Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Permanent URI for this collectionhttps://hdl.handle.net/11147/9
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Research Project Naif CD4+T hücrelerinden Th17 fenotipinde efektör T hücrelerinin oluşturulması ve Th17 farklılaşmasında rol oynayan mikroRNA'ların belirlenmesi(TÜBİTAK - Türkiye Bilimsel ve Teknolojik Araştırma Kurumu, 2014) Nalbant Aldanmaz, AytenTh17 T hücreleri IL-17 sitokini ekspres eden CD4+T hücrelerinin bir alt sınıfıdır. İnsan Th17 farklılaşması için gereken kültür koşulları, regülatör moleküller ve bu hücrelerin sürdürülebilirliği üzerindeki çalışmalar devam etmektedir. T hücre farklılaşmasında sitokinler, transkripsiyon faktörleri dışında mikroRNA gibi düzenleyici moleküllerin de etkili olabileceği önerilmektedir. Bu yüzden de, Th17 farklılaşmasında mikroRNA’ların rollerinin ortaya konması gerekmektedir. mikroRNA’lar (miRNAs) 17-23-nt uzunluğundaki RNA molekülleridir ve protein kodlayan genleri regüle ederler. Bu sebeple projenin amacı, insan periferal naif CD4+T hücrelerinden Th17 fenotipindeki T hücre alt grubunu oluşturmak ve Th17 fenotip farklılaşmasında rol oynayan mikroRNA’ları derin sekanslama metodu ile profillerini çıkarmaktırConference Object Citation - WoS: 3Citation - Scopus: 8Distinguishing Between Microrna Targets From Diverse Species Using Sequence Motifs and K-Mers(SCITEPRESS, 2017) Yousef, Malik; Khalifa, Waleed; Acar, İlhan Erkin; Allmer, JensA disease phenotype is often due to dysregulation of gene expression. Post-translational regulation of protein abundance by microRNAs (miRNAs) is, therefore, of high importance in, for example, cancer studies. MicroRNAs provide a complementary sequence to their target messenger RNA (mRNA) as part of a complex molecular machinery. Known miRNAs and targets are listed in miRTarBase for a variety of organisms. The experimental detection of such pairs is convoluted and, therefore, their computational detection is desired which is complicated by missing negative data. For machine learning, many features for parameterization of the miRNA targets are available and k-mers and sequence motifs have previously been used. Unrelated organisms like intracellular pathogens and their hosts may communicate via miRNAs and, therefore, we investigated whether miRNA targets from one species can be differentiated from miRNA targets of another. To achieve this end, we employed target information of one species as positive and the other as negative training and testing data. Models of species with higher evolutionary distance generally achieved better results of up to 97% average accuracy (mouse versus Caenorhabditis elegans) while more closely related species did not lead to successful models (human versus mouse; 60%). In the future, when more targeting data becomes available, models can be established which will be able to more precisely determine miRNA targets in hostpathogen systems using this approach.Article Citation - Scopus: 35Computational Prediction of Micrornas From Toxoplasma Gondii Potentially Regulating the Hosts' Gene Expression(Elsevier Ltd., 2014) Saçar, Müşerref Duygu; Bağcı, Caner; Allmer, JensMicroRNAs (miRNAs) were discovered two decades ago, yet there is still a great need for further studies elucidating their genesis and targeting in different phyla. Since experimental discovery and validation of miRNAs is difficult, computational predictions are indispensable and today most computational approaches employ machine learning. Toxoplasma gondii, a parasite residing within the cells of its hosts like human, uses miRNAs for its post-transcriptional gene regulation. It may also regulate its hosts' gene expression, which has been shown in brain cancer. Since previous studies have shown that overexpressed miRNAs within the host are causal for disease onset, we hypothesized that T. gondii could export miRNAs into its host cell. We computationally predicted all hairpins from the genome of T. gondii and used mouse and human models to filter possible candidates. These were then further compared to known miRNAs in human and rodents and their expression was examined for T. gondii grown in mouse and human hosts, respectively. We found that among the millions of potential hairpins in T. gondii, only a few thousand pass filtering using a human or mouse model and that even fewer of those are expressed. Since they are expressed and differentially expressed in rodents and human, we suggest that there is a chance that T. gondii may export miRNAs into its hosts for direct regulation.
