Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/5799
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Master Thesis RNA Etkileşimlerinin İn Silico Analizi(Abdullah Gül Üniversitesi, Fen Bilimleri Enstitüsü, 2024) Orhan, Mehmet Emin; Demirci, Müşerref Duygu SaçarMany supervised machine learning models have been developed for the classification and identification of non-coding RNA (ncRNA) sequences. These models play a significant role in the diagnosis and treatment of various diseases. During such analyses, positive learning datasets typically consist of known ncRNA examples, some of which may even be confirmed with strong experimental evidence. However, there is no database of validated negative sequences for ncRNA classes or standardized methodologies for generating high quality negative samples. To overcome this challenge, a new method for generating negative data called the NeRNA (Negative RNA) method has been developed in this study. NeRNA generates negative sequences using known ncRNA sequences and their octal representations, similar with frame shift mutations found in biology but without base deletions or insertions. In this thesis, the NeRNA method was tested separately with four different ncRNA datasets, including microRNA (miRNA), transfer RNA (tRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). Additionally, a species-specific case study was conducted to demonstrate and compare the performance of the study's miRNA predictions. The results of 1000-fold cross-validation on machine learning algorithms such as Decision Trees, Naive Bayes, Random Forest classifiers, and deep learning algorithms like Multilayer Perceptrons, Convolutional Neural Networks, and Simple Feedforward Neural Networks showed that models developed using datasets generated by NeRNA exhibited significantly high prediction performance. NeRNA has been published as an easy-to-use, updatable, and modifiable KNIME workflow, along with example datasets and required extensions that can be downloaded and utilized. NeRNA is designed specifically as a powerful tool for RNA sequence data analysis.Master Thesis Tasarlanmış Mikroorganizmalar ile Katma Değeri Yüksek Karotenoidlerin Biyosentezi(Abdullah Gül Üniversitesi, Fen Bilimleri Enstitüsü, 2024) Arslansoy, Nuriye; Fidan, ÖzkanCarotenoids are pigment molecules that play an important role in coloring plants, algae, and other organisms. These molecules exhibit various biological activities such as anticancer, antiviral and antioxidant activities. They have a huge market size and are mainly used in the food, feed, and cosmetic industries. The current supply chain for carotenoids is mostly relied on the extraction from plants and/or chemical synthesis for certain carotenoids. However, these strategies have various bottlenecks and disadvantages such as being affected by climate change, more difficult and costly extraction processes, and environmental issues. These can be overcome with microbial biosynthesis, which not only addresses the previous problems but also provides advantages of producing in a short time and scale-up for industrial production. In this research, we aimed to biosynthesize the high value-added carotenoids by engineered microorganisms. The genome of a native producer of zeaxanthin diglucoside, identified as endophytic Pseudomonas sp. 102515, was first edited by CRISPR-Cas9 to knock out zeaxanthin glucosyltransferase (CrtX), lycopene β-cyclase (CrtY) and beta-carotene hydroxylase (CrtZ). This led to ΔcrtX, ΔcrtY and ΔcrtZ mutant strains of Pseudomonas sp. 102515. On the other hand, overexpression plasmids carrying crtW, CaZEP and CaZEP-CaCCSm40 genes were constructed and transformed to ΔcrtX mutant to synthesize astaxanthin, violaxanthin and capsanthin/capsorubin. HPLC analysis of extracts from mutant strains and overexpression strains revealed that all the engineered strains produced the corresponding carotenoids such as zeaxanthin, β-carotene, and lycopene. Thus, this study paved the way for the biosynthesis of valuable carotenoids in the engineered endophytic bacteria.Master Thesis COVID-19 Virüs Pandemisinde Haftalık Döngünün Kökeni ve Sosyo-Ekonomik Faktörlerle İlişkisinin Araştırılması(Abdullah Gül Üniversitesi, Fen Bilimleri Enstitüsü, 2024) Yağmur, İsmail Emre; Ercan, AltanThe Covid-19 virus, which started in China in 2019 and affected the whole world, has caused a global pandemic. Looking at the worldwide data of this pandemic, the number of daily cases appears to have a weekly cycle that is underestimated as an artifact of the number of daily tests administered. In this thesis study, a new model is developed to calculate the daily infection numbers from daily case numbers by using the Weibull distribution and the natural characteristics of the COVID-19 virus. According to the results obtained, it is found that the number of daily cases has a real weekly cycle. It has been determined that the daily infection numbers calculated in this weekly cycle are minimum on weekdays. According to the analysis by the new methos, these weekly minimums are controlled by socio-economic factors such as human development index and annual national income per capita. During the ascending and descending phases of the pandemic, the weekly minimum shifts from Monday to Friday, exposing the presence of two separate environments for the transmission of the virus among people: working and social. Moreover, the data reveal a variable rather than a fixed reproduction number. As a result, the model we developed in this study successfully identifies the socio-economic factors as the effectors of the progression of the pandemic by taking into account the time of infection for the first time in the literature and is expected to guide the future pandemic studies and pandemic, itself.Master Thesis Geleneksel Gıda Ürünlerinden İzole Edilen Laktik Asit Bakterilerinin Probiyotik Özelliklerinin Belirlenmesi(Abdullah Gül Üniversitesi, Fen Bilimleri Enstitüsü, 2023) Yiğit, Mehmet Burak; Aydın, Aysun CebeciProbiotics are microorganisms that live in our bodies and positively affect health when consumed regularly. One of the ways to have a healthy body is to have a healthy microbiota. Because of that, the importance given to the consumption of probiotic foods among the public is increasing. Since probiotics are especially abundant in fermented and traditional foods, consuming these foods is vital to have a healthy microflora. In this thesis, probiotic potentials of bacteria isolated from tarhana, einkorn sourdough, Turkish and Bulgarian-type boza and pickled beetroot foods were investigated, and obtained results were discussed. Based on acid and bile salt tolerance tests, MRS ES-2-3-7-11-12-17, MRS PT-2-14-16, MRS N-1, MRS EB-3, MRS T-1, M17 N-2 -3-4 showed higher viability in acidic environments (pH 2.0 and 3.0) than the control groups, M17 N-3-4 and M17 TB-1-2 strains showed higher viability at 0.3% and 0.5% bile salt conditions than other strains. For 10 strains which are selected for further tests, in the adhesion to Caco-2 cells, MRS ES-3, MRS N-1, MRS T-2, M17 BB-7, M17 N-2 and M17 N-3 showed over 35% adhesion, especially, MRS N-1 and M17 N-2 showed over 85% adhesion to Caco-2 cells. For the antimicrobial activity test, ES-3 strain showed limited effect on S. aureus ATCC 6538 and K. pneumoniae ATCC 4352 pathogens, while other strains showed no inhibitory effect on pathogens. Finally, according to the results of 16S rRNA sequencing, it was determined that MRS ES-3, ES-7, PT-14 strains belonged to L. plantarum, MRS ES-11 strain belonged to L. brevis, M17 BB-7 strain belonged to E. faecium and M17 TB-2 strain belonged to E. durans species.Master Thesis 3D Biyobaskı Parametrelerinin PCL İskelesinin Basılabilirliği ve Mekanik Davranışı Üzerindeki Etkisi(Abdullah Gül Üniversitesi / Fen Bilimleri Enstitüsü, 2023) Ceylan, Saniye Aylin; İşoğlu, İsmail AlperPolycaprolactone (PCL) is a synthetic polymer that exhibits desirable properties such as biodegradability, tolerable mechanical properties, and biocompatibility for a diverse range of tissue engineering applications. In this study, we analyzed the effects of polymer concentration (10%, 25%, 50% and 75% w/v), solvent effect (dichloromethane, chloroform and acetic acid), and device parameters (pressure, speed, nozzle-surface distance, nozzle gauge, infill density) on printed scaffolds fabricated through 3D Bioprinting. Scanning electron microscopy (SEM) and optical microscopy were used to assess printability, and uniaxial tensile testing was performed to evaluate mechanical behavior. The aim of this study was to investigate the effects of different printing speeds (5 mm/s, 10 mm/s, and 15 mm/s) on the mechanical properties of PCL_DCM and PCL_CF scaffolds. The scaffolds printed at the lowest speed exhibited the highest ultimate tensile strength (UTS) values. Scaffolds printed at 5 mm/s with the highest printing pressure (480 kPa) demonstrated a remarkably high Young's modulus of 39.69 MPa and a UTS value of 6.4 for PCL_DCM, as well as Young's modulus of 26.80 MPa and a UTS value of 6.3 MPa for PCL_CF. Additionally, we investigated the influence of polymer concentrations (50% and 75%) and infill densities (50%, 70%, and 90%). The results showed that increasing the infill density and using a lower concentration (50%) led to improvements in Young's modulus and UTS values for both PCL_DCM and PCL_CF scaffolds. These results highlight the importance of carefully controlling printing parameters to optimize the mechanical properties of the printed scaffolds.Master Thesis Işık ile Çapraz Bağlanabilen Aljinat Bazlı Tannik Asit ile Güçlendirilmiş Biyomürekkep Hidrojellerin Hazırlanması ve Karakterizasyonu(Abdullah Gül Üniversitesi / Fen Bilimleri Enstitüsü, 2023) Demirci, Enes Hamdi; İşoğlu, Sevil Dinçer; Demirtaş, Tuğrul TolgaAlginate is a commonly used biopolymer in bioprinting applications. However, alginate-based bioinks have some mechanical limitations for printing purposes. Also, existing methacrylation methods are time consuming and have low methacrylation efficiencies. Based on these facts, we focused on enhancing mechanical strength of alginate within the scope of this thesis. To do this, we applied microwave irradiation during methacrylation process of alginate and compared the efficiencies between conventional and microwave irradiation. Here, we report a significantly faster and more effective method for the controlled synthesis of methacrylated alginate (Alg-MA) by microwave energy (250 W) with approximately 80% degree of methacrylation (DM) even with a very low amount of metyhacrylation agent (aminoethyl methacrylate (AEMA)). Rheological and mechanical analyses showed that Alg-MAs synthesized by microwave irradiation allowed the formation of more elastic and stronger hydrogels with very high stability than the ones synthesized by the conventional method. Additionally, we combined these hydrogels with tannic acid by a second cross-linking in order to improve their mechanical strength and tissue integration ability. Addition of TA provided hydrogels very good mechanical strength and also antibacterial characteristics towards gram-positive and gram-negative bacteria. As a conclusion, hydrogels with mechanically superior properties and antibacterial characteristics were obtained by MW-assisted methacrylation and physical cross-linking by TA.Master Thesis 32-mer MaSP1 Geninin pBbB6c Plazmid Vektörüne Klonlanması ve Escherichia Coli NEB 10-beta'ya Transformasyonu(Abdullah Gül Üniversitesi, Fen Bilimleri Enstitüsü, 2023) Benk, Ruveyda; Ortakcı, Fatih; Öz, YahyaThe main purpose of my thesis was to clone Masp1 spider silk protein encoding gene from dragline type spider into E.coli NEB 10-beta organism. The recombinant microbial production of spider silk protein and converting it into a fiber format would ultimately produce a biomaterial also called as biosteel with high toughness and elasticity whereas low density compared to Kevlar, steel and carbon fiber. For this purpose, the gene encoding the dragline spider protein (MaSP1) was cloned into E. coli NEB 10-beta using recombinant molecular methods. First, 8-mer MaSP1 was synthesized and cloned via pGSI high copy cloning vector by sticky end cutting with restriction enzymes of KpnI,Kpn2I followed by heat-shock transformation into E.coli. Second, we performed restriction of the 8-mer plasmid by NheI and Kpn2I to extract the 8-mer. Later, the restriction was performed by SpeI and Kpn2I to obtain linearized pGSI containing 8-mer Masp1. A ligation was applied to merge 8-mer and pGSI plasmid carrying 8-mer Masp1 to achieve 16-mer Masp1 containing pGSI. Again, this plasmid was heat-shock transformed into E.coli. Following the same restriction 32-mer Masp1 containing pGSI plasmid was achieved. Finally, 32-mer Masp1 fragment was cut from pGSI cloning vector and ligated to pBbB6c low copy expression plasmid followed by electroporation into E.coli. The band size of 32-mer Masp1 gene was aligned between 3 kb and 5 kb which is an agreement with the calculated size of 32-mer Masp1 gene. Future studies should focus on the expression of Masp1 and the efficient production of this valuable recombinant protein under bioreactor conditions with cutting edge bioprocessing techniques.Master Thesis Histon Deasetilaz İnhibisyonu ve Otofaji Modülasyonunun Kolanjiokarsinoma Hücrelerine Etkisi(Abdullah Gül Üniversitesi, Fen Bilimleri Enstitüsü, 2022) Yenigül, Münevver; Yenigül, Münevver; Akçok, Emel Başak Gencer; Akçok, İsmailCholangiocarcinoma (CCA), also known as biliary tract cancer, is a heterogeneous group of malignancies formed by the differentiation of epithelial cells in the biliary tract. CCA is the second most common primary liver tumor and it has both an increasing rate and high mortality worldwide with its late diagnosis, refractory type, and aggressiveness. The effects of autophagy modulators and HDAC inhibitors in CCA are not fully known. This study is proposed a novel treatment approach with the combinational therapy of autophagy and HDAC inhibitors for CCA patients. In results obtained with alone HDACis, alone autophagy modulators, and combinations of HDACis and autophagy modulators, Nocodazole from autophagy modulators and MS-275 and Romidepsin from HDAC inhibitors showed a better synergistic effect on the TFK-1 and EGI-1 cell lines of the cholangiocarcinoma. In cell cycle analysis of the combination, was achieved arrest at the S phase and G2/M phase. In conclusion, this study highlights the important combination of HDAC inhibitors and autophagy modulators, which is a promising therapy in CCA. Keywords: Cholangiocarcinoma, HDAC inhibitors, Autophagy modulators, Combination therapyMaster Thesis SARS-CoV-2 Omikron Varyantına Özgü Tek Domainli Antikorların Protein-Protein Kenetlenmesi Yaklaşımlarıyla Tanımlanması(Abdullah Gül Üniversitesi, Fen Bilimleri Enstitüsü, 2022) İlmek, Özkan; Güner, Şerife AyazOmicron, became the dominant variant in 2022 in terms of spreading rate, has managed to evade from an immune system of patients due to its unique mutations. Single domain antibodies (sdAb) which are functionally important parts of conventional antibodies are commonly used for diagnosis and treatment. Although there are many sdAbs developed to combat coronavirus in recent years, their effectiveness against Omicron variant has not been sufficiently tested and the effect of mutations regarding neutralization level is not clear. In this study, structure modelling of 850 sdAb sequences obtained from previous studies were generated using AlphaFold 2 and effectiveness of these sdAbs against Omicron variant was tested via protein-protein docking approach. In the docking process, within a realistic approach, missing residues were completed into Spike protein PDB structures, and Spike protein homotrimer structure in closed state conformation was used. Finally, top 1000 and top 100 scores are determined as a threshold value for different protein-protein docking scoring functions such as HDOCK, PRODIGY and Bluues. sdAbs that have successful results for Omicron variant were listed. There were 4 sdAbs which exceed the threshold values after 2 different docking experiments against the Omicron variant. The scripting codes and methodological approach developed within this thesis can be used against new SARS-CoV-2 variants that may emerge in the future or other diseases.Master Thesis B Hücreli Akut Lenfoblastik Lösemi Hücre Hattında Yüzey Proteomunun Belirlenmesi(Abdullah Gül Üniversitesi / Fen Bilimleri Enstitüsü / Biyomühendislik Ana Bilim Dalı, 2022) Boyvat, Dudu; Güner, Şerife AyazB hücreli akut lenfoblastik lösemi, B lenfositlerinin aşırı ve kontrolsüz ifadesi ile karakterizedir. B-ALL, anormal sitozolik sinyal iletimi ve gen mutasyonları, anormal protein etkileşimleri ve durdurulmamış hücre döngüsü gibi moleküler anormalliklerin bir sonucu olarak ortaya çıkabilir. Bu anormallikler nedeniyle, proteomun üçte birini oluşturan yüzey proteinleri, sağlıklı hücrelere kıyasla farklı ifadeler gösterir. Bu farklılıklar günümüzde tanı ve tedavi yaklaşımlarında kullanılmaktadır. Bu çalışmada, iki farklı yüzey protein izolasyon stratejisinin karşılaştırılması ile kütle spektrometrisi tabanlı proteomik yaklaşımı ile yeni, ek olası hedef antijenleri belirlemek için CCRF-SB hücre hattının yüzey proteinlerini izole etmeyi ve tanımlamayı amaçladık. CCRF-SB hücrelerinin yüzey proteinleri, biyotinilasyon yöntemi ve N-bağlı glikoprotein zenginleştirme yöntemleri ile izole edildi. Biyotinilasyon yöntemi ile % 1 FDR oranı ile 782 protein izole ettik. Gene Ontology Cellular Component analizi, bu izole edilmiş proteinlerin 467'sinin 'Membran' ile ilişkili, 263'ünün 'Hücre Dışı Boşluk' ile ilişkili olarak tanımlamıştır. Bu izole edilmiş hücre yüzeyi proteinlerinin, HLA protein komplekslerini ve iyi bilinen CD19 yüzey işaretleyicilerini içerdiği gösterilmiştir. N-bağlı glikozillenmiş protein zenginleştirme yöntemi ile %1 FDR oranı ile tanımlanan 229 protein Gene Ontology Cellular Component 155'inin 'Membran' olarak, bu proteinlerin 132'sinin 'Hücre Dışı Boşluk' ile ilişkili olarak açıklandığını gösterdi. Her iki yöntem de birbirinden farklı proteinleri tanımlamıştır. Bu sonuç, hücre yüzeyini proteomunu haritalamak için bu iki zenginleştirme yöntemini birleştirmenin gerekli olduğunu gösterdi.