree of correction required for intensity variance, a normalization technique is applied to the difference between the average intensity of a specific frame and the median average intensity of all frames within the study. Our restoration method increases the histogram similarity between the distorted and non-distorted frames, preserves trans-passing pixels in regions of interest, and mitigates the development of additional distortions. The efficacy of the proposed method was evaluated using 15 395 time-lapse image frames from 27 experiments using our own dataset and 830 time-lapse images from four different experiments obtained from the cell tracking challenge. The results of the validation demonstrate a high degree of numerical and visual accuracy of the proposed pipeline.Article Citation - WoS: 1Citation - Scopus: 2Trna Wobble Base Modifications and Boric Acid Resistance in Yeast: Boron-Resistant Deletion Mutants Induce the General Amino Acid Control Mechanism and Activate Boron Efflux(Pleiades Publishing, 2020) Uluisik, I.; Karakaya, H.C.; Koc, A.Abstract: Boric acid is essential for plants and has many vital roles in animals and microorganisms. However, its high doses are toxic to all organisms. We previously screened yeast deletion collections to identify boric acid-resistant and susceptible mutants to identify genes that play a role in boron tolerance. Here, we analyzed boron resistant mutants (elp1∆, elp3∆, elp6∆, ncs2∆, ncs6∆ and kti12∆) for their abilities to modulate the general amino acid control system (GAAC) and to induce boron efflux pump ATR1. The mutants analyzed in this study lack the genes that play roles in tRNA Wobble base modifications. We found that all of the boron resistant mutants activated Gcn4-dependent reporter gene activity and increased the transcript level of the ATR1 gene. Additionally, boron resistant cells accumulated less boric acid in their cytoplasm compared to the wild type cells upon boron exposure. Thus, our findings suggested that loss of wobble base modifications in tRNA leads to GAAC activation and ATR1 induction, which in turn reduced intracellular boron levels and caused boron resistance. © 2020, Pleiades Publishing, Inc.Article Citation - WoS: 19Citation - Scopus: 20Use of Micrornas in Personalized Medicine(Humana Press Inc., 2014) Avci, C.B.; Baran, Y.Personalized medicine comprises the genetic information together with the phenotypic and environmental factors to yield healthcare tailored to an individual and removes the limitations of the "one-size-fits-all" therapy approach. This provides the opportunity to translate therapies from bench to clinic, to diagnose and predict disease, and to improve patient-tailored treatments based on the unique signatures of a patient's disease and further to identify novel treatment schedules. Nowadays, tiny noncoding RNAs, called microRNAs, have captured the spotlight in molecular biology with highlights like their involvement in DNA translational control, their impression on mRNA and protein expression levels, and their ability to reprogram molecular signaling pathways in cancer. Realizing their pivotal roles in drug resistance, they emerged as diagnostic targets orchestrating drug response in individualized therapy examples. It is not premature to think that researchers could have the US Food and Drug Administration (FDA)-approved kit-based assays for miRNA analysis in the near future. We think that miRNAs are ready for prime time. © Springer Science+Business Media New York 2014.Article Citation - WoS: 3Citation - Scopus: 3Gene Reporter Assay To Validate Microrna Targets in Drosophila S2 Cells(Humana Press Inc., 2014) Akgül, B.; Göktaş, C.Bioinformatics programs have helped tremendously in identifying the targets of microRNAs, which are small noncoding RNAs that regulate gene expression posttranscriptionally. However, the partial complementarity between miRNAs and their targets hinders the accuracy of target prediction, necessitating the use of experimental validation procedures. Here, we describe a gene reporter assay typically used in our lab to validate putative miRNA-mRNA interactions in Drosophila S2 cells. © Springer Science+Business Media New York 2014.Review Citation - WoS: 10Citation - Scopus: 11An Update on Molecular Biology and Drug Resistance Mechanisms of Multiple Myeloma(Elsevier Ireland Ltd, 2015) Mutlu, P.; Kiraz, Y.; Gündüz, U.; Baran, Y.Multiple myeloma (MM), a neoplasm of plasma cells, is the second most common hematological malignancy. Incidance rates increase after age 40. MM is most commonly seen in men and African-American population. There are several factors to this, such as obesity, environmental factors, family history, genetic factors and monoclonal gammopathies of undetermined significance (MGUS) that have been implicated as potentially etiologic. Development of MM involves a series of complex molecular events, including chromosomal abnormalities, oncogene activation and growth factor dysregulation. Chemotherapy is the most commonly used treatment strategy in MM. However, MM is a difficult disease to treat because of its marked resistance to chemotherapy. MM has been shown to be commonly multidrug resistance (MDR)-negative at diagnosis and associated with a high incidence of MDR expression at relapse. This review deals with the molecular aspects of MM, drug resistance mechanisms during treatment and also possible new applications for overcoming drug resistance. © 2015 Elsevier Ireland Ltd.Article Citation - WoS: 17Citation - Scopus: 19Nacl Tolerance in Lycopersicon Pennellii Introgression Lines: Qtl Related To Physiological Responses(Kluwer Academic Publishers, 2011) Frary, A.; Keleş, D.; Pinar, H.; Göl, D.; Doğanlar, S.The growth and ion content of salt sensitive Lycopersicon esculentum Mill. cv. M82 and salt tolerant L. pennellii Correll accession LA716 were examined under both control and stress conditions (150 mM NaCl). L. esculentum grew more vigorously than L. pennellii under optimal conditions, however, L. pennellii was able to maintain its growth better than cultivated tomato when the plants were exposed to salinity. Sodium content of both L. esculentum and L. pennellii increased as a result of NaCl stress. In addition, both species showed reduced potassium and calcium content due to salinity. The physiological traits were also measured in a population of 52 L. pennellii introgression lines grown under both normal and stress conditions. A total of 311 quantitative trait loci (QTL) were identified for the studied traits: plant height, stem diameter, leaf number, leaf and root fresh and dry mass, and sodium, potassium and calcium contents. Some of the loci (124) were identified under both control and stress conditions while 86 QTL were identified only under non-stress conditions and 101 loci were identified only under NaCl stress.